The present invention is directed to the production of PKC isozyme
.epsilon. (PKC.epsilon.)-deficient cells and non-human animals. The
present invention is further directed to the identification of
PKC.epsilon. as a target for drugs that reduce anxiety. According to the
present invention, PKC.epsilon.-inhibiting compounds act in synergy with
drugs acting at the GABA.sub.A receptor. The present invention is also
directed to the use of modulators of PKC.epsilon. 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 PKC.epsilon.,
either alone or in conjunction with allosteric agonists of GABA.sub.A
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 GABA.sub.A 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 .epsilon. (PKC.epsilon.); the use of PKC.epsilon. as a target for
drugs; the use of inhibitors of PKC.epsilon. in methods of reducing
anxiety and treating conditions associated with insufficient activity of
the GABA.sub.A receptor; the use of modulators of PKC.epsilon. 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 PKC.epsilon. and allosteric
agonists of GABA.sub.A receptors; and the identification of individuals
with enhanced susceptibility to alcoholism or other forms of addiction.