Chronic agomelatine and fluoxetine induce antidepressant-like effects in H/Rouen mice, a genetic mouse model of depression
Résumé
The novel antidepressant agomelatine behaves as an agonist at melatonergic MT(1) and MT(2) receptors and as an antagonist at serotonin 5-HT(2C) receptors. This study investigated the effects of agomelatine and fluoxetine in a genetic model of depression called H/Rouen mice Male and female H/Rouen (helpless line) and NH/Rouen (nonhelpless line) mice, received once daily for 3 weeks agomelatine (10 and 50 mg/kgi.p.), fluoxetine (10 mg/kgi.p.) or vehicle. Immobility duration in the tail suspension test (TST) was assessed on day 1 (D1), day 8 (D8), day 15 (D15) and day 22 (D22). Locomotor activity in a novel environment was assessed on day 18 (D18) and anhedonia (2-bottle sucrose preference test) was considered after the end of chronic treatment, from days 22 to 25. Agomelatine (50 mg/kg) significantly reduced immobility at D15 (p<0.01), and D22 (p<0.001) in treated H/Rouen mice whereas agomelatine at 10 mg/kg did not induce a statistically significant change. Fluoxetine reduced immobility at D8 (p<0.01), D15 (p<0.001) and D22 (p<0.001). Locomotor activity was unchanged in all treated groups as compared to vehicle groups. In the sucrose test, there was a significant decrease in sucrose preference in H/Rouen mice compared with NH/Rouen mice receiving vehicle. Both agomelatine doses (10 mg/kg (p=0.05) and 50 mg/kg (p<0.001) as well as fluoxetine (p<0.001) significantly increased the sucrose preference in H/Rouen mice as compared with H/Rouen mice that had received vehicle. These data indicate that the novel antidepressant agomelatine has antidepressant-like properties in H/Rouen mice, a genetic model of depression.