Non-human animals exhibiting psychiatric disorders, their method of obtaining and their use for drug screening
By administering vanillic acid and vanillylhydracrylic acid to mice and comparing pre- and post-administration test results, this method addresses the challenge of identifying compounds that induce invasive developmental and psychiatric disorders, and evaluates therapeutic agents' efficacy in mitigating these effects.
Patent Information
- Application Number
- FR2008005340
- Authority / Receiving Office
- FR · FR
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2008-09-29
- Publication Date
- 2025-03-28
- Estimated Expiration
- 2028-09-29
AI Technical Summary
Current methods lack effectiveness in identifying and addressing invasive developmental disorders and psychiatric disorders induced by certain compounds in non-human mammals, such as mice.
The use of non-human mammals, specifically mice, to administer compounds like vanillic acid and vanillylhydracrylic acid, and subsequently assess the development of disorders through comparative testing before and after administration, allowing for the screening of therapeutic agents that may prevent or reduce these disorders.
This approach enables the determination of whether a compound induces disorders and allows for the evaluation of therapeutic agents' effectiveness in preventing or reducing these disorders, providing a method for screening potential treatments.
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Abstract
Description
Said tests or analyses may be carried out before administration of the compound inducing pervasive developmental disorders and / or psychiatric disorders; thus the values obtained in the non-human mammal before administration serve as internal references. The reference may also be the values obtained in the aforementioned tests and analyses on another healthy mammal of the same species; these are then external references. By comparing the differences between the values obtained during the tests and analyses carried out on the above-mentioned non-human mammals before and after administration of the above-mentioned compound, it is possible to determine whether the above-mentioned compound administered can induce the above-mentioned disorders and / or disorders. According to an advantageous embodiment, in the method of the invention, the non-human mammal is chosen from canids, felids, mustelids, suids, primates, rodents, preferentially from rat, hamster, gerbil, chinchilla, guinea pig, rabbit, monkey, ferret, pig, dog, or cat, and is in particular a mouse. According to another advantageous embodiment, in the method of the invention the compound is administered to the non-human mammal by digestive, cutaneous, rectal route, respiratory, for example by inhalation, instillation, or nebulization of a spray on the mucous membranes, preferably by parenteral route, for example by intravenous, intra-arterial, intrathecal, intraperitoneal, epidural, subcutaneous, intradermal or intramuscular injection, According to an advantageous embodiment of the invention, the quantity of compound administered to the non-human mammal is from 0.01 mg / kg to 100 mg / kg, in particular 1 mg / kg to 50 mg / kg, the quantity of compound administered preferably being 10 mg / kg. Depending on the case, the amount of compound administered may be from 1 mg / kg to 50 mg / kg or from 20 mg / kg to 100 mg / kg, In the case of prolonged exposure, the doses may be from 0.01 mg / kg to 10 mg / kg, in particular 0.1 mg / kg to 5 mg / kg, the quantity of compound administered preferably being 1 mg / kg. The method of the invention relates in particular to obtaining a mouse, presenting pervasive developmental disorders and / or psychiatric disorders, which method optionally comprises a step of comparison between: the mouse obtained following the administration of vanillic acid and the mouse before administration of vanillic acid, or a healthy mouse in which no compound, in particular vanillic acid, is administered. According to another embodiment, the method of the invention relates in particular to obtaining a mouse, presenting pervasive developmental disorders and / or psychiatric disorders, which method comprises a step of administering to the mouse 0.01 mg / kg to 100 mg / kg, in particular 5 mg / kg to 50 mg / kg, preferably 10 mg / kg of vanillylhydracrylic acid, and optionally a step of comparison between: the mouse obtained following the administration of vanillylhydracrylic acid, and the mouse before administration of vanillylhydracrylic acid. or a healthy mouse in which no compound, in particular vanillylhydracrylic acid, is administered. According to another advantageous embodiment, the method of the invention relates in particular to obtaining a mouse, presenting pervasive developmental disorders and / or psychiatric disorders, which method comprises a step of administering to the mouse 0.01 mg / kg to 100 mg / kg, in particular 10 mg / kg to 50 mg / kg, preferably 20 mg / kg of a mixture in proportions preferably ranging from 1 / 10 to 10 / 1 of vanillic acid and vanillylhydracrylic acid, in particular at a rate of 10 mg / kg of vanillic acid and 10 mg / kg of vanillylhydracrylic acid. and possibly a comparison step between: the mouse obtained after administration of the mixture of vanillic acid and vanillylhydracrylic acid, and the mouse before administration of the mixture of vanillic acid and vanillylhydracrylic acid, or with a healthy mouse in which no compound, in particular a mixture of vanillic and vanillylhydracrylic acids, is administered. The invention also relates to the use of a non-human mammal exhibiting pervasive developmental disorders and / or psychiatric disorders, for screening therapeutic agents capable of preventing, reducing or substantially reversing the pervasive developmental disorders and / or psychiatric disorders, in which has been administered at least one compound corresponding to the following formula (I): Ra in which: * n = 0 or 1, * Ra represents -CH2OH, -COOH, or -NR1R2, with RI and R2 representing, independently of each other, a hydrogen atom or an alkyl group of 1 to 3 carbon atoms, * Rb represents an alkyl group of 1 to 3 carbon atoms, preferably a -CH3 group, * Z represents a hydrocarbon chain of 1 to 3 carbon atoms, in particular of 1 or 2 carbon atoms, where appropriate substituted by an OH group, said chain comprising where appropriate an -NH- and / or -CO- group, * said compounds being, where appropriate, in the form of salts or, when there is the presence of at least one asymmetric carbon, in the form of isomers alone or in a racemic mixture, said compound being responsible for the above-mentioned disorders and / or disorders, and a therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, and possibly including a comparison step between: the non-human mammal obtained following the administration of the above-mentioned compound and therapeutic agent. * the aforesaid non-human mammal to which the aforesaid compound has been administered, but the aforesaid therapeutic agent has not been administered, or * another healthy non-human mammal of the same species as that to which the above compound was administered, to which the above compound was administered, but the above therapeutic agent was not administered. A non-human mammal, to which at least one compound inducing pervasive developmental disorders and / or psychiatric disorders has been administered, is treated with a therapeutic agent whose effect on the aforementioned pervasive developmental disorders and / or psychiatric disorders is to be evaluated. In order to judge the efficacy of this therapeutic agent, behavioral tests, and / or tests on biological samples, and / or samples of biological material are carried out on the aforementioned non-human mammal. The results obtained during the aforementioned tests and / or samples are compared with the results obtained for the same tests and / or samples obtained on a non-human mammal serving as a reference. The above-mentioned reference non-human mammal may in particular be the same non-human mammal which underwent the administration of the above-mentioned compound inducing the above-mentioned disorders and / or disorders before administration of the above-mentioned therapeutic agent, this being a internal reference. This may be another non-human mammal of the same species, having undergone administration of the compound inducing the aforementioned disorders and / or problems; this is then an external reference. The differences observed during the above tests and / or samples, between the non-human mammal treated with the above compound and the above therapeutic agent, and the non-human mammal serving as a reference, make it possible to determine whether the therapeutic agent has an effect on the behavioral disorders induced by the compound. Screening refers to the identification of molecules with new, biologically active properties. Screening refers to a set of techniques that allow the biological properties of a large number of molecules to be verified using standardized tests applicable to a large quantity of samples. The term "therapeutic agents" refers to all compounds capable of combating diseases, restoring and preserving health; such as, for example, medicines and vaccines. According to an advantageous embodiment, the invention relates to the use of a non-human mammal, in particular a mouse, exhibiting pervasive developmental disorders and / or psychiatric disorders, for screening therapeutic agents capable of preventing, reducing or substantially canceling pervasive developmental disorders and / or psychiatric disorders, in which non-human mammal, in particular a mouse, has been administered from 0.01 mg / kg to 100 mg / kg, in particular 5 mg / kg to 50 mg / kg, preferably 10 mg / kg to 20 mg / kg of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids in proportions preferably ranging from 1 / 10 to 10 / 1, said compound being responsible for the above-mentioned troubles and / or disorders, and a therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, and possibly including a comparison step between: the non-human mammal, in particular a mouse, obtained following the administration of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids, and the above-mentioned therapeutic agent, and * the aforesaid non-human mammal, in particular a mouse, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids has been administered, but the aforesaid therapeutic agent has not been administered, or * another healthy non-human mammal, in particular a mouse, of the same species as the one to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, but