title: Antidepressant-like effects of the cannabinoid receptor ligands in the forced swimming test in mice: mechanism of action and possible interactions with cholinergic system.
abstract: The purpose of the experiments was to explore the role of the endocannabinoid system, through cannabinoid (CB) receptor ligands, nicotine and scopolamine, in the depression-related responses using the forced swimming test (FST) in mice. Our results revealed that acute injection of oleamide (10 and 20 mg/kg), a CB1 receptor agonist, caused antidepressant-like effect in the FST, while AM 251 (0.25-3 mg/kg), a CB1 receptor antagonist, did not provoke any effect in this test. Moreover, acute administration of both CB2 receptor agonist, JWH 133 (0.5 and 1 mg/kg) and CB2 receptor antagonist, AM 630 (0.5 mg/kg), exhibited antidepressant action. Antidepressant effects of oleamide and JWH 133 were attenuated by acute injection of both non-effective dose of AM 251, as well as AM 630. Among the all CB compounds used, only the combination of non-effective dose of oleamide (2.5 mg/kg) with non-effective dose of nicotine (0.5 mg/kg) caused an antidepressant effect. However, none of the CB receptor ligands, had influence on the antidepressant effects provoked by nicotine (0.2 mg/kg) injection. In turn, the combination of non-effective dose of oleamide (2.5 mg/kg); JWH (2 mg/kg) or AM 630 (2 mg/kg), but not of AM 251 (0.25 mg/kg), with non-effective dose of scopolamine (0.1 mg/kg), exhibited antidepressant properties. Indeed, all of the CB compounds used, intensified the antidepressant-like effects induced by an acute injection of scopolamine (0.3 mg/kg). Our results provide clear evidence that the endocannabinoid system participates in the depression-related behavior and through interactions with cholinergic system modulate these kind of responses.
authors: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4a Street, 20-093 Lublin, Poland. Electronic address: marta.kruk@umlub.pl.
authors: Marta
authors: M
authors: Kruk-Slomka
authors: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4a Street, 20-093 Lublin, Poland.
authors: Agnieszka
authors: A
authors: Michalak
authors: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4a Street, 20-093 Lublin, Poland.
authors: Grazyna
authors: G
authors: Biala
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D007211:Indoles / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D009829:Oleic Acids / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D002186:Cannabinoids; D007211:Indoles; D008024:Ligands; D009829:Oleic Acids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C103505:AM 251; D009538:Nicotine; C029407:oleylamide; D012601:Scopolamine; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC; C094023:iodopravadoline
keywords: Cholinergic system; Depression; Endocannabinoid system; Forced swimming test; Mice