Involvement of γ-aminobutyric acid neurotransmission in phencyclidine-induced dopamine release in the medial prefrontal cortex

Yuji Yonezawa, Toshihide Kuroki, Takeshi Kawahara, Nobutada Tashiro, Hideyuki Uchimura

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The present study was designed to examine the possible involvement of γ-aminobutyric acid (GABA) neurotransmission in the mechanism of phencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP)-induced dopamine release in the medial prefrontal cortex, using in vivo microdialysis in awake, freely moving rats. Local perfusion via the dialysis probe into the medial prefrontal cortex with PCP (100 and 500 μM) and dizocilpine ((+)-5-methyl-10,11-dihydroxy-5-H-dibenzo(a,d)cyclo-heptan-5,10-imine; MK-801, 10 and 50 μM), a selective non-competitive NMDA receptor antagonist, was found to increase extracellular dopamine levels. Co-perfusion with NMDA (1 mM) or the GABA(A) receptor agonist muscimol (50 μM) attenuated the effects of PCP (500 μM) and MK-801 (50 μM) on extracellular dopamine levels. The dopamine reuptake inhibitor nomifensine (50 μM) also produced an increase in extracellular dopamine levels in the medial prefrontal cortex, but this effect was not affected by co-perfusion with muscimol (50 μM). On the other hand, local perfusion with PCP (100 and 500 μM) and MK-801 (10 and 50 μM), but not nomifensine (50 μM), reduced extracellular GABA levels in the medial prefrontal cortex, Co-perfusion with NMDA (1 mM) reduced the effects of PCP (500 μM) and MK-801 (50 μM) on extracellular GABA levels. These results suggest that PCP may facilitate dopamine release in the medial prefrontal cortex, at least in part, by the inhibition of GABA release via the antagonism of NMDA receptors.

Original languageEnglish
Pages (from-to)45-56
Number of pages12
JournalEuropean Journal of Pharmacology
Volume341
Issue number1
DOIs
Publication statusPublished - Jan 2 1998

All Science Journal Classification (ASJC) codes

  • Pharmacology

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