the above-mentioned therapeutic agent was not administered. The present invention relates to a method for screening for therapeutic agents capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders from a non-human mammal to which has been administered: - at least one compound of the following formula (I): Ra zi Jn CD HO ORb in which: * n = 0 or 1, * Ra represents -CH2OH, -COOH, or -NR1R2, with RI and R2 representing, independently of each other, a hydrogen atom or an alkyl group of 1 to 3 carbon atoms, * Rb represents an alkyl group of 1 to 3 carbon atoms, preferably a -CH3 group, * Z represents a hydrocarbon chain of 1 to 3 carbon atoms, in particular of 1 or 2 carbon atoms, where appropriate substituted by a OH group, said chain optionally comprising a -NH- and / or -CO- group, * said compounds being, where appropriate, in the form of salts or, when there is the presence of at least one asymmetric carbon, in the form of isomers alone or in a racemic mixture, said compound being responsible for the above-mentioned disorders and / or disorders, and - at least one therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, including: at least one of the steps chosen from: * a step of blood and / or urine dosage, in vitro, of said compound or one of its metabolites from a sample originating from the above-mentioned non-human mammal in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a step of behavioral study of the above-mentioned non-human mammal in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a tissue and / or cellular study carried out on organs or tissues of the above-mentioned non-human mammal in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a whole animal study using imaging techniques. and possibly a comparison step between: the non-human mammal to which the above-mentioned compound and therapeutic agent have been administered, and * the aforesaid non-human mammal to which the compound has been administered, but the therapeutic agent has not been administered, or * another healthy non-human mammal of the same species as that to which the above compound was administered, to which the above compound was administered, but the above therapeutic agent was not administered. “An assay step” means any series of measurements carried out on fluid samples from the aforementioned non-human mammal. “Sample from the aforementioned non-human mammal” means a quantity of liquid, for example blood, urine, cerebrospinal fluid, saliva, taken or collected from the aforementioned non-human mammal. By "a behavioral study stage" is meant any series of measurements carried out on the aforementioned non-human mammal, including a phase of evaluation and rating of a set of reactions observable in the aforementioned non-human mammal placed in its living environment, or in any other environment, and in given circumstances. A "tissue study" means an observation and analysis of a set of tissues in order to characterize a modification or a difference between the observed tissue and a tissue of the same type from a healthy reference sample. A "cellular study" means an observation and analysis of a set of cells in order to characterize a modification or a difference between the observed cells and cells of the same type from a healthy reference sample. "Whole animal imaging study" means an observation or analysis of a whole animal using imaging techniques in order to characterize a modification or difference between a whole organism, or an organ of this organism, and another organism serving as a reference, or an organ of this other organism serving as a reference. Within the framework of the above-mentioned tissue studies, cellular studies and whole animal studies, it is possible to carry out studies of proliferation, differentiation, migration, synaptogenesis, remodeling, receptorology, enzymology, immunocytochemistry, immunohistochemistry, imaging (by electroencephalography, by computed tomography, by nuclear magnetic resonance, by single-photon emission tomography, by posPon emission tomography, by radiography, by FRET, by scanner, ...), stereotaxy, proteomics, transcriptomics, interactomics, metabolomics, neurotransmitters, cellular and molecular pharmacology, intracellular messengers, transcription factors, molecular biology, electrophysiology, pro- or anti-apoptotic effects, synaptic plasticity, efficiency and strength of synaptic transmission or even physical studies (microscopic, ultrasonographic, thermographic, magnetoencephalographic, scintigraphic, etc.) or biochemical studies (electrophoresis, Western blotting, chromatography, etc.). All these techniques are classic and known to those skilled in the art. By "organs" we mean a set of tissues contributing to the performance of a physiological function. By "tissues" we mean a set of cells that are not necessarily identical but of the same origin, grouped together in a functional set, that is to say contributing to the same function. According to an advantageous embodiment for the screening method of the invention, use is made of a non-human mammal to which the following has been administered: at least one compound of the following formula (I): Ra in which: * n = 0 or 1, * Ra represents -CH2OH, -COOH, or -NR1R2, with RI and R2 representing, independently of each other, a hydrogen atom or an alkyl group of 1 to 3 carbon atoms, * Rb represents an alkyl group of 1 to 3 carbon atoms, preferably a -CH3 group, * Z represents a hydrocarbon chain of 1 to 3 carbon atoms, in particular of 1 or 2 carbon atoms, where appropriate substituted by an OH group, said chain comprising where appropriate an -NH- and / or -CO- group, * said compounds being, where appropriate, in the form of salts or, when there is the presence of at least one asymmetric carbon, in the form of isomers alone or in a racemic mixture, said compound being responsible for the above-mentioned disorders and / or disorders, and including: the administration to the above-mentioned non-human mammal of at least one therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, and at least one of the steps chosen from: * a step of blood and / or urine dosage, in vitro, of said compound or one of its metabolites from a sample originating from the above-mentioned non-human mammal in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a step of behavioral study of the above-mentioned non-human mammal in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a tissue and / or cellular study carried out on organs or tissues of the above-mentioned non-human mammal in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a whole animal study using imaging techniques. and possibly a comparison step between: the non-human mammal to which the above compound and the above therapeutic agent have been administered, and * the aforesaid non-human mammal to which the compound has been administered, but the therapeutic agent has not been administered, or * another healthy non-human mammal of the same species as the one to which the above-mentioned compound was administered, to which the above-mentioned compound was administered, but the above-mentioned therapeutic agent was not administered. The above compound and the above therapeutic agent may advantageously be administered at the same time or at different times. The time interval between the two administrations can vary from 1 second to several weeks, in particular from 1 minute to 1 week, preferably 24 hours. The time interval between the last of the two administrations and the dosage step, and / or tissue study, and / or cellular study, and / or may vary from 1 second to several weeks, in particular from 1 minute to 1 week, preferably 24 hours. According to an advantageous embodiment for the screening method of the invention, use is made of: the administration to a non-human mammal of at least one compound of the following formula (I): Ra in which: * n = 0 or 1, * Ra represents -CH2OH, -COOH, or -NR1R2, with RI and R2 representing, independently of each other, a hydrogen atom or an alkyl group of 1 to 3 carbon atoms, * Rb represents an alkyl group of 1 to 3 carbon atoms, preferably a -CH3 group, * Z represents a hydrocarbon chain of 1 to 3 carbon atoms, in particular of 1 or 2 carbon atoms, where appropriate substituted by an OH group, said chain comprising where appropriate an -NH- and / or -CO- group, * said compounds being, where appropriate, in the form of salts or, when there is the presence of at least one asymmetric carbon, in the form of isomers alone or in a racemic mixture, 25 said compound being responsible for the above-mentioned disorders and / or disorders, and the administration to the above-mentioned non-human mammal of at least one therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, and at least one of the steps chosen from: * a step of blood and / or urine dosage, in vitro, of said compound or one of its metabolites from a sample originating from the above-mentioned non-human mammal in which the above-mentioned compound and therapeutic agent are administered, * a step of behavioral study of the above-mentioned non-human mammal in which the above-mentioned compound and therapeutic agent are administered, * a tissue and / or cellular study carried out on organs or tissues of the above-mentioned non-human mammal in which the above-mentioned compound and therapeutic agent are administered, * a whole animal study using imaging techniques. and possibly a comparison step between: the non-human mammal to which the above-mentioned compound and therapeutic agent have been administered, and * the aforesaid non-human mammal to which the compound has been administered, but the therapeutic agent has not been administered, or * another healthy non-human mammal of the same species as that to which the above compound was administered, to which the above compound was administered, but the above therapeutic agent was not administered. According to an advantageous embodiment in the screening method of the invention, it was administered to a non-human mammal, in particular to a mouse: from 0.01 mg / kg to 100 mg / kg, in particular 5 mg / kg to 50 mg / kg, preferably 10 mg / kg to 20 mg / kg of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids in proportions ranging from 1 / 10 to 10 / 1, in particular at a rate of 10 mg / kg of vanillic acid and 10 mg / kg of vanillylhydracrylic acid, said compound or mixture of compounds being responsible for the above-mentioned troubles and / or disorders, and at least one therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, which process comprises at least one of the steps chosen from: * a step of blood and / or urine dosage, in vitro, of said compound or one of its