Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common μ1 opioid receptor mechanism

The effects of the active ingredient of Cannabis, Δ- 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 oploid receptor mechanism located in the ventral mesencephalic tegmentum.