Cannabinoids inhibit GABAergic synaptic transmission in mice nucleus accumbens

In mice nucleus accumbens slices, whole-cell patch clamp recording of mediu m-spiny neurons revealed that cannabimimetics ((R)-(+)-[2,3-dihydro-5-methy l-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphtalen ylmethanone) (WIN-2) and ((-)-cis-3-[2-hydroxy-4-( 1,1 -dimethylheptyl)-phe nyl]-trans-4-(3-hydroxypropyl)cyclohexanol) inhibit stimulus-evoked gamma-a minobutyric acid mediated inhibitory post-synaptic currents (IPSC). The act ions of WIN-2 were reversed by the selective cannabinoid CB1 receptor antag onist [N-piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl -1 H-pyrazole-3-carboximide hydrochloride] (SR141716A). WIN-2 modified pair ed-pulse ratio of evoked IPSCs and decreased miniature IPSC frequency indic ating a presynaptic localization of cannabinoid CB1 receptors. (C) 2001 Els evier Science B.V. All rights reserved.