Phencyclidine (PCP) is a psychotomimetic agent of major importance for drug abuse research since it is one of the most widely abused street drugs. It may also produce a model psychosis. Current investigators suggest it may have a potent effect on brain dopaminergic (DA) systems but direct or indirect effects on GABA, serotonin (5-HT), acetylcholine (ACh) and norepinephrine (NE) neuronal systems appear to occur as well. To ascertain its principal modes of action, we plan to continue investigating the effects of PCP on turning behavior in unilaterally substantia-nigra lesioned rats, stereotypy and locomotor activity. Through direct administration of PCP to brain nuclei and lesioning, the nuclei involved in these behaviors will be ascertained. The effect of pharmacologic treatments which alter DA, 5-HT, GABA, NE or ACh synthesis, release, uptake or action at receptor sites on PCP-induced behaviors will be studied. We also plan to compare the effects of PCP with those of amphetamine on rat brain DA and 5-HT metabolism through regional studies of turnover of DA and 5-HT after both treatments or in conjunction with other treatments which affect DA turnover such as haloperidol and gammahydroxybutyrolactone (GHBL).