The cannabinoid agonists WIN 55,212-2 and CP 55,940 attenuate rotational behavior induced by a dopamine D1 but not a D2 agonist in rats with unilateral lesions of the nigrostriatal pathway.

The effect of cannabinoid receptor stimulation on rotational behavior induced by a dopamine D1 and a D2 agonist was studied in rats with unilateral 6-hydroxydopamine-induced lesions of the dopaminergic nigrostriatal pathway. The cannabinoid agonists WIN 55,212-2 (2.5 mg/kg) and CP 55,940 (0.1 mg/kg) both markedly attenuated contralateral rotation induced by the D1 agonist SKF 38393 (1.5 mg/kg). In contrast, WIN 55,212-2 and CP 55,940 did not alter rotation elicited by the D2 agonist quinpirole (0.1 mg/kg). Doses of WIN 55,212-2 and CP 55,940 that attenuated D1-mediated rotation did not produce catalepsy in intact rats or in rats with 6-hydroxydopamine-induced lesions, indicating that the reduction in rotation produced by the cannabinoids was not due to a generalized motor impairment. In addition, the effective dose of WIN 55,212-2, but not CP 55,940, produced only a slight increase in ipsilateral rotation when administered alone, making it improbable that this ipsilateral tendency accounts for the reduction in D1-mediated contralateral rotation. These results suggest a preferential interaction between cannabinoid receptor stimulation and dopamine D1 receptor-mediated behavior.