The Cannabinoid Receptor Agonist WIN 55,212-2 Reduces D2, but Not D1, Dopamine Receptor-Mediated Alleviation of Akinesia in the Reserpine-Treated Rat Model of Parkinson's Disease

• Published in: Experimental neurology Vol. 148; no. 1; pp. 265 - 270
• Main Authors: Maneuf, Y.P., Crossman, A.R., Brotchie, J.M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.11.1997; Elsevier
• Subjects: Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Basal Ganglia - drug effects; Basal Ganglia - physiopathology; Benzazepines - pharmacology; Benzazepines - therapeutic use; Benzoxazines; Biological and medical sciences; Dopamine Agonists - pharmacology; Dopamine Agonists - therapeutic use; gamma-Aminobutyric Acid - physiology; Locomotion - drug effects; Male; Medical sciences; Morpholines - pharmacology; Morpholines - toxicity; Naphthalenes - pharmacology; Naphthalenes - toxicity; Nerve Tissue Proteins - drug effects; Nerve Tissue Proteins - physiology; Neuropharmacology; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - drug therapy; Pharmacology. Drug treatments; Piperidines - pharmacology; Piperidines - therapeutic use; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Quinpirole - pharmacology; Quinpirole - therapeutic use; Rats; Rats, Sprague-Dawley; Receptors, Cannabinoid; Receptors, Dopamine D1 - drug effects; Receptors, Dopamine D1 - physiology; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - physiology; Receptors, Drug - agonists; Reserpine - toxicity; Rimonabant; Nervous system diseases; Agonist; Akinesia; Rat; Motor system disorder; Rodentia; D1 Dopamine receptor; Parkinson disease; Cannabinoid; Antiparkinson agent; Cerebral disorder; Vertebrata; Chemotherapy; Mammalia; D2 Dopamine receptor; Treatment; Animal; Central nervous system disease; Degenerative disease; Neurological disorder; Extrapyramidal syndrome; Biological receptor
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.1997.6645

The effects of the synthetic cannabinoid receptor agonist WIN 55,212-2 on dopamine receptor-mediated alleviation of akinesia were evaluated in the reserpine-treated rat model of parkinsonism. The dopamine D2receptor agonist quinpirole (0.1 mg/kg, ip) caused a significant alleviation of the akinesia. This effect was significantly reduced by coinjection with the cannabinoid receptor agonist WIN 55,212-2 (0.1 and 0.3 mg/kg). The simultaneous administration of the cannabinoid receptor antagonist SR 141716A (3 mg/kg, ip) with quinpirole and WIN 55,212-2 blocked the effect of WIN 55,212-2 on quinpirole-induced alleviation of akinesia. The selective dopamine D1receptor agonist chloro-APB (SKF82958, 0.1 mg/kg) alleviated akinesia in a significant manner. WIN 55,212-2 (0.1-1 mg/kg, ip) did not affect the antiakinetic effect of chloro-APB. Combined injection of both D1and D2dopamine receptor agonists (both at either 0.1 or 0.02 mg/kg) resulted in a marked synergism of the antiakinetic effect. WIN 55,212-2 (0.1–1 mg/kg) significantly reduced the antiakinetic effect of combined injections of quinpirole and chloro-APB at both 0.1 and 0.02 mg/kg. The effect of 0.3 mg/kg WIN 55,212-2 on combined D1and D2agonist-induced locomotion (0.02 mg/kg) was blocked by SR 141761A (3 mg/kg). Neither WIN 55,212-2 alone (0.1 and 0.3 mg/kg) nor SR 141716A (3 and 30 mg/kg) alone had an antiparkinsonian effect. These results suggest that cannabinoids may modulate neurotransmission in the pathway linking the striatum indirectly to basal ganglia outputs via the lateral globus pallidus and the subthalamic nucleus.