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.