Mu. Kappa and sigma opioid agonists have been shown to exert differential effects on complex behavioral processes. The present proposal is directed towards a continuation of research in the form of support for studies designed to characterize the effects of various opioids, both alone and in combination with other drugs of abuse, on the acquisition, retention and performance of complex discriminations. The first series of proposed studies involves a continuing characterization of the effects of various opioid agonists and antagonists on the acquisition and performance of discriminations in monkeys and rats. Such data may have significant implications concerning differences in the neuronal events mediating the various behavioral actions of opioids both within and across species. While endogenous opioids are thought to modulate memory, little is known concerning the effects of opioid on memory in primates. The second series of proposed studies is designed to provide a significant amount of new information concerning the effects of various opioid agonists and antagonists on memory in monkeys. It is well-documented that other drugs of abuse (e.g., cocaine) are frequently used in combination with the opioids. In light of these data the third series of proposed studies is designed to continue our characterization of the acute effects of opioids in terms of their interactions with various drugs of abuse. The fourth series of studies will characterize the combined effects of these same drugs when the opioid is administered on a chronic basis. Such studies may have dramatic and significant implications concerning not only the behavioral consequences of polydrug abuse, but also the clinical use of some of these drugs. For example, the development of new medications to treat drug abuse and their potential use in reducing several risk factors associated with AIDS infection in intravenous drug users are clinical areas which may be affected by such drug-interaction studies. The fifth series of studies will characterize the effects of various NMDA agonists and antagonists on the acquisition, retention and performance of discriminations in monkeys. These studies are significant in that they may elucidate specific mechanisms through which certain drugs of abuse alter learning and memory. Furthermore, investigations of the behavioral properties of various drugs affecting NMDA neurotransmission will provide new information which may be of potential value in the treatment of both phencyclidine-like drug dependence and overdose.
Showing the most recent 10 out of 24 publications
