Journal
SYNAPSE
Volume 49, Issue 1, Pages 61-66Publisher
WILEY
DOI: 10.1002/syn.10215
Keywords
Delta(9)-tetrahydrocannabinol; Win 55,212-2; nucleus accumbens; dorsal striatum
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Funding
- NIMH NIH HHS [MH14092] Funding Source: Medline
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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 246:169172), 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. (C) 2003 Wiley-Liss, Inc.
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