metabolites from a sample originating from the above-mentioned non-human mammal, in particular a mouse, in which the above-mentioned compound and therapeutic agent are administered, * a step of behavioral study of the above-mentioned non-human mammal, in particular a mouse, in which the above-mentioned compound and therapeutic agent are administered, * a tissue and / or cellular study carried out on organs or tissues of the above-mentioned non-human mammal, in particular a mouse, in which the above-mentioned compound and therapeutic agent are administered, * a whole animal study using imaging techniques. and possibly a comparison step between: the non-human mammal, in particular a mouse, obtained following the administration of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids, and the above-mentioned therapeutic agent, and * the aforesaid non-human mammal, in particular a mouse, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids has been administered, but the aforesaid therapeutic agent has not been administered, or * another healthy non-human mammal, in particular a mouse, of the same species as the one to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, but the above-mentioned therapeutic agent was not administered. According to another advantageous embodiment in the screening method of the invention, it was administered to a non-human mammal, in particular to a mouse: from 0.01 mg / kg to 100 mg / kg, in particular 5 mg / kg to 50 mg / kg, preferably 10 mg / kg to 20 mg / kg of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids in proportions ranging from 1 / 10 to 10 / 1, in particular at a rate of 10 mg / kg of vanillic acid and 10 mg / kg of vanillylhydracrylic acid, said compound or mixture of compounds being responsible for the above-mentioned troubles and / or disorders, and which method comprises: the injection into the above-mentioned non-human mammal, in particular a mouse, of at least one therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, and at least one of the steps chosen from: * a step of blood and / or urine dosage, in vitro, of said compound or one of its metabolites from a sample originating from the above-mentioned non-human mammal, in particular a mouse, in which the above-mentioned compound and therapeutic agent are administered, * a step of behavioral study of the above-mentioned non-human mammal, in particular a mouse, in which the above-mentioned compound and therapeutic agent are administered, * a tissue and / or cellular study carried out on organs or tissues of the above-mentioned non-human mammal, in particular a mouse, in which the above-mentioned compound and therapeutic agent are administered, * a whole animal study using imaging techniques. and possibly a comparison step between: the non-human mammal, in particular a mouse, obtained following the administration of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids, and the above-mentioned therapeutic agent, and * the aforesaid non-human mammal, in particular a mouse, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids has been administered, but the aforesaid therapeutic agent has not been administered, or * another healthy non-human mammal, in particular a mouse, of the same species as the one to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, but the above-mentioned therapeutic agent was not administered. According to another advantageous embodiment in the screening method of the invention, the method comprises: the administration of 0.01 mg / kg to 100 mg / kg, in particular 5 mg / kg to 50 mg / kg, preferably 10 mg / kg to 20 mg / kg of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids in proportions ranging from 1 / 10 to 10 / 1, in particular at a rate of 10 mg / kg of vanillic acid and 10 mg / kg of vanillylhydracrylic acid, said compound or mixture of compounds being responsible for the above-mentioned disorders and / or disorders, to the above-mentioned non-human mammal, in particular a mouse, and the injection into the above-mentioned non-human mammal, in particular a mouse, of at least one therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, and at least one of the steps chosen from: * a step of blood and / or urine dosage, in vitro, of said compound or one of its metabolites from a sample originating from the above-mentioned non-human mammal, in particular a mouse, in which the above-mentioned compound and therapeutic agent are administered. * a step of behavioral study of the above-mentioned non-human mammal in which the above-mentioned compound and therapeutic agent are administered, * a tissue and / or cellular study carried out on organs or tissues of the above-mentioned non-human mammal in which the above-mentioned compound and therapeutic agent are administered, * a whole animal study using imaging techniques. and possibly a comparison step between: the non-human mammal, in particular a mouse, obtained following the administration of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids, and the above-mentioned therapeutic agent, and * the aforesaid non-human mammal, in particular a mouse, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids has been administered, but the aforesaid therapeutic agent has not been administered, or * another healthy non-human mammal, in particular a mouse, of the same species as the one to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, but the above-mentioned therapeutic agent was not administered. According to another advantageous embodiment in the screening method of the invention, it was administered to a non-human mammal, in particular to a mouse: from 0.01 mg / kg to 100 mg / kg, in particular 5 mg / kg to 50 mg / kg, preferably 10 mg / kg to 20 mg / kg of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids in proportions ranging from 1 / 10 to 10 / 1, in particular at a rate of 10 mg / kg of vanillic acid and 10 mg / kg of vanillylhydracrylic acid, said compound or mixture of compounds being responsible for the above-mentioned troubles and / or disorders, and at least one therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, said method comprises: a step of behavioral study of the above-mentioned non-human mammal, in particular a mouse, in which the above-mentioned compound and therapeutic agent are administered, and possibly a comparison step between: the non-human mammal, in particular a mouse, obtained following the administration of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids, and the above-mentioned therapeutic agent, and * the aforesaid non-human mammal, in particular a mouse, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids has been administered, but the aforesaid therapeutic agent has not been administered, or * another healthy non-human mammal, in particular a mouse, of the same species as the one to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, but the above-mentioned therapeutic agent was not administered, According to another embodiment, the screening method of the invention relates to the evaluation of a method capable of preventing, reducing or substantially canceling pervasive developmental disorders and / or psychiatric disorders, the method comprises: the administration to a non-human mammal, in particular to a mouse, of at least one compound corresponding to the following formula (I): Ra in which: * n ;= 0 or 1, * Ra represents -CH2OH, -COOH, or -NR1R2, with RI and R2 representing, independently of each other, a hydrogen atom or an alkyl group of 1 to 3 carbon atoms, * Rb represents an alkyl group of 1 to 3 carbon atoms, preferably a -CH3 group, * Z represents a hydrocarbon chain of 1 to 3 carbon atoms, in particular of 1 or 2 carbon atoms, where appropriate substituted by an OH group, said chain comprising where appropriate an -NH- and / or -CO- group, * said compounds being, where appropriate, in the form of salts or, when there is the presence of at least one asymmetric carbon, in the form of isomers alone or in a racemic mixture, said compound being responsible for the above-mentioned disorders and / or disorders, and the application of a method likely to prevent, reduce or substantially cancel pervasive developmental disorders and / or psychiatric disorders, said method optionally comprises a step of comparison between: the non-human mammal obtained following administration of the compound and application of the method, and * the aforesaid non-human mammal to which the compound has been administered, but no method has been applied, or * another healthy non-human mammal of the same species as the one to which the compound was administered and the method applied, to which the compound was administered, but no method was applied. By "evaluation" we mean any action aimed at appreciating, estimating, the value or technical effectiveness of a method. By "method capable of preventing, reducing or substantially cancelling pervasive developmental disorders and / or psychiatric disorders" is meant any method, administration of compounds, physical or mental stimulation process, special diet, vaccination, making it possible to prevent, reduce or eliminate the discomfort, suffering or physical or psychological disorders caused by pervasive developmental disorders and / or psychiatric disorders. Description of figures Figure 1. Open field test This Tuckey diagram depicts six boxes paired together in three vertical series along the x-axis. The y-axis represents the number of movements recorded per mouse during an open field test. Each series of boxes includes a light box representing the so-called control mice, and a dark box representing the mice injected with the AV (vanillic acid) + VH (vanillylhydracrylic acid) mixture. The first series of 2 boxes marked D1 represents the results on day 1, the second series of boxes marked D2 represents the results on day 2, the third series of boxes marked D3 represents the results on day 3. The three days are consecutive. Each box represents one interquartile range (+ or - one quartile from the median value) for the measurement represented, the median value is indicated by a horizontal line inside the box. The thin extensions at the ends of each box represent the 1st and 9th deciles. The points above and below each box represent the maximum values. Differences are significant for p<0.05 (*). Figure 2. Movements in the light compartment during the seat preference test This Tuckey diagram depicts four vertical boxes along the abscissa axis. The y-axis represents the number of recorded movements of the mice into the clear compartment during a place preference test. The first box marked control represents the results for so-called control mice (no product administered), the