Anxiolytic-like activity of agomelatine and melatonin in three animal models of anxiety.
The activity of the novel antidepressant agomelatine was evaluated in three models of anxiety and compared with that of melatonin and two anxiolytics, diazepam and buspirone. All drugs were tested 2 h before and 2 h after the dark phase of the diurnal cycle. Morning and evening agomelatine (10-75 mg/kg) administration increased animals' responses in the elevated plus maze and Vogel tests. Melatonin (10-75 mg/kg) enhanced open arms exploration in the evening experiment and was inactive in the Vogel test. In the conditioned ultrasonic vocalization test, agomelatine, but not melatonin, was active in the morning and evening experiment. Melatonin antagonist, S22153 (20 mg/kg), enhanced the action of morning and evening agomelatine administration in the Vogel and conditioned ultrasonic vocalization tests, while in the elevated plus maze test, S22153 inhibited effects of evening but not morning melatonin and agomelatine administration. These results indicate the involvement of both the melatonin and the 5-HT2C receptors in the mechanism of anxiolytic-like action of agomelatine.
Papp
Mariusz
M
Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland. nfpapp@cyf-kr.edu.pl
Litwa
Ewa
E
Gruca
Piotr
P
Mocaër
Elisabeth
E
D000081:Acetamides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology; D019454:Chronotherapy; D003214:Conditioning, Classical / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004597:Electroshock; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects; D044094:Receptors, Melatonin / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology; D014828:Vocalization, Animal / Q000187:drug effects; D009281:Naphthalenes
D000081:Acetamides; D014151:Anti-Anxiety Agents; D002065:Buspirone; D003975:Diazepam; D008550:Melatonin; D044405:Receptor, Serotonin, 5-HT2C; D044094:Receptors, Melatonin; D013876:Thiophenes; C120267:S 22153; C084711:agomelatine; D009281:Naphthalenes