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Science 27 June 1997:
Vol. 276. no. 5321, pp. 2048 - 2050
DOI: 10.1126/science.276.5321.2048
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Reports

Cannabinoid and Heroin Activation of Mesolimbic Dopamine Transmission by a Common µ1 Opioid Receptor Mechanism

Gianluigi Tanda, Francesco E. Pontieri, * Gaetano Di Chiara dagger

The effects of the active ingredient of Cannabis, Delta 9-tetrahydrocannabinol (Delta 9-THC), and of the highly addictive drug heroin on in vivo dopamine transmission in the nucleus accumbens were compared in Sprague-Dawley rats by brain microdialysis. Delta 9-THC and heroin increased extracellular dopamine concentrations selectively in the shell of the nucleus accumbens; these effects were mimicked by the synthetic cannabinoid agonist WIN55212-2. SR141716A, an antagonist of central cannabinoid receptors, prevented the effects of Delta 9-THC but not those of heroin. Naloxone, a generic opioid antagonist, administered systemically, or naloxonazine, an antagonist of µ1 opioid receptors, infused into the ventral tegmentum, prevented the action of cannabinoids and heroin on dopamine transmission. Thus, Delta 9-THC and heroin exert similar effects on mesolimbic dopamine transmission through a common µ1 opioid receptor mechanism located in the ventral mesencephalic tegmentum.

Department of Toxicology and Consiglio Nazionale delle Ricerche (CNR), Center for Neuropharmacology, University of Cagliari, Viale A. Diaz 182, 09126 Cagliari, Italy.
*   Present address: Department of Neuroscience, University "La Sapienza," Viale dell'Università 30, 00185 Roma, Italy.

dagger    To whom correspondence should be addressed.

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