second box marked AV represents the results for so-called AV mice (administration of vanillic acid). The third box marked VH represents the results for so-called VH mice (administration of vanillylhydracrylic acid). The fourth box marked AV+VH represents the results for so-called AV+VH mice (administration of vanillic acid and acid). vani 1 ly Ihydracry 1 ique). Each box represents one interquartile range (+ or - one quartile from the median value) for the measurement represented, the median value is indicated by a horizontal line inside the box. The thin extensions at the ends of each box represent the 1st and 9th deciles. The points that may appear above the boxes represent the maximum values. When this point is not shown, it means that the decile point is superimposed on the point of the maximum value. It is noted that the mice administered the AV compounds and the AV+VH mixture move less in the clear compartment than the so-called control mice. Figure 3. Total movements of mice in the place preference test This Tuckey diagram depicts four vertical boxes along the x-axis. The y-axis represents the number of movements, per mouse, recorded in the two light and dark compartments during a place preference test. The first box marked control represents the results for so-called control mice (no product administered), the second box marked AV represents the results for so-called AV mice (administration of vanillic acid). The third box marked VH represents the results for so-called VH mice (administration of vanillylhydracrylic acid). The fourth box marked AV+VH represents the results for so-called AV+VH mice (administration of vanillic acid and vanillylhydracrylic acid). Each box represents one interquartile range (+ or - one quartile from the median value) for the measurement represented, the median value is indicated by a horizontal line inside the box. The thin extensions at the ends of each box represent the 1st and 9th deciles. The points that may appear above and below the boxes represent the maximum values. When this point is not shown, it means that the decile point is superimposed on the point of the maximum value. It is noted that the mice administered the AV, VH compounds and the AV+VH mixture have reduced exploratory activity compared to the so-called control mice. Figure 4. Time spent by mice in the clear compartment during the place preference test. This Tuckey diagram depicts four vertical boxes along the abscissa axis. The y-axis represents the times (in seconds) of presence recorded in the clear compartment during a place preference test. The first box labeled control represents the results for so-called control mice (no product administered), the second box labeled AV represents the results for so-called AV mice (administration of vanillic acid). The third box labeled VH represents the results for so-called VH mice (administration of vanillylhydracrylic acid). The fourth box labeled AV+VH represents the results for so-called AV+VH mice (administration of vanillic acid and vanillylhydracrylic acid). Each box represents one interquartile range (+ or - one quartile from the median value) for the measurement represented, the median value is indicated by a horizontal line inside the box. The thin extensions at the ends of each box represent the 1st and 9th deciles. The points that may appear above and below the boxes represent the maximum values. When this point is not shown, it means that the decile point is superimposed on the point of the maximum value. It is noted that mice administered the AV compounds and the AV+VH mixture spend less time in the clear compartment than the so-called control mice. Figure 5. Head exit time of mice during the emergence test. This Tuckey diagram depicts four vertical boxes along the x-axis. The y-axis represents the times (in seconds) for the mice's heads to emerge from the dark enclosure, recorded during the emergence test. The first box, labeled control, represents the results for so-called control mice (no product administered), the second box, labeled AV, represents the results for so-called AV mice (administration of vanillic acid). The third box, labeled VH, represents the results for so-called VH mice. (administration of vanillylhydracrylic acid). The fourth box marked AV+VH represents the results for mice called AV+VH (administration of vanillic acid and vanillylhydracrylic acid). Each box represents one interquartile range (+ or - one quartile from the median value) for the measurement represented, the median value is indicated by a horizontal line inside the box. The thin extensions at the ends of each box represent the 1st and 9th deciles. The points that may appear above and below the boxes represent the maximum values. When this point is not shown, it means that the decile point is superimposed on the point of the maximum value. Figure 6. Exit time of both front paws of mice during the emergence test This Tuckey diagram depicts four vertical boxes along the x-axis. The y-axis represents the times (in seconds) for the mice's two front paws to exit the dark enclosure, recorded during the emergence test. The first box, labeled control, represents the results for control mice (no product administered), while the second box, labeled AV, represents the results for AV mice (vanillic acid administered). The third box, labeled VH, represents the results for VH mice (vanillylhydracrylic acid administered). The fourth box, labeled AV+VH, represents the results for AV+VH mice (vanillic acid and vanillylhydracrylic acid administered). Each box represents one interquartile range (+ or - one quartile from the median value) for the measurement represented, the median value is indicated by a horizontal line inside the box. The thin extensions at the ends of each box represent the 1st and 9th deciles. The points that may appear above and below the boxes represent the maximum values. When this point is not shown, it means that the decile point is superimposed on the point of the maximum value. It is noted that the mice administered the AV+VH mixture took longer to partially exit the enclosure than the so-called control mice. Figure 7. Time taken for mice to fully exit the dark enclosure during the emergence test This Tuckey diagram depicts four vertical boxes along the x-axis. The y-axis represents the times (in seconds) for the mice to fully exit the dark enclosure recorded during the emergence test. The first box, labeled control, represents the results for control mice (no product administered), the second box, labeled AV, represents the results for AV mice (vanillic acid administration). The third box, labeled VH, represents the results for VH mice (vanillylhydracrylic acid administration). The fourth box (horizontal line at the top of the graph), labeled AV+VH, represents the results for AV+VH mice (vanillic acid and vanillylhydracrylic acid administration). Each box represents one interquartile range (+ or - one quartile from the median value) for the measurement represented, the median value is indicated by a horizontal line inside the box. The thin extensions at the ends of each box represent the 1st and 9th deciles. The points that may appear above and below the boxes represent the maximum values. When this point is not shown, it means that the decile point is superimposed on the point of the maximum value. It is noted that mice administered the AV and VH compounds emerge very late from the dark enclosure. Mice administered the AV+VH mixture will not emerge from the dark enclosure. Figure 8. Delay of contact of mice with the novel object during the novel object test This Tuckey diagram depicts four vertical boxes along the abscissa axis. The y-axis represents the time (in seconds) of contact of the mice with the novel object, recorded during the novel object test. The first box marked control represents the results for so-called control mice (no product administered), the second box marked AV represents the results for mice called AV (administration of vanillic acid). The third box marked VH represents the results for mice called VH (administration of vanillylhydracrylic acid). The fourth box marked AV+VH represents the results for mice called AV+VH (administration of vanillic acid and vanillylhydracrylic acid). Each box represents one interquartile range (+ or - one quartile from the median value) for the measurement represented, the median value is indicated by a horizontal line inside the box. The thin extensions at the ends of each box represent the 1st and 9th deciles. The points that may appear above and below the boxes represent the maximum values. When this point is not shown, it means that the decile point is superimposed on the point of the maximum value. It is noted that the results are not significantly different regardless of the treatment. Figure 9. Number of contacts of mice with the novel object during the novel object test This Tuckey diagram depicts four vertical boxes along the x-axis. The y-axis represents the number of times the mice contacted the novel object, recorded during the novel object test. The first box, labeled control, represents the results for control mice (no product administered), and the second box, labeled AV, represents the results for AV mice (vanillic acid administered). The third box, labeled VH, represents the results for VH mice (vanillylhydracrylic acid administered). The fourth box, labeled AV+VH, represents the results for AV+VH mice (vanillic acid and vanillylhydracrylic acid administered). Each box represents one interquartile range (+ or - one quartile from the median value) for the measurement represented, the median value is indicated by a horizontal line inside the box. The thin extensions at the ends of each box represent the 1st and 9th deciles. The points that may appear above and below the boxes represent the maximum values. When this point is not shown, it means that the decile point is superimposed on the point of the maximum value. It is noted that the number of contacts is very reduced in mice to which the AV, VH compounds or even the AV+VH mixture were administered. Figure 10. Number of contacts of mice with a novel conspecific during the social interaction test. This Tuckey diagram depicts four vertical boxes along the x-axis. The y-axis represents the number of contacts the mice made with a new conspecific, recorded during the social interaction test. The first box, labeled control, represents the results for control mice (no product administered), the second box, labeled AV, represents the results for AV mice (administration of vanillic acid). The third box, labeled VH, represents the results for VH mice (administration of