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.
Anderson
L A
LA
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Anderson
J J
JJ
Chase
T N
TN
Walters
J R
JR
D000818:Animals; D048588:Benzoxazines; D002186:Cannabinoids; D003342:Corpus Striatum / Q000502:physiology; D003511:Cyclohexanols / Q000494:pharmacology*; D007839:Functional Laterality / Q000502:physiology; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D011955:Receptors, Drug / Q000819:agonists*; D012399:Rotation; D013378:Substantia Nigra / Q000502:physiology
D048588:Benzoxazines; D002186:Cannabinoids; D003511:Cyclohexanols; D009025:Morpholines; D009281:Naphthalenes; D043882:Receptors, Cannabinoid; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D016627:Oxidopamine