title: Modulation of morphine and alcohol motor stimulant effects by cannabinoid receptors ligands.
abstract: 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.
authors.affiliation: Unité de Neuropsychopharmacologie Expérimentale, CNRS FRE 2735, IFRMP 23, Faculté de Médecine et de Pharmacie de Rouen, 22, Bd Gambetta, 76183 Rouen Cedex, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Hagues
authors.forename: Jean
authors.initials: J
authors.lastname: Costentin
authors.forename: Dominique
authors.initials: D
authors.lastname: Duterte-Boucher
mesh_terms: 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
chemical_list: 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