title: Antidepressant-like effects of agomelatine (S 20098) in the learned helplessness model.
abstract: To confirm the antidepressant-like activity of agomelatine (S 20098), a melatonin agonist and 5-hydroxytryptamine2C antagonist, already reported in the chronic mild stress and forced swimming tests, the effects of agomelatine were investigated in the learned helplessness test and compared with those of imipramine, melatonin and a selective 5-hydroxytryptamine2C antagonist, SB-242 084. Agomelatine was administered for 5 days either once a day or twice a day, and the effects of pretreatment by a melatonin receptor antagonist, S 22153 (20 mg/kg/day), were studied. A deficit in avoidance learning was observed in helpless control animals. Agomelatine (10 mg/kg/day) administered once a day significantly reduced this deficit with an effect similar to that of imipramine. Effects of agomelatine were abolished by S 22153 pretreatment. Melatonin or SB-242 084 did not reduce the deficit of helpless control animals. These results confirm the antidepressant-like activity of agomelatine and suggest a role of melatonin receptors in its mechanism of action.
authors.affiliation: Biotrial, Department of Preclinical Pharmacology, Rennes, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bertaina-Anglade
authors.forename: Christophe Drieu
authors.initials: CD
authors.lastname: la Rochelle
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Boyer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mocaër
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D006380:Helplessness, Learned; D007099:Imipramine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044094:Receptors, Melatonin / Q000819:agonists* / Q000037:antagonists & inhibitors; D058830:Serotonin 5-HT2 Receptor Antagonists; D013876:Thiophenes / Q000494:pharmacology; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000631:Aminopyridines; D000928:Antidepressive Agents; D007099:Imipramine; D007211:Indoles; D008550:Melatonin; D044094:Receptors, Melatonin; D058830:Serotonin 5-HT2 Receptor Antagonists; D013876:Thiophenes; C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; C120267:S 22153; C084711:agomelatine; D009281:Naphthalenes