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PMID: 9651235 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 18 ·No. 14 ·1998-07-15 ·Pages 5545-54

Adams B, Moghaddam B

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 hyperstimulation, may be necessary to account for the psychotomimetic and cognitive-impairing effects of this drug.

MeSH Terms
Animals Cognition/drug effects Dopamine/metabolism,physiology Glutamic Acid/metabolism Hallucinogens/pharmacology Male Motor Activity/drug effects Nucleus Accumbens/drug effects Phencyclidine/pharmacology Prefrontal Cortex/drug effects Rats Rats, Sprague-Dawley Stereotyped Behavior/drug effects Synaptic Transmission/drug effects Time Factors
Chemicals
Hallucinogens Glutamic Acid Phencyclidine Dopamine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Adams B
Department of Psychiatry, Yale University School of Medicine, Veterans Administration Medical Center, West Haven, Connecticut 06516, USA.
Moghaddam B
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1998-07-15
Pages
5545-54
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6793475
Subset
IM
Grants
NIMH NIH HHS · R01 MH048404 · United States
NIMH NIH HHS · R37 MH048404 · United States
NIMH NIH HHS · MH44866 · United States
NIMH NIH HHS · MH48404 · United States
External Links
PubMed source PMC Full Text View journal details
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