Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine

Barbara Adams, Bita Moghaddam

Research output: Contribution to journalArticle

306 Scopus citations

Abstract

The behavioral syndrome produced by phencyclidine (PCP) and its analog ketamine represents a pharmacological model for some aspects of schizophrenia. Despite the multifaceted properties of these drugs, the main mechanism for their psychotomimetic and cognitive-impairing effects has been thought heretofore to involve the corticolimbic dopamine system. The present study examined the temporal relationship between alterations in corticolimbic dopamine and glutamate neurotransmission and two dopamine- dependent behavioral effects of PCP in the rodent that have relevance to the clinical phenomenology, namely, impairment of working memory, which is used to model the frontal lobe deficits associated with schizophrenia, and hyperlocomotion, which is used as a predictor of the propensity of a drug to elicit or exacerbate psychosis. PCP increased dopamine and glutamate efflux in the prefrontal cortex and nucleus accumbens, as measured by microdialysis. The increase in dopamine in both regions remained elevated well above baseline 2.5 hr after the injection, at which time the experiment was terminated. However, locomotor activity returned to baseline in <2 hr after injection. Furthermore, impaired performance in a discrete trial delayed alternation task, a rodent working memory task, was only evident up to 60 min after PCP injection; animals tested 80 min after injection, when cortical dopamine release was elevated at 300% of baseline, did not exhibit impaired performance. These findings indicate that activation of dopamine neurotransmission is not sufficient to sustain PCP-induced locomotion and impairment of working memory. Thus, effects of PCP, including a glutamatergic hyper-stimulation, may be necessary to account for the psychotomimetic and cognitive-impairing effects of this drug.

Original languageEnglish (US)
Pages (from-to)5545-5554
Number of pages10
JournalJournal of Neuroscience
Volume18
Issue number14
DOIs
StatePublished - Jul 15 1998

Keywords

  • Drug abuse
  • Glutamate
  • Ketamine
  • Microdialysis
  • NMDA
  • Nucleus accumbens
  • PCP
  • Prefrontal cortex
  • Schizophrenia
  • Working memory

ASJC Scopus subject areas

  • Neuroscience(all)

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