Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors.
The present study was designed to determine if cannabinoids share with other drugs of abuse the ability to stimulate mesolimbic dopaminergic neurons and if this effect is mediated by cannabinoid receptors. To this end, the effects of the prototypical cannabinoid, delta9 tetrahydrocannabinol ¿(-)-trans-(6aR,10aR)-6a,7,8,10a-tetrahydro-6,6,9-trimethyl- 3-pentyl-6H-dibenzo[b,d]pyran-1-ol¿, and the two highly potent synthetic cannabinoids, ¿(R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)-methyl]pyrrolo[1,2,3-d e]-1,4-benzoxazin-6-yl, +(1-naphtalenyl)methanone¿ WIN 55,212-2 and ¿(-)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl )-cicloexan-1-ol¿ CP 55,940, on the spontaneous discharge rate of meso-accumbens dopamine (A10 dopamine) neurons were studied in rats. The intravenous administration of delta9-tetrahydrocannabinol, WIN 55,212-2 and CP 55,940 (0.0625-1.0 mg/kg) produced a dose-dependent increase in the spontaneous firing of A10 dopamine neurons both in non-anesthetized and anesthetized rats, with a maximal percent increase of 120, 187 and 155 in non-anesthetized and 33, 102 and 52, respectively, in anesthetized rats. The stimulant response to cannabinoids was suppressed by the specific cannabinoid receptor antagonist ¿N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide¿ SR 141716A, indicating a cannabinoid receptor-mediated effect. These findings support the contention that cannabinoids regulate mesolimbic dopamine transmission and may help to explain the addictive properties of marijuana.
Gessa
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B.B. Brodie Department of Neuroscience, University of Cagliari, Italy.
Melis
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Muntoni
A L
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Diana
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008032:Limbic System / Q000166:cytology; D008297:Male; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects*
D000777:Anesthetics; D002186:Cannabinoids; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D004298:Dopamine