Modulation of morphine and alcohol motor stimulant effects by cannabinoid receptors ligands.
Previous studies evidenced in rats the suppression by cannabinoids of motor stimulant effects of various drugs of abuse. Here we investigated, in mice, the effects of an acute or a chronic administration with the cannabinoid agonist HU 210 on the motor stimulant effects of either morphine or alcohol. HU 210 (12.5-200 microg/kg), when acutely administered, antagonized the stimulant effects of morphine (7.5 mg/kg) or alcohol (1 or 1.5 g/kg). A tolerance to this antagonistic interaction with morphine and alcohol occurred after a 7-day or a 14-day HU 210 treatment, leading to the reappearance of morphine- and alcohol-induced stimulation. The CB1 receptor antagonist rimonabant (10 mg/kg) enhanced the stimulant effect induced by low doses of morphine (5 or 7.5 mg/kg). Rimonabant (3 or 10 mg/kg) altered the locomotor effect of alcohol in a biphasic manner. It enhanced the stimulant effect of low doses of alcohol (1 or 1.5 g/kg) while decreasing the locomotor activity of mice treated with a high dose (3 g/kg) of alcohol. Furthermore, rimonabant (3 and 10 mg/kg) enhanced the duration of alcohol-induced loss of righting reflex (4 g/kg), suggesting a dual implication of cannabinoidergic pathways in acute effects of alcohol.
Hagues
Guillaume
G
Unité de Neuropsychopharmacologie Expérimentale, CNRS FRE 2735, IFRMP 23, Faculté de Médecine et de Pharmacie de Rouen, 22, Bd Gambetta, 76183 Rouen Cedex, France.
Costentin
Jean
J
Duterte-Boucher
Dominique
D
D000704:Analysis of Variance; D000818:Animals; D063387:Cannabinoid Receptor Antagonists; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D004336:Drug Antagonism; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008024:Ligands; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D000077285:Rimonabant; D018709:Statistics, Nonparametric
D063387:Cannabinoid Receptor Antagonists; D000697:Central Nervous System Stimulants; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D000431:Ethanol; D009020:Morphine; D013759:Dronabinol; C062018:HU 211; D000077285:Rimonabant