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Persistent and anatomically selective reduction in prefrontal cortical dopamine metabolism after repeated, intermittent cannabinoid administration to rats
Author(s) -
Verrico Christopher D.,
Jentsch J. David,
Roth Robert H.
Publication year - 2003
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10215
Subject(s) - nucleus accumbens , dopamine , prefrontal cortex , dopaminergic , cannabinoid , striatum , neuroscience , ventral striatum , mesolimbic pathway , psychology , endocrinology , medicine , chemistry , ventral tegmental area , receptor , cognition
Long‐term abuse of delta‐9‐tetrahydrocannabinol (THC), the major psychoactive constituent of marijuana, produces behavioral and metabolic signs of frontal cortical dysfunction in humans; these effects persist even after short‐term abstinence. Based on a preliminary finding that repeated administration of THC to rats reduces basal frontal cortical dopamine turnover (Jentsch et al. [1998] Neurosci Lett 246:169–172), we further investigated the effects of repeated administrations of THC or WIN 55,212‐2 (WIN), a synthetic cannabinoid receptor agonist, on dopamine turnover in the prefrontal cortex, striatum, and nucleus accumbens. THC or WIN (twice daily for 7 or 14 days) caused a persistent and selective reduction in medial prefrontal cortical dopamine turnover; no significant alterations of dopamine metabolism were observed in the nucleus accumbens or striatum. Importantly, these dopaminergic deficits in the prefrontal cortex were observed after a drug‐free period of up to 14 days. Thus, the cognitive dysfunction produced by heavy, long‐term cannabis use may be subserved, in part, by drug‐induced alterations in frontal cortical dopamine turnover. Synapse 49:61–66, 2003. © 2003 Wiley‐Liss, Inc.