Cannabinoid and Heroin Activation of Mesolimbic Dopamine Transmission by a Common µ ₁ Opioid Receptor Mechanism

TLDR

The study compared Δ9‑THC and heroin effects on nucleus accumbens dopamine in rats via microdialysis and showed that systemic naloxone or ventral tegmental μ1 antagonist naloxonazine blocked these effects. Δ9‑THC and heroin raise dopamine in the nucleus accumbens shell, an effect blocked by cannabinoid antagonist SR141716A for THC but not heroin, and by μ1 opioid antagonists, indicating both drugs act via a shared μ1 opioid receptor mechanism in the ventral tegmentum.

Abstract

The effects of the active ingredient of Cannabis , Δ 9 -tetrahydrocannabinol (Δ 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. Δ 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 Δ 9 -THC but not those of heroin. Naloxone, a generic opioid antagonist, administered systemically, or naloxonazine, an antagonist of μ 1 opioid receptors, infused into the ventral tegmentum, prevented the action of cannabinoids and heroin on dopamine transmission. Thus, Δ 9 -THC and heroin exert similar effects on mesolimbic dopamine transmission through a common μ 1 opioid receptor mechanism located in the ventral mesencephalic tegmentum.