This proposal is to continue our studies of the behavioral effects of phencyclidine (PCP) in laboratory animals. PCP abuse remains a serious public health problem, and since this drug is a relatively recent entry into the drug arena, relatively little is known about it. Previous studies have found that PCP shares many effects with drugs from other chemical classes including psychotomimetic opioids such as cyclazocine and 1,3-substituted dioxolanes. We propose to continue our studies of similarities by investigating the discriminative stimulus properties (a model for subjective drug effects) of other opioids and novel dioxolanes currently being synthesized. We also propose to extend our studies of the overlap in the pharmacology of these and some other PCP-like drugs to studies of their i.v. self-administration by rhesus monkeys, their ability to produce stereotyped behavior, their anticonvulsant effects, their interactions with phenobarbital, and their effects on punished responding. These studies will have implications for the extent of similarity of PCP to other drugs and for the cellular mechanism of action of PCP and related drugs. We will also be undertaking a search for an antagonist for PCP. Finally, we propose to investigate central sites of actions for PCP by direct intracerebral injections. A more complete understanding of the behavioral pharmacology of PCP is essential to developing effective treatments for PCP abuse.
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