For a number of years this laboratory has been interested in the effects of abused substances on neurochemical and behavioral systems. The attempt has been to be able to correlate drug dosage (tissue concentration of the drug) with behavioral and biochemical manifestation in an attempt to delineate mechanisms. Research with the popular drug phencyclidine (angel dust) has demonstrated an interaction with catecholamine and cholinergic systems. Since these systems, particularly dopaminergic, have been demonstrated to play a strong role in hormonal regulation, we have chosen to hypothesize that PCP may 1) influence catecholamine systems in vivo as they have been found to do in vitro and 2) influence hormonal regulation. Sensitive neurochemical assays of endogenous amine release and radioimmune assays of prolactin will be employed to test these hypotheses. Since it is possible that PCP metabolites and/or the influences of PCP on catecholaminergic systems may mediate some of the drug's effects on cholinergic systems, we plan to utilize brain lesion and neurochemical analyses to examine this possibility. The findings of this research should provide 1) further insight into the sequelae of drug administration, 2) further information about the mechanisms of drug action, and possibly 3) information of importance to clinicians dealing with PCP abusers.