Phencyclidine (PCP), also known as angel dust, is an important drug of abuse in the United States. In addition to producing profound changes in behavior, PCP disrupts neuroendocrine function and affects body temperature. While there are considerable data on the neurochemical basis of PCP-induced changes in behavior, there is little information on the neurochemical mechanisms underlying the effects of PCP on endocrine function and body temperature. The proposed studies will use selective agonists and antagonists to determine the role of sigma receptors in the effects of PCP on the release of ACTH and prolactin and in PCP-induced changes in body temperature in the rat. The hypothesis that dopaminergic and/or serotonergic mechanisms mediate some of the effects of PCP on neuroendocrine function and body temperature also will be tested by using selective antagonists, neurotransmitter synthesis inhibitors and neurotoxic lesions. Cocaine is known to affect dopaminergic and serotonergic neurotransmission, and possibly sigma receptors as well. The co-abuse of PCP and cocaine has become common on the street. Thus, from both a clinical and mechanistic standpoint, poly- and concurrent drug abuse is an important issue; however, there is little information on the physiological effects of this combination. The proposed studies also will characterize the effects of the co-administration of PCP and cocaine on neuroendocrine function and body temperature. Knowledge of the underlying fundamental mechanisms of action by which the effects of PCP are manifested is imperative in order to develop strategies with which the effects of PCP are manifested is imperative in order to develop strategies with which to prevent and possibly treat the sequelae of this major drug of abuse.
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