α-noradrenergic receptor modulation of the phencyclidine- and Δ9- tetrahydrocannabinol-induced increases in dopamine utilization in rat prefrontal cortex

J. David Jentsch, Alyssa Wise, Zachary Katz, Robert H. Roth

Research output: Contribution to journalArticle

Abstract

The noncompetitive NMDA receptor antagonist phencyclidine (PCP) and the neuronal cannabinoid receptor agonist Δ9-tetrahydrocannabinol (THC) are two agents shown to have psychotomimetic properties in humans. Both drugs increase dopamine release and utilization in the prefrontal cortex, a brain region thought to be dysfunctional in schizophrenia. In the present series of studies, the effects of drugs acting at α-noradrenergic receptors on PCP- and THC-induced increases in prefrontal cortical and nucleus accumbens dopamine utilization in the rat were examined. Clonidine, an α2 noradrenergic receptor agonist, completely blocked the activation of mesoprefrontal dopamine system by THC or PCP. In addition, the α1 noradrenergic receptor antagonist prazosin blocked the PCP-induced increase in prefrontal cortical dopamine utilization. These data may provide new insights concerning pharmacological therapies for acute drug-induced psychoses and behavioral abnormalities in human PCP and THC abusers.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalSynapse
Volume28
Issue number1
DOIs
StatePublished - Jan 1998

Keywords

  • Clonidine
  • Guanfacine
  • Nucleus accumbens
  • Prazosin
  • Psychotomimetic

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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