vanillylhydracrylic acid). The fourth box, labeled AV+VH, represents the results for AV+VH mice (administration of vanillic acid and vanillylhydracrylic acid). Each box represents one interquartile range (+ or - one quartile from the median value) for the measurement represented, the median value is indicated by a horizontal line inside the box. The thin extensions at the ends of each box represent the 1st and 9th deciles. The points that may appear above and below the boxes represent the maximum values. When this point is not shown, it means that the decile point is superimposed on the point of the maximum value. It is noted that the number of contacts is very reduced in mice to which the AV, VH compounds or even the AV+VH mixture were administered. Figure 11. Contact time of mice with a new conspecific during the social interaction test This Tuckey diagram depicts four vertical boxes along the x-axis. The y-axis represents the time taken for mice to contact a new conspecific, recorded during the social interaction test. The first box, labeled control 5, represents the results for control mice (no product administered), the second box, labeled AV, represents the results for AV mice (administration of vanillic acid). The third box, labeled VH, represents the results for VH mice (administration of vanillylhydracrylic acid). The fourth box, labeled AV+VH, represents the results for AV+VH mice (administration of vanillic acid and vanillylhydracrylic acid). Each box represents one interquartile range (+ or - one quartile from the median value) for the measurement represented, the median value is indicated by a horizontal line inside the box. The thin extensions at the ends of each box represent the 1st and 9th 15 deciles. The points that may appear above and below the boxes represent the maximum values. When this point is not shown, it means that the decile point is superimposed on the point of the maximum value. 20 It is noted that the number of contacts is significantly increased in VH mice. Experimental part On the animal (whole or on the head alone), on the brain (whole or on isolated parts, either freshly obtained or in organotypic culture), on tissue sections, on isolated neurons or on neurons in cell culture, it is possible to carry out studies of proliferation, differentiation, migration, synaptogenesis, remodeling, receptorology, enzymology, immunocytochemistry, immunohistochemistry, imaging (by electroencephalography, by computed tomography, by nuclear magnetic resonance, by single-photon emission tomography, by positron emission tomography, by radiography, by FRET, by scanner, ...), stereotaxy, proteomics, transcriptomics, interactomics, metabolomics, neurotransmitters, cellular and molecular pharmacology, intracellular messengers, transcription factors, molecular biology, electrophysiology, pro- or anti-apoptotic effects, synaptic plasticity, efficiency and strength of synaptic transmission or even physical studies (microscopic, ultrasonographic, thermographic, magnetoencephalographic, scintigraphic, ...), biochemical (electrophoresis, Western blotting, chromatography, ...) or even behavioral. Several examples illustrate these studies. They will be carried out mainly on isolated cells in culture, on tissue sections or even on the whole animal. It is understood that the techniques and examples described below are described in order to facilitate the implementation of the invention by those skilled in the art. The techniques indicated should obviously in no case be considered as a limitation to the present invention, insofar as all variants of said techniques are equally applicable to the present invention. I Biological tests 1. Biological material 1.1. Primary culture of neurons. The hippocampus is a key component of the limbic system and memory processes. It has been suggested that this brain region may be involved in autism. All procedures and experimental protocols performed on animals follow the recommendations of the Animal Ethics Committee. Dissected hippocampi are dissociated with papain solution (Worthington) for 45 min at 37°C with gentle agitation. Alternatively, dissociation can be carried out using 0.025% (w / v) trypsin solution with gentle agitation. The resulting cell suspension is centrifuged and the pellet resuspended in culture medium (e.g., Neurobasal-A plus B27) and placed in culture flasks coated with a matrix composed of poly-D-lysine / laminin. The substrate can optionally be poly-L-Lysine and the medium can contain different concentrations of K+. Eventually, a solution of 0.05% (w / v) DNase can be used beforehand to catabolize DNA from dead cells. Neurons are cultured in a 5% CO2, 36°C incubator. Optionally, the next day, cytosine {alpha}-D-arabinofuranoside (AraC) is added (at 5 pM) to prevent glial cell proliferation. The culture medium is changed every 4 days. 1.2. Organotypic tissue culture. Hippocampi (or other brain region) are dissected from anesthetized mice that have been treated or not with a compound described in patent FR2899973. They are then cut transversely into thick slices of approximately 400 μm using a microtome. The sections are then deposited on a sterile Millicell-CM membrane (Millipore) and cultured in a CO2 (5%) incubator at a temperature of 36°C. A culture medium (Neurobasal-A plus B27; Invitrogen, Paris) containing 20% horse serum is used for the first 4 days. The serum concentration is then gradually decreased to reach 5% in 48 hours. Then, after a 24-hour incubation period in serum-free medium, the sections are used either for electrophysiological measurements, or for immunocytochemistry, or for isotopic labeling. 2. Techniques 2.1. Immunocytochemical measurements. Sections or cultured cells that have (or have not) been incubated with the compounds mentioned in patent FR2899973 are rinsed with PBS (Phosphate Buffered Saline) buffer and then fixed with a 4% paraformaldehyde solution containing 4% sucrose. After several rinses with PBS and then with PBS containing 10 mM NH4Cl, the sections or cells are incubated for 1 h with a blocking / permeabilization solution (PBS containing 0.5% bovine serum and 0.1% Triton X-100). Then the sections or cells are exposed to a solution containing antibodies diluted in the blocking / permeabilization solution. These antibodies are directed against different membrane or intracellular proteins or receptors. These receptors are neurotransmitter receptors or receptors of the TRCP (Transducin Repeat Containing Protein) family.The sections or cells are then incubated with a solution containing a second labeled antibody. This labeling is either fluorescent (Rhodamine, Texas Red, FITC, etc.) or enzymatic (alkaline phosphatase, peroxidase, etc.) or it can be a biotin labeling which will be revealed by an avidin or streptavidin conjugate. 2.2. RT-PCR. Tissue sections or aliquots of cultured cells are analyzed by RT-PCR (Reverse Transcription Polymerization Chain Reaction) using commercial kits and standard molecular biology techniques known to those skilled in the art (Molecular cloning: a laboratory manual. by T. Maniatis, EF Fritsch, J. Sambrook (1982) Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press). The expression of neurotransmitter receptors or receptors of the TRCP family can, for example, be investigated. 2.3. Cell viability measurements. The cultured cells are incubated with variable concentrations and / or variable times with one or more compounds cited in patent FR2899973 in combination or not with antagonists or other pharmacological effectors and compared with untreated control cells. At the end of the treatment, cell viability is evaluated using conventional cell viability tests known to those skilled in the art (Basic cell culture protocols, (Methods in molecular biology), (3rd Ed.); JW Pollard and JM Walker, Eds, Humana Press). 2.4. Determination of variations in intracellular calcium concentrations. This measurement involves fluorescent markers such as Fluo, Indo or Fura (Handbook of Fluorescent Probes and Research Products, Molecular Probes, RP Haugland). The principle is an incubation of cells with a permeant fluorescent marker in a balanced buffer possibly containing Pluronic which facilitates the incorporation of fluorescent probes. After the incubation period (usually 30 min), the cells are rinsed with PBS and exposed to effectors in culture medium or in saline solution, at 37°C. Fluorescence intensity variations are visualized using a camera and a fluorescence microscope at the excitation and emission wavelengths characteristic of the fluorescent probes used. The effectors used can be either neurotransmitters, related molecules, the compounds described in patent FR2899973 or even potential antagonists.This variation in fluorescence intensity is converted into intracellular calcium variations using the formula of Tsien et al. (Tsien RY, Pozzan T, Rink TJ. Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J. Cell. Biol. 1982; 94(2): 325-334.) after adding a calcium ionophore (A23187 or ionomycin) and then EGTA (Ethylene Glycol Tetraacetic Acid). These intracellular calcium variations demonstrate the coupling of the receptor with an intracellular calcium system serving as a secondary messenger and showing 1) the presence of a primary receptor for the tested effector and 2) that calcium is a secondary messenger to this receptor. 2.5. Measurements of calpain enzymatic activity. Calpains are non-lysosomal cysteine proteases with papain-like calcium-dependent activity. These enzymes are responsible for calcium-dependent neutral proteolysis in a reducing environment. They are a family of proteins often associated with cellular inhibitors that play a key role in several cellular functions, particularly in synaptic plasticity and apoptosis. These proteins appear to be associated with certain neurodegenerative pathologies such as Alzheimer's and Parkinson's disease (Vosler PS, Brennan CS, Chen J. Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration. Mol. Neurobiol. 2008 38(1):78-100) and probably also in autism. In fact, in these diseases, the activation of these calpains could be due to high calcium levels and leads to hydrolysis of certain proteins or even their total degradation. Calpain activity is determined using a commercial kit (Axxora, Calpain Activity Assay Kit, ref: BV-K240-100). The principle of the assay is the fluorometric detection of the hydrolysis of a fluorogenic substrate measured with a fluorimeter. 2.6. Electrotransfer. 