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

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Science  27 Jun 1997:
Vol. 276, Issue 5321, pp. 2048-2050
DOI: 10.1126/science.276.5321.2048

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The effects of the active ingredient of Cannabis, Δ9-tetrahydrocannabinol (Δ9-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. Δ9-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 Δ9-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, Δ9-THC and heroin exert similar effects on mesolimbic dopamine transmission through a common μ1 opioid receptor mechanism located in the ventral mesencephalic tegmentum.

  • * Present address: Department of Neuroscience, University “La Sapienza,” Viale dell'Università 30, 00185 Roma, Italy.

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