Aim of the present study was to determine whether agomelatine could affect ethanol withdrawal-induced depression-like behavior through M1/M2 receptor agonist, serotonin 5-HT2c antagonist and 5-HT1-A agonist in mice. This study investigated the role of a melatonergic M1/M2 receptor agonist, serotonin 5-HT2C antagonist and 5-HT1-A agonist. Novel anti depressant agomelatine, melatonin and their combine effect with 5-HT1-A agonist 8-OH DPAT on ethanol withdrawal induced depression using tail suspension (TST) test in mice. Male mice received an ethanol-containing (1.6%, 3.6%, 6.3%) liquid diet for 10 days and were tested for withdrawal signs and symptoms at 2, 4, 6, 8, 10 h after termination of the diet on day 11. Agomelatine, melatonin and diazepam significantly reduced these signs of hyper excitability (EWS). The depression effect of ethanol withdrawal was attenuated by treatment with melatonin (10mg/kg), agomelatine (50 mg/kg, i.p.), 8-OH DPAT (1 mg/kg, i.p.). Ethanol-withdrawn mice treated with, melatonin and 8-OH DPAT displayed decreased duration of immobility than ethanol control mice. Agomelatine was more potent than Melatonin in reversing ethanol withdrawal-induced increase in duration of immobility. Agomelatine combination with 8-OH DPAT was more potent than given alone. Locomotor activity was unchanged in all treated groups compared to control groups. In conclusion, agomelatine was shown to possess antidepressant effects in the mice TST and melatonergic agonist, 5-HT2C antagonist and 5-HT1-A agonist properties could be involved in these effects.
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