Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors

摘要: Abstract The present study was designed to determine if cannabinoids share with other drugs of abuse the ability stimulate mesolimbic dopaminergic neurons and this effect is mediated by cannabinoid receptors. To end, effects prototypical cannabinoid, Δ 9 tetrahydrocannabinol {(−)-trans-(6a R ,10a )-6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol}, two highly potent synthetic cannabinoids, {( )-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)-methyl]pyrrolo[1,2,3- de ]-1,4-benzoxazin-6-yl,+(1-naphtalenyl)methanone} WIN 55,212-2 {(−)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)-cicloexan-1-ol} CP 55,940, on spontaneous discharge rate meso-accumbens dopamine (A 10 dopamine) were studied in rats. intravenous administration -tetrahydrocannabinol, 55,940 (0.0625–1.0 mg/kg) produced a dose-dependent increase firing A both non-anesthetized anesthetized rats, maximal percent 120, 187 155 33, 102 52, respectively, stimulant response suppressed specific receptor antagonist { N -(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide} SR 141716A, indicating receptor-mediated effect. These findings support contention that regulate transmission may help explain addictive properties marijuana.