Phencyclidine (PCP) is a major drug of abuse in the United States. Little is currently known of the effects of PCP on neuroendocrine function. Preliminary studies have shown that the acute administration of PCP increases the release of corticosterone and inhibits the release of prolactin and luteinizing hormone in the rat. The proposed series of experiments will characterize the effects of the acute and chronic administration of PCP on the release of these three anterior pituitary hormones in the rat. Drug-induced changes in behavior will also be measured in order to compare and contrast the effects of PCP on these two phenomenon. The involvement of opiate receptors in PCP-induced changes in neuroendocrine function will be evaluated by testing for antagonism by narcotic antagonists and cross-tolerance with morphine. The hypothesis that PCP and drugs with sigma opiate receptor activity share a common receptor will be tested by comparing the endocrine effects of PCP with those produced by enantiomers of N-allylnormetazocine as well as cross-tolerance to N-allylnormetazocine in chronically PCP-treated animals. PCP will also be injected directly into the cerebral ventricles in order to determine the role of central versus peripheral mechanisms in drug-induced neuroendocrine changes. These studies may provide a new in vivo model test system with which to characterize potential pathophysiological changes which occur with PCP use and lead to inferences regarding the underlying mechanisms of action of this drug on the central nervous system.
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