Stimulation of synaptosomal tyrosine hydroxylation by phencyclidine in vitro

Phencyclidine (PCP), a potent psychoactive drug, produces some animal behaviors that are believed to be mediated by dopaminergic and/or cholinergic neurons in the basal ganglia. In this study, we have monitored the effects of PCP in vitro on the synthesis, uptake, and release of dopamine (DA) in rat striatal synaptosomes. Using tyrosine hydroxylation as an index of DA synthesis, we observed a concentration-dependent stimulation of DA synthesis by PCP. The stimulatory effect was antagonized by reserpine (1 micro M) and was observed only when synaptosomes were preincubated under conditions which prevented the spontaneous release of [3H]DA. Two hydroxylated metabolites of PCP were also tested and found to have little effect on tyrosine hydroxylation. Like PCP these metabolites are potent inhibitors of synaptosomal [3H]DA uptake, but they apparently lack PCP's ability to release synaptosomal DA. Taken together, these results support our hypothesis that PCP stimulates synaptosomal DA synthesis by releasing DA from an inhibitory pool.