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 [3H]GABA uptake into slices of rat globus pallidus. delta 9-Tetrahydrocannabinol caused a concentration-dependent decrease in GABA uptake (51% decrease at 100 microM delta 9-tetrahydrocannabinol, IC50 = 18.95 microM). This effect was reversed in a concentration-dependent manner (IC50 = 11.9 microM) by the cannabinoid receptor antagonist SR 141716A (N-(piperidin-1-yl-)5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1 H-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.
Maneuf
Y P
YP
Division of Neuroscience, School of Biological Sciences, University of Manchester, UK.
Nash
J E
JE
Crossman
A R
AR
Brotchie
J M
JM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects* / Q000502:physiology; D000077285:Rimonabant; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D005680:gamma-Aminobutyric Acid; D013759:Dronabinol; D000077285:Rimonabant