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Δ9-Tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis

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Abstract

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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Authors and Affiliations

  1. Division of Substance Abuse, Albert Einstein College of Medicine, 10461, New York, NY, USA

    Joyce Lowinson

  2. Department of Psychiatry, Albert Einstein College of Medicine, 10461, New York, NY, USA

    William Paredes, Jin Li, Diane Smith, Joyce Lowinson & Eliot L. Gardner

  3. Department of Neuroscience, Albert Einstein College of Medicine, 10461, New York, NY, USA

    Jianping Chen & Eliot L. Gardner

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  1. Jianping Chen
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  2. William Paredes
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  3. Jin Li
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  4. Diane Smith
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  5. Joyce Lowinson
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Chen, J., Paredes, W., Li, J. et al. Δ9-Tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis. Psychopharmacology 102, 156–162 (1990). https://doi.org/10.1007/BF02245916

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  • DOI: https://doi.org/10.1007/BF02245916

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