TY - JOUR T1 - Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors JF - Journal of Psychiatry and Neuroscience JO - JPN SP - 126 LP - 133 VL - 29 IS - 2 AU - Michel Bourin AU - Elisabeth Mocaƫr AU - Roger Porsolt Y1 - 2004/03/01 UR - http://jpn.ca/content/29/2/126.abstract N2 - Objective: To study agomelatine (S 20098), a potent agonist at melatonin receptors and antagonist at serotonin-2C (5-HT2C) receptors, in an animal model of depression, namely, the rodent forced swimming test (FST).Methods: The effects of acute and repeated administration of S 20098 were compared with those of melatonin (4, 8, 16, 32, 64 mg/kg intraperitoneally [IP] for mice), imipramine (64 mg/kg orally for rats, 8 mg/kg IP for mice) and fluoxetine (16 mg/kg IP for mice). The influence of the pretreatments with 5-HT1A or 5-HT1B receptor agonists (8-OH-DPAT, anpirtoline) and 5-HT1A/1B, 5-HT2A/2C or 5-HT3 antagonists (pindolol, ritanserin, ondansetron) on the effects of S 20098 or melatonin were compared with imipramine and fluoxetine in mice.Results: Acute or repeated (13 days) administration of S 20098 or imipramine in rats significantly decreased the duration of immobility during the FST at all doses. A dose-dependent effect was observed after the repeated treatment with S 20098. When given for 10 days to mice in the evening, S 20098 was active on the FST at doses of 4, 16 and 32 mg/kg, whereas the acute administration of S 20098 (in the morning and evening) was without any significant effect. Acute or repeated administration of S 20098 did not modify the locomotor activity of mice. The combination of S 20098 with the above-mentioned pretreatments enhanced the effects of S 20098, given alone, on the duration of immobility. By comparison, acute melatonin was inactive in the FST and only pretreatment with 8-OH-DPAT or pindolol revealed an anti-immobility effect. A pretreatment with 8-OH-DPAT also induced antiimmobility effects with imipramine, but not fluoxetine, whereas pindolol exerted additive effects with fluoxetine but not imipramine.Conclusion: These results demonstrate the antidepressant-like activity of repeated administration of S 20098 in the FST. Moreover, the combination of 5-HT agonists and antagonists leads to more powerful effects with S 20098 than with melatonin, thereby emphasizing the contribution of 5-HT receptors to the antidepressant activity of S 20098. Compared with imipramine and fluoxetine, the 5-HT receptor subtypes that may be involved in the antidepressant-like activity of S 20098 are not similar. Indeed, when considering the binding properties of S 20098, the 5-HT2C receptor subtype appears to be the most attractive candidate. It is concluded that the antidepressant-like activity of S 20098 in this model most probably involves a combination of both its melatonin agonist and 5-HT2C receptor antagonist properties. ER -