The combination of agomelatine and ritanserin exerts a synergistic interaction in passive avoidance task.
Agomelatine is a potent agonist at melatonergic 1 and 2 (MT1 and MT2) receptors and an antagonist at serotonin-2C (5HT-2C) receptors. It was suggested that psychotropic effects of agomelatine is associated with its melatonergic and serotonergic effects. In this study, we aimed to evaluate the effects of agomelatine alone or in combination with ritanserin (5HT-2A/2C antagonist) on memory and learning. Male Balb-C mice (25-30 g) were used, and all drugs and saline were administrated by intraperitoneal (i.p.) route 30 min prior to evaluating retention time. Whilst agomelatine was administered at the doses of 1, 10 and 30 mg/kg, ritanserin was administered at the doses of 0.1, 1 and 10 mg/kg. To evaluate memory function, passive avoidance test was used. On the first day, acquisition time and on the second day (after 24h), retention time of mice were recorded. To evaluate the synergistic activity, only the least doses of agomelatine and ritanserine were used, that is, 1 and 0.1 mg/kg, respectively. Scopolamine (1 mg/kg) was used as a reference drug, so it was combined with drug groups. Our results show that 5HT-2A/2C receptor antagonist ritanserin (1 and 4 mg/kg, i.p.) and agomelatine (10 and 30 mg/kg, i.p.) improve memory deficit induced by scopolamine, whilst a synergistic interaction is observed between ritanserin and agomelatine (0.1 mg/kg and 1 mg/kg, i.p., respectively) when they were administered at their ineffective doses. According to our findings, we concluded that agomelatine improves memory deficit and thus improves the effect of agomelatine arises from its 5HT-2C receptor antagonist activity.
Department of Pharmacology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey fatihilkaya@gmail.com.
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İlkaya
Department of Medicine Child and Adolescent Psychiatry, Ondokuz Mayıs University, Samsun, Turkey.
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Yüce
Department of Pharmacology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey.
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Ağrı
Department of Pharmacology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey.
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Güzel
Department of Pharmacology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey.
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Balcı
Department of Medicine Child and Adolescent Psychiatry, Ondokuz Mayıs University, Samsun, Turkey.
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Uçar
Department of Medicine Child and Adolescent Psychiatry, Ondokuz Mayıs University, Samsun, Turkey.
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Babadağı
Department of Medicine Child and Adolescent Psychiatry, Ondokuz Mayıs University, Samsun, Turkey.
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Müjdeci
Department of Pharmacology, Faculty of Medicine, Ordu University, Ordu, Turkey.
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Mutlu
D000081:Acetamides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D004357:Drug Synergism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016713:Ritanserin / Q000008:administration & dosage / Q000494:pharmacology*; D009281:Naphthalenes
D000081:Acetamides; D016713:Ritanserin; C084711:agomelatine; D009281:Naphthalenes
Agomelatine; passive avoidance; ritanserin; serotonin 2 receptors; synergism