The effect of phencyclidine on dopamine synthesis and metabolism in rat striatum

J. D. Doherty, M. Simonovic, R. So, H. Y. Meltzer

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Previous behavioral and neurochemical studies indicate that phenyclidine (PCP), a potent psychotomimetic agent, interacts with central dopaminergic systems. We have examined the effects of PCP on the rate of accumulation of 3,4-dihydroxyphenylalanine (DOPA) after the inhibition of L-aromatic amino acid decarboxylase and on the levels of dopamine (DA) metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat striatum. PCP, in doses from 2.5 to 50 mg/kg, decreased the rate of striatal DOPA accumulation. PCP did not antagonize the increase in the rate of striatal DOPA formation caused by haloperidol, reserpine or γ-butyrolactone (GBL). When given alone, PCP decreased striatal levels of DOPAC and HVA, while it greatly potentiated the haloperidol-induced rise in striatal levels of these two metabolites. PCP is considerably less effective than d-amphetamine in promoting the release of 3H-DA from preloaded striatal slices in vitro. Our results are consistent with the interpretation that PCP potentiates the synaptic effects of endogenous DA. Its mechanism of action appears to be closely related to that of a category of drugs known as non-amphetamine stimulants, which, among others, includes methylphenidate, amfonelic acid and cocaine.

Original languageEnglish (US)
Pages (from-to)139-149
Number of pages11
JournalEuropean Journal of Pharmacology
Volume65
Issue number2-3
DOIs
StatePublished - 1980

Keywords

  • Dopamine agonist
  • Phencyclidine
  • Reuptake blocker

ASJC Scopus subject areas

  • Pharmacology

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