Stimulation of synaptosomal tyrosine hydroxylation by phencyclidine in vitro

Thomas W. Vickroy, Kenneth M. Johnson

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Phencyclidine (PCP), a potent psychoactive drug, produces some animal behavior that are belived 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 μM) 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.

Original languageEnglish (US)
Pages (from-to)463-473
Number of pages11
JournalEuropean Journal of Pharmacology
Volume71
Issue number4
DOIs
StatePublished - May 22 1981

Keywords

  • Phencyclidine
  • Tyrosine hydroxylation

ASJC Scopus subject areas

  • Pharmacology

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