Cocaine abuse has risen sharply over the past 10 years, and with this increase has come a commensurate increase in the health and social problems associated with chronic cocaine use. Effective strategies for dealing with this problem depend on an appreciation of the factors that contribute to drug use. In the case of cocaine, it is generally believed that drug-induced changes in affect (both euphoria and dysphoria) are important determinants of the pattern of drug self-administration. However, few studies have attempted to evaluate the time course of cocaine's mood-altering effects. The research described in this proposal explores the time course of cocaine-induced changes in affect using an intracranial self- stimulation paradigm. Fluctuations in train durations thresholds will be used to investigate the effects of chronic cocaine administration of central reward mechanisms. In addition, the ability of drugs coadministered with cocaine (i.e., ethanol and morphine) will be evaluated for their ability to modify cocaine- induced changes in self-stimulation. Finally, the influence of imipramine on cocaine's effects will be assessed to determine whether this drug, which has been proposed as a treatment for cocaine dependence, alters cocaine-induced euphoria and/or dysphoria.
