Cannabinoids inhibit GABAergic synaptic transmission in mice nucleus accumbens.
In mice nucleus accumbens slices, whole-cell patch clamp recording of medium-spiny neurons revealed that cannabimimetics ((R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphtalenylmethanone) (WIN-2) and ((-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)-phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) inhibit stimulus-evoked gamma-aminobutyric acid mediated inhibitory post-synaptic currents (IPSC). The actions of WIN-2 were reversed by the selective cannabinoid CB(1) receptor antagonist [N-piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride] (SR141716A). WIN-2 modified paired-pulse ratio of evoked IPSCs and decreased miniature IPSC frequency indicating a presynaptic localization of cannabinoid CB(1) receptors.
Manzoni
O J
OJ
CNRS UPR 9023, 141 Rue de la Cardonille, 34094 Cedex 05, Montpellier, France. manzoni@ccipe.montp.inserm.fr
Bockaert
J
J
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000502:physiology
D000700:Analgesics; D002186:Cannabinoids; D003511:Cyclohexanols; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D005680:gamma-Aminobutyric Acid; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol