Abstract
The effects of the active ingredient of Cannabis, Delta9-tetrahydrocannabinol (Delta9-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. Delta9-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 Delta9-THC but not those of heroin. Naloxone, a generic opioid antagonist, administered systemically, or naloxonazine, an antagonist of micro1 opioid receptors, infused into the ventral tegmentum, prevented the action of cannabinoids and heroin on dopamine transmission. Thus, Delta9-THC and heroin exert similar effects on mesolimbic dopamine transmission through a common mu1 opioid receptor mechanism located in the ventral mesencephalic tegmentum.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzoxazines
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Dopamine / metabolism*
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Dronabinol / antagonists & inhibitors
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Dronabinol / pharmacology*
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Heroin / pharmacology*
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Male
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Microdialysis
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Morpholines / antagonists & inhibitors
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Morpholines / pharmacology
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Naloxone / analogs & derivatives
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Naloxone / pharmacology
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Naphthalenes / antagonists & inhibitors
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Naphthalenes / pharmacology
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Narcotic Antagonists / pharmacology
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Nucleus Accumbens / drug effects*
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Nucleus Accumbens / metabolism
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Piperidines / pharmacology
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Pyrazoles / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Cannabinoid
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Receptors, Drug / antagonists & inhibitors
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Receptors, Drug / metabolism
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Receptors, Opioid, mu / antagonists & inhibitors
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Receptors, Opioid, mu / metabolism*
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Rimonabant
Substances
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Benzoxazines
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Morpholines
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Naphthalenes
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Narcotic Antagonists
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Piperidines
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Pyrazoles
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Receptors, Cannabinoid
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Receptors, Drug
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Receptors, Opioid, mu
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Naloxone
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(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
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Heroin
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Dronabinol
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naloxonazine
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Rimonabant
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Dopamine