10 pg of protein solution (from cell or tissue lysate) are electrophoresed in a polyacrylamide gel in the presence of SDS (Sodium Dodecyl Sulfate) and then electrotransferred (Westem-Blott) onto a nitrocellulose membrane in a transfer buffer (for example: 39 mM glycine, 48 mM Tris, and 20% methanol). After saturating the membrane with a protein-enriched solution (milk, serum, etc.), it is exposed to a solution of primary antibodies which are then revealed with a solution of labeled secondary antibodies. This technique makes it possible to visualize the proteins of interest, particularly membrane receptors or proteins involved in intracellular signaling. 2.7. Production and / or secretion of glutamate. Neurotransmitters (notably GABA (Gamma Amino Butyric Acid) and glutamate) are both messengers of communication between neurons and essential players in brain construction. They could be involved in certain cases of autism (Collins AL, Ma D, Whitehead PL, Martin ER, Wright HH, Abramson RK, Hussman JP, Haines JL, Cuccaro ML, Gilbert JR, Pericak-Vance MA. Investigation of autism and GABA receptor subunit genes in multiple ethnic groups Neurogenetics. 2006; 7(3):167-174.) The amounts of glutamate released into the culture medium or into the tissue survival medium are determined using a commercial kit (for example, the “Amplex Red glutamic acid / glutamate oxidase assay kit” from Molecular Probes). The principle is a fluorometric measurement involving the fluorochrome Amplex Red, glutamate oxidase, glutamate pyruvate transaminase, alanine and peroxidase.After incubation at 37°C, the fluorescence of the reaction medium is measured (emission wavelength: 590 nm and excitation wavelength: 555 nm). 2.8. Electrophysiology techniques. These techniques allow the measurement of the electrical behavior of tissues or nerve cells during their stimulation or during the addition of different molecules. These classic techniques, known to those skilled in the art, are widely used for research in Neurobiology (The Neuronal Microenvironment. Editor(s): Alan A. Boulton, Glen B. Baker, Wolfgang Walz, University of Saskatchewan, Saskatchewan Canada, Springer). 2.9. Cytology and histology. The organs under study (especially the brain) are taken from the animal after anesthesia and fixed with a fixative solution (e.g., 4% paraformaldehyde in PBS) and then embedded in paraffin. They are cut into thin slices of a few microns. These sections are then stained (e.g., with a mixture of hematoxylin and eosin) and studied morphologically with an image analysis system. Alternatively, these sections are prepared and observed by electron microscopy techniques, using standard cytology and histology techniques known to those skilled in the art (Neurons: Methods and Applications for the Cell Biologist. Published by Peter J. Hollenbeck and James R. Bamburg. Academie Press, 2003, Amsterdam). 2.10. 3D brain imaging. Non-invasive imaging techniques applied to small animals (microNMR, Positron Emission Tomography (PET), scanner, etc.) are currently the technologies of choice in the exploration of various human pathologies, particularly in the cerebral domain. Due to the non-invasive nature of the exploration and the increasing development of new radiolabeled molecules, these techniques are of particular interest for neurobiology studies involving the use of appropriate ligands. In particular, these various imaging techniques are used to determine the target brain areas of the compounds described in patent FR2899973 and to study the effect of potential pharmacological antagonists. II Behavioral Tests 1. Definitions 1.1. Mouse called control Mice injected intraperitoneally with a physiological buffer solution. This buffer (PBS) has the following composition: 135 mM NaCl, 10 mM NaHPO4 / Na2HPO4, pH 7.4. This solution serves both as an injection control and as a solution to dissolve the compounds of interest tested. 1.2. VH Mouse Mice injected intraperitoneally with a solution (100 microL) composed of a physiological buffer containing dissolved vanillylhydracrylic acid (VH) at a concentration of 10 mg / kg. 1.3. AV Mouse Mice injected intraperitoneally with a solution (100 microL) composed of a physiological buffer containing dissolved vanillic acid (VA) at a concentration of 10 mg / kg. 1.4. AV+VH Mouse Mice injected intraperitoneally with a solution (100 microL) composed of a physiological buffer containing dissolved vanillylhydracrylic acid (VH) and vanillic acid (AV), both at a concentration of 10 mg / kg. 2. Description of the tests Four tests were performed: the open field test, the emergence test, the novel object test, and a test revealing social interactions. These tests are usually used in animal models studying the effects of toxic or pharmacological substances on behavioral changes. These tests reveal the effects of a substance on general exploratory activities, on reactions to a novel context, and on social interactions. They also allow us to assess the effects anxiogenic effects of the substances evaluated. These tests are therefore quite well suited for a first approach to a possible “autistic” effect of compounds since autism is revealed in part by an inadequacy of reactions to the environment, whether physical or social. These tests aim to determine the possible behavioral repercussions of vanillylhydracrylic acid (VH) and vanillic acid (VA) using 4-5 week old male SWISS white RjOrl(cd-l) mice as a model. The products are diluted in phosphate-buffered saline and administered intraperitoneally (100pL) to mice at concentrations of 10 mg / kg for each product. The mice are observed 30 minutes after injection. To establish a possible cumulative effect, the mice are injected daily for three days and analyzed consecutively over this 3-day period. Four cohorts of mice are treated with either a placebo (phosphate-buffered saline), the VH compound, vanillic acid alone, or both compounds, VH and vanillic acid. Groups of 10 mice per trial (AV, VH, or VH+VA) are analyzed and compared to the groups of 10 mice treated with the placebo. In practice, on the first and second days, the open field test and the emergence test are performed. Then on the third day, the open field test, the novel object test and the social interaction test are performed. The apparatus for the open field, novel object, and social interaction tests consists of a square (plastic) box, 37 cm across and 17 cm high, containing 16 squares of equal size drawn on the bottom of the box. The box is illuminated by ambient light. 2.1. The open field test The mice are placed individually in the center of the box and their movements are monitored for 5 minutes for 3 consecutive days. The number of total squares (measure of exploratory activity) and central squares crossed (least anxiety-provoking area) are quantified. The number of times the mice stand up on both hind legs, the number of times they groom and scratch, the duration of the moments of fixation, as well as the number of droppings and urines (criteria also expressing a possible feeling of anxiety) are also noted. 2.2. The new object test This test is performed only on the 3rd day immediately after the open field test by leaving the mouse in the box. This allows the mouse to be conditioned to the open box paradigm (open field) before placing the new object inside. The object is a metal cylinder 6.5 cm in diameter and 7 cm in height, placed at a distance from the mouse and outside its visual field. Care must be taken to place the object on a square adjacent to a bordering square of the box. Thus the object is placed on a central square but close to the edge of the box. The latency before the first contact with the object as well as the number of contacts with it are quantified during a period of 5 minutes under ambient light. 2.3. The social interaction test This test is performed immediately after the previous test and also only on the 3rd day. A second mouse of the same sex is placed in the center of the box at a distance and out of the visual field of the mouse being tested; the interactions are then followed for 5 min. A contact is considered positive if the nose of the mouse being tested is at a distance of less than 2 mm from the other mouse. All types of contacts are taken into consideration. 2.4. The emergence test This test is carried out on the first two days: a small dark box (8x8 cm), with only a small opening, is placed in the center of a larger box, different from the one used for the open field test (in order to avoid any recognition by the mouse of its environment). The mouse is placed in the small box and the time it takes to get out is noted. The times taken for the head, the two front legs, and then the four legs to move out are quantified over a maximum period of 5 minutes. 2.5. The seat preference test In this test, the mice are placed in two compartments, one light, the other dark, separated by a guillotine door. Each compartment (30x30 cm and 17 cm high) is divided into 9 squares drawn on the floor. The number of squares crossed per compartment is counted, as well as the number of passages between the two compartments and the time spent in each compartment over a total duration of 5 minutes. The whole is lit by ambient light. III Examples The behavioral studies described in the examples were conducted under standardized laboratory conditions. Thus, the main symptoms characterizing autistic subjects and which can be studied in animals were selected: spatial exploration abilities, neophobia, anxiety and finally, social interactions. 1. Examples of biological effects in point administration These measurements aim to determine the possible biological repercussions of the compounds involved in the present invention, and in particular of vanillylhydracrylic acid (VH) and vanillic acid (VA) by taking as a model male white SWISS mice RjOrl(cd-l) aged 4-5 weeks after a single administration in mice. The products are diluted in phosphate-buffered saline and administered intraperitoneally (100 μL) to mice at concentrations of 10 mg / kg for each product. The mice are studied 60 minutes after injection. Four cohorts of mice are treated with either a placebo (phosphate-buffered saline), the VH compound, vanillic acid alone, or both compounds, VH and vanillic acid. Groups of 10 mice per trial (AV, VH, or VH+VA) are analyzed and compared to the groups of 10 mice treated with the placebo. 