The CB1 cannabinoid receptor antagonist SR 141716A affects A9 dopamine neuronal activity in the rat.

CB1 receptors and their putative natural ligand anandamide, have been tentatively involved in the control of midbrain extrapyramidal function. Electrophysiological activity of dopamine neurones was measured after acute and repeated administration of the CB1 receptor antagonist SR 141716A (0.3-3 mg kg-1) in rats. Acute SR 141716A increased A9, but not A10 cell population response without affecting either their spontaneous firing rate or apomorphine-induced rate inhibition and prevented amphetamine-induced inhibition of A9, but not of A10 cell firing. After repeated administration SR 141716A (1 or 5 mg kg-1) decreased population response of A9 cells, which was reversed by apomorphine. These results suggest that CB1 receptor blockade by SR 141716A interrupts a cannabinoid-like endogenous tone controlling extrapyramidal function.