CANNABINOID AND HEROIN ACTIVATION OF MESOLIMBIC DOPAMINE TRANSMISSIONBY A COMMON MU-1 OPIOID RECEPTOR MECHANISM

The effects of the active ingredient of Cannabis, Delta(9)-tetrahydroc annabinol (Delta(9)-THC), and of the highly addictive drug heroin on i n vivo dopamine transmission in the nucleus accumbens were compared in Sprague-Dawley rats by brain microdialysis, Delta(9)-THC and heroin i ncreased extracellular dopamine concentrations selectively in the shel l of the nucleus accumbens; these effects were mimicked by the synthet ic 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 s ystemically, or naloxonazine, an antagonist of mu(1) opioid receptors, infused into the ventral tegmentum, prevented the action of cannabino ids and heroin on dopa mine transmission. Thus, Delta(9)-THC and heroi n exert similar effects on mesolimbic dopamine transmission through a common mu(1) opioid receptor mechanism located in the ventral mesencep halic tegmentum.