We will continue our research into the effect of phencyclidine (PCP) on identified ctecholaminergic neuronal pathways in rat central nervous system. Using electrophysiological and electrochemical techniques, we have characterized PCP as an indirect dopamineergic agonist in caudate and as an indirect noradrenergic agonist in cerebellum and hippocampus. In the present application, we will extend this work to consideration of dopaminergic pathways arising in the ventral tegmental area, which project to nucleus accumbens and frontal cortex. We will study these structures in intact anesthetized animals, as well as isolated neuronal circuits transplanted in oculo and in situ. We will extend our pharmacological studies to include interaction between sigma opiates and PCP. We will also study the effects of repeated administration of PCP over several weeks on electrochemical and electrophysiological parameters of catecholaminergic neurotransmission. Finally, we will chracterize the effects of PCP in unanesthetized freely-moving animals and then, in this preparation, study catecholaminergic neurotransmission during PCP self-administration.
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