60 minutes after injection, the mice are euthanized, and the rapidly removed brain is immediately ground in the presence of phosphate-buffered saline (PBS) containing protease inhibitors (Sigma). The ground material is then centrifuged (10,000 rpm, 10 minutes) and the supernatant is collected to measure: 1) protein concentration by the Bradford technique because all results are expressed per mg of protein, 2) calpain activity, 3) the concentration of glutamate, 4) the concentration of the compounds that were injected into the mice. 2. Examples of biological effects in chronic administration These measurements aim to determine the possible biological repercussions of the compounds involved in the present invention, and in particular of vanillylhydracrylic acid (VH) and vanillic acid (VA) using 4-5 week old male SWISS white RjOrl(cd-l) mice as a model after chronic administration in mice. The products are diluted in phosphate-buffered saline and administered intraperitoneally (100pL) to mice at concentrations of 10 mg / kg for each product. Four cohorts of mice are treated with either placebo (phosphate-buffered saline), VH compound, vanillic acid alone, or both compounds, VH and vanillic acid. Groups of 10 mice per trial (AV, VH, or VH+VA) are analyzed and compared to the groups of 10 mice treated with placebo. Mice are subjected to three successive injections on three consecutive days and then to three other successive injections on three consecutive weeks. The mice are studied 60 minutes after the last injection. The mice are then euthanized. and the rapidly removed brain is immediately ground in the presence of phosphate-buffered saline (PBS) containing protease inhibitors (Sigma). The ground material is then centrifuged (10,000 rpm, 10 minutes) and the supernatant is collected to measure: 1) protein concentration by the Bradford technique because all results are expressed per mg of protein, 2) calpain activity, 3) the concentration of glutamate, 4) the concentration of the compounds that were injected into the mice. 3. Examples of behavioral effects in point administration Example 1: Open Field Test In this example, the effect of three injections on three consecutive days of the VH, AV, or AV+VH compounds was determined. The various behavioral observations were made 30 min after the injection. The open field test shows a significant difference in the number of total squares crossed by AV+VH compared to the so-called control mice (Figure 1). However, no difference is found for the VH mice or the AV mice. In addition, it was observed that the so-called control mice explore their environment while the VH, AV or AV+VH mice seek to escape it. Thus, the exploratory abilities of the mice are modified by administration of a mixture of the two compounds AV and VH. Example 2: Emergence Test The emergence test allows the determination of a potential anxiogenic effect of a compound. 1) After a first administration, the so-called control mice leave the dark chamber after 6 + / - 5 sec, the torso after 11 + / - 7 sec and completely leave after 14 + / - 9 sec. After which they continue their exploratory behavior of their new environment. The AV mice leave the head after 2.2 + / - 1.2 sec, the torso after 5.4 + / - 4.4 sec and the complete body after 11.2 + / - 5.4 sec. The VH mice leave the head after 4.6 + / - 3.2 sec, the torso after 8.6 + / - 4.2 sec and the complete body after 18 + / - 15 sec. The AV+VH mice leave the head after 3.0 + / - 1.8 sec, the torso after 6.4 + / - 4.8 sec and the complete body after 9.2 + / - 3.2 sec. No significant difference was found between the so-called control mice and the treated mice. 2) After the second administration (the next day), the so-called control mice leave the dark enclosure after 1.8 + / - 0.2 sec, the torso after 3.0 + / - 0.4 sec and leave completely after 5 + / - 1.2 sec. This shorter time than the day before for these three parameters is explained by the fact that the mice already know this environment, which shows their rapid capacity for habituation, their capacity to memorize their environment and the reduction of fear generated by a known situation. The AV mice leave the head after 2.6 + / - 0.8 sec, the torso after 12.2 + / - 7.0 sec and the complete body after 14.0 + / - 5.2 sec. No notable behavioral variation is observed compared to the mice after a single administration. VH mice raised their heads after 7.4 + / - 4.2 sec, their torso after 10.4 + / - 4.8 sec; however, they never completely left their dark enclosure.AV+VH mice pop their heads out after 7.2 + / - 4.2 sec, their torso after 93 + / - 66 sec and also do not come out of the dark enclosure. This test shows a clear effect of both AV and VH compounds, this effect appearing additive. These effects are different: the AV compound prevents habituation while the VH compound is clearly anxiogenic. Example 3: Testing the new object This test is based on the spontaneous tendency of rodents to preferentially explore a new object. The so-called control mice react quickly to the introduction of the object into their environment since the first contact occurs after 5.4 + / - 2.4 seconds and for During the 5 min of the experiment they have 24 + / - 5.2 contacts with it. The time to first contact of AV mice with the new object is longer (14.8 + / - 7.6 sec) and the number of contacts a little lower (20.6 + / - 5.2). VH mice also have a longer time to first contact (15.0 + / - 8.2 sec) but an unchanged number of contacts (25.2 + / - 5.8). On the other hand, the time to first contact is longer in AV+VH mice (25 + / - 12 sec) and the number of contacts significantly reduced (7.8 + / - 3.4). In this test, increases in time to first contact with the novel object and a decrease in the number of contacts are indicative of an anxiogenic effect of the administered compounds. This effect is additive when AV and VH compounds are administered together. 4. Examples of behavioral effects in chronic administration In these examples, the compounds were administered to the mice for three consecutive days and then three more times for three consecutive weeks. Two weeks later, tests of place preference, emergence, novel object, and social interaction were performed. Example 1. Seat preference test Mice administered AV, VH, or the AV+VH mixture explored a new environment much less, unlike control mice. This decrease in exploration by injected mice no longer manifested itself when they were returned to their original cage, i.e., their usual environment. Under these conditions, their motor and / or exploratory behavior was identical to that of control mice. However, when they were taken out of their cage and placed on the floor, unlike control mice, which moved spontaneously, injected mice either exhibited escape behavior or remained motionless. This behavioral change was quantified by the place preference test. This test is based on the spontaneous tendency of rodents to explore their environment and avoid light (photophobia).The device consists of two compartments, one light, the other dark, separated by a guillotine door. Placed in this two-color enclosure of the place preference test, a device designed to quantify both the exploratory behavior of the animals and the anxiety that this exploration generates, the so-called control mice explore their new environment. In this test, the movements in each compartment, the number . of passage from one compartment to another as well as the respective times spent in each compartment are measured. The data are reported in Figures 2 to 4. The measurement of the total number of movements shows that the compounds reduce the exploratory activity of the mice and that the combination of the two products has an additive effect. The calculation of the number of movements made in the light compartment and the time spent in this compartment is an index of fear in relation to an environment considered to be more hostile (mice are nocturnal animals naturally fearing lit places). It is noted that the mice to which the compounds were administered fear an environment considered to be hostile more than the control mice Example 2. Emergence Test The emergence test is another test that reveals a possible anxiety-inducing effect of a product. The mice are introduced into a small dark enclosure placed in a larger light enclosure. The exit times of the head, the two front paws, and finally the entire body are noted. Under these experimental conditions, the mice are subjected to a choice: the safety of the dark enclosure and the curiosity to discover a new but uncertain environment. Figures 5 to 7 show that the so-called control mice do not stay very long in the dark enclosure; they completely exit after 10 seconds. The mice to which the compounds were administered emerge their heads and both front paws at times close to those of the so-called control mice. This means that they have similarly become aware of the presence of an external environment, but unlike the so-called control mice, they will not explore it or only very late.This result shows an anxiogenic effect of the administered compounds. Example 3. Testing the new object In this test, the latency time before the first contact and the number of contacts are noted. Figures 8 and 9 show the results obtained. Mice administered the compounds come into contact with the new object half as much as the so-called control mice. These results show either a significant decrease in the mice's natural curiosity or an anxiety-inducing effect of the products. Example 4. Social interaction test In this test, the mice are placed in the open field enclosure with another non-congener mouse from another cage, and given Calmivet (0.25 mg / kg, Vétoquinol Laboratory) was administered. It is a neuroplegic tranquilizer sometimes used as an anesthetic. Mice treated with Calmivet at this dose lose very little of their exploratory activity, but show a total lack of interest in a new congener. Thus, the contact time and the number of contacts measured in this test come solely from the initiative of the mice tested. The number of contacts decreases significantly in the mice to which the compounds were administered (Figure 10). The time to first contact is also increased in the VH mice (Figure 11). It is not significantly increased in the AV mice and in the AV+VH mice. The nature of the contacts is, however, very different in the mice to which the compounds were administered. In no case did the so-called control mice show signs of aggression towards the new mouse. This is not the case for the AV, VH and AV+VH mice.These all exhibited aggressive behavior, meaning they beat their tails (a sign of aggression in mice), and systematically attacked and bit the other mouse as it approached. Signs of prostration often accompanied this aggressive behavior; they placed themselves in a corner of the open field and did not move. The behavior of VH mice in the experimental situations described above resembles that of autistic subjects: neophobia and impoverished exploration, avoidance of social interactions. The results of this study show that mice administered the tested compounds can be used as an animal model of autism.
