This study examined the effects of acute administration of delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive ingredient in marijuana, on extracellular efflux of dopamine (DA) and its metabolites as measured by in vivo microdialysis in nucleus accumbens of conscious, freely-moving rats. Δ9-THC, at low doses (0.5-1.0 mg/kg), which significantly enhance brain stimulation reward (intracranial self-stimulation), significantly increased DA efflux in nucleus accumbens. Augmentation of DA efflux by Δ9-THC was abolished by removal of calcium (Ca++) ions from the perfusion fluid, indicating a Ca++-dependence of Δ9-THC's action. Augmentation of DA efflux by Δ9-THC was either totally blocked or significantly attenuated by doses of naloxone as low as 0.1 mg/kg. Given the postulated role of mesocorticolimbic DA circuits in mediating and/or modulating brain stimulation reward, the present data raise the possibility that marijuana's rewarding effects, and hence its euphorigenic effects and abuse potential, may be related to pharmacological augmentation of presynaptic DA mechanisms. Additionally, the DA mechanisms enhanced by marijuana appear to be modulated by an endogenous opioid peptide system.
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