The present invention is directed to the production of PKC
isozyme epsi (PKCepsi)-deficient cells and non-human animals. The present invention is further directed to the identification of PKCepsi as a target for drugs that reduce
anxiety. According to the present invention, PKCepsi-inhibiting compounds act in
synergy with drugs acting at the
GABAA receptor. The present invention is also directed to the use of modulators of PKCepsi to modulate
alcohol consumption, self-administration of other
drugs of abuse, and the effects of
alcohol consumption as well as the use of inhibitors of PKCepsi, either alone or in conjunction with allosteric agonists of GABAA receptors, to treat conditions, such as
addiction,
withdrawal syndrome,
skeletal muscle spasms, convulsive seizures, and
epilepsy, that are amenable to treatment by allosteric agonists of GABAA receptors. Additional aspects of the present invention are
diagnostic methods for identifying individuals at risk for becoming alcoholics or abusers of other drugs and kits for performing such
diagnostic methods. The present invention relates to: cells and non-human animals deficient for the PKC
isozyme epsi (PKCepsi); the use of PKCepsi as a target for drugs; the use of inhibitors of PKCepsi in methods of
reducing anxiety and treating conditions associated with insufficient activity of the
GABAA receptor; the use of modulators of PKCepsi in methods of modulating
alcohol consumption, modulating self-administration of other
drugs of abuse, and altering the effects of alcohol; pharmaceutical compositions comprising inhibitors of PKCepsi and allosteric agonists of GABAA receptors; and the identification of individuals with enhanced susceptibility to alcoholism or other forms of
addiction.