Activation of the cannabinoid receptor by Delta(9)-tetrahydrocannabinol reduces gamma-aminobutyric acid uptake in the globus pallidus

The interaction between GABA (gamma-aminobutyric acid) and cannabinoids in the globus pallidus was investigated by evaluating the effects of Delta(9)-tetrahydrocannabinol on [H-3]GABA uptake into slices of rat globus pallidus. Delta(9)-Tetrahydrocannabinol caused a concentration-dependent decrease in GABA uptake (51% decrease at 100 mu M Delta(9)-tetrahydrocannabinol, IC50=18.95 mu M). This effect was reversed in a concentration-dependent manner (IC50=11.9 mu M) by the cannabinoid receptor antagonist SR 141716A (N-(piperidin-1-yl-)5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-arboxiamidehydrochloride. SR 141716A alone did not affect GABA uptake. These results show that cannabinoid receptor activation reduces GABA uptake in the globus pallidus.