Claims
Claims 1) Use of at least one compound of the following formula I: in which: * n = 0 or 1, * Ra represents -CH2OH, -COOH, or -NR1R2, with RI and R2 representing, independently of each other, a hydrogen atom or an alkyl group of 1 to 3 carbon atoms, * Rb represents an alkyl group of 1 to 3 carbon atoms, * Z represents a hydrocarbon chain of 1 to 3 carbon atoms, optionally substituted by an OH group, said chain optionally comprising a -NH- and / or -CO- group, * said compounds being, where appropriate, in the form of salts or, when there is the presence of at least one asymmetric carbon, in the form of isomers alone or in a racemic mixture, for the preparation of a composition intended to create pervasive developmental disorders and / or psychiatric disorders in a non-human mammal, to which said composition has been administered. 2) Use according to claim 1, wherein the non-human mammal is selected from rat, hamster, gerbil, chinchilla, guinea pig, rabbit, monkey, ferret, pig, dog, or cat, and a mouse. 3) Use according to claim 1 or 2, wherein the pervasive developmental disorders and / or psychiatric disorders belong to the group comprising autism, developmental delays, or neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease. 4) Use according to one of claims 1 to 3, in which said compound corresponds to the following formula (I): (I) in which: * n = 0 or 1, * Ra represents -COOH, * Rb represents an alkyl group of 1 to 3 carbon atoms, * Z represents a hydrocarbon chain of 1 to 3 carbon atoms, optionally substituted by an OH group, said chain optionally comprising a -NH- and / or -CO- group, * said compounds being, where appropriate, in the form of salts or, when there is the presence of at least one asymmetric carbon, in the form of isomers alone or in a racemic mixture, said compound being responsible for the aforementioned disorders and / or problems. 5) Use according to one of claims 1 to 4, in which said compound corresponds to the following formula (II): (II) wherein n, Ra, and Z are as defined in claim 1 or 4, said compound being responsible for the above-mentioned disorders and / or disorders. 6) Use according to one of claims 1 to 5, in which said compound corresponds to formula (I) or (II), in which: * n = 0 or 1, * Ra represents -COOH, * Z represents -CH2-, -CHOH-, -CHOH-CH2-, -CH2-CHOH-, -CH2-CH2-,-CH2-CO-, or -CO-NH-CH2-, said compound being responsible for the aforementioned disorders and / or problems. 7) Use according to one of claims 1 to 5, of at least one compound corresponding to formula (I) or (II), in which: * n = 1, * Ra represents -COOH, * Rb represents -CH3, * Z represents -CH2-CHOH- to prepare a composition intended to create pervasive developmental disorders and / or psychiatric disorders in a non-human mammal. 8) Use according to claim 5, of at least one compound of formula (II) chosen from one of the following compounds: COOH ch2 Vanillylglycine Vanillic acid COOH COOH Vanillylpropionic acid 3-Methoxy-4-hy droxyphény 1- 3 -hy droxy-propionic acid to prepare a composition intended to create pervasive developmental disorders and / or psychiatric disorders in a non-human mammal. 9) Use according to claim 5, of a compound of the following formula: COOH I çh2 (3-methoxy-4-hydroxyphenyl-3-hydroxy-propionic acid, or vanillylhydracrylic acid) to prepare a composition intended to create pervasive developmental disorders and / or psychiatric disorders in a non-human mammal. 10) Use according to claim 5, of a compound of the following formula: COOH OH (vanillic acid) to prepare a composition intended to create pervasive developmental disorders and / or psychiatric disorders in a non-human mammal. 11) Use according to any one of claims 1 to 10, wherein the non-human mammal is a mouse. 12) Use of a non-human mammal with pervasive disorders developmental and / or psychiatric disorders, for the screening of therapeutic agents capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, in which has been administered at least one compound corresponding to the following formula (I): (I) in which: * n = 0 or 1, * Ra represents -CH2OH, -COOH, or -NR1R2, with RI and R2 representing, independently of each other, a hydrogen atom or an alkyl group of 1 to 3 carbon atoms, * Rb represents an alkyl group of 1 to 3 carbon atoms, * Z represents a hydrocarbon chain of 1 to 3 carbon atoms, optionally substituted by an OH group, said chain optionally comprising a -NH- and / or -CO- group, * said compounds being, where appropriate, in the form of salts or, when there is the presence of at least one asymmetric carbon, in the form of isomers alone or in a racemic mixture, said compound being responsible for the above-mentioned disorders and / or disorders, and a therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, and possibly including a comparison step between: the non-human mammal obtained following the administration of the above-mentioned compound and the above-mentioned therapeutic agent * the aforesaid non-human mammal to which the aforesaid compound has been administered, but the aforesaid therapeutic agent has not been administered, or * another healthy non-human mammal of the same species as that to which the above compound was administered, to which the above compound was administered, but the above therapeutic agent was not administered. 13) Use according to claim 12 of a non-human mammal, having pervasive developmental disorders and / or psychiatric disorders, for the screening of therapeutic agents capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, in which non-human mammal, was administered from 0.01 mg / kg to 100 mg / kg of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids in proportions ranging from 1 / 10 to 10 / 1, said compound being responsible for the above-mentioned troubles and / or disorders, and a therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, and possibly including a comparison step between: the non-human mammal, obtained following the administration of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids, and the above-mentioned therapeutic agent, and * the aforesaid non-human mammal, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids has been administered, but the aforesaid therapeutic agent has not been administered, or * another healthy non-human mammal of the same species as the one to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, but the above-mentioned therapeutic agent was not administered. 14) Use according to any one of claims 12 or 13, wherein the non-human mammal is a mouse. 15) Method for screening therapeutic agents capable of preventing, substantially reduce or reverse pervasive developmental disorders and / or psychiatric disorders from a non-human mammal administered: - at least one compound of the following formula (I): in which: * n = 0 or 1, * Ra represents -CH2OH, -COOH, or -NR1R2, with RI and R2 representing, independently of each other, a hydrogen atom or an alkyl group of 1 to 3 carbon atoms, * Rb represents an alkyl group of 1 to 3 carbon atoms, * Z represents a hydrocarbon chain of 1 to 3 carbon atoms, optionally substituted by an OH group, said chain optionally comprising a -NH- and / or -CO- group, * said compounds being, where appropriate, in the form of salts or, when there is the presence of at least one asymmetric carbon, in the form of isomers alone or in a racemic mixture, said compound being responsible for the above-mentioned disorders and / or disorders, and - at least one therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, including: at least one of the steps chosen from: * a step of blood and / or urine dosage, in vitro, of said compound or one of its metabolites from a sample originating from the above-mentioned non-human mammal in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a step of behavioral study of the above-mentioned non-human mammal in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a tissue and / or cellular study carried out on organs or tissues of the above-mentioned non-human mammal in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a whole animal study using imaging techniques, and possibly a comparison step between: the non-human mammal to which the above compound and the above therapeutic agent have been administered, and * the aforesaid non-human mammal to which the compound has been administered, but the therapeutic agent has not been administered, or * another healthy non-human mammal of the same species as that to which the above compound was administered, to which the above compound was administered, but the above therapeutic agent was not administered. 16) Screening method according to claim 15, of a therapeutic agent likely to prevent, reduce or substantially reverse pervasive developmental disorders and / or psychiatric disorders, from a non-human mammal, to which have been administered: from 0.01 mg / kg to 100 mg / kg of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids in proportions ranging from 1 / 10 to 10 / 1, said compound or mixture of compounds being responsible for the above-mentioned troubles and / or disorders, and at least one therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, including at least one of the steps chosen from: * a step of blood and / or urine dosage, in vitro, of said compound or one of its metabolites from a sample originating from the above-mentioned non-human mammal, in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a step of behavioral study of the above-mentioned non-human mammal, in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a tissue and / or cellular study carried out on organs or tissues of the above-mentioned non-human mammal, in which the above-mentioned compound and the above-mentioned therapeutic agent are administered, * a whole animal study using imaging techniques, and possibly a comparison step between: the non-human mammal, obtained following the administration of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids, and the above-mentioned therapeutic agent, and * the aforesaid non-human mammal, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids has been administered, but the aforesaid therapeutic agent has not been administered, or * another healthy non-human mammal of the same species as the one to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, but the above-mentioned therapeutic agent was not administered. 17) Screening method according to claim 15, of a therapeutic agent likely to prevent, reduce or substantially reverse pervasive developmental disorders and / or psychiatric disorders, from a non-human mammal, to which have been administered: from 0.01 mg / kg to 100 mg / kg of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids in proportions ranging from 1 / 10 to 10 / 1, said compound or mixture of compounds being responsible for the above-mentioned troubles and / or disorders, and at least one therapeutic agent capable of preventing, reducing or substantially reversing pervasive developmental disorders and / or psychiatric disorders, including: a step of behavioral study of the above-mentioned non-human mammal, in which the above-mentioned compound and the above-mentioned therapeutic agent have been administered, and possibly a comparison step between: the non-human mammal, obtained following the administration of vanillic acid or vanillylhydracrylic acid or a mixture of these two acids, and the above-mentioned therapeutic agent, and * the aforesaid non-human mammal, to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids has been administered, but the aforesaid therapeutic agent has not been administered, or * another healthy non-human mammal of the same species as the one to which vanillic acid or vanillylhydracrylic acid or a mixture of these two acids was administered, to which vanillic acid or vanillylhydracrylic acid vanillylhydracrylic acid or a mixture of these two acids was administered, but the above-mentioned therapeutic agent was not administered, 18) A screening method according to any one of claims 15 to 17, wherein the non-human mammal is a mouse.