| 摘要 |
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. |
