Agomelatine attenuates the expression of nicotine-induced locomotor sensitization in male rats

Nicotine, the primary psychoactive component of tobacco, is known to influence mood. Antidepressants are considered potential treatments for reducing the reinforcing effects of smoking and aiding cessation. Agomelatine, a melatonin-dependent antidepressant, functions as an agonist of MT 1 and MT 2 melatonin receptors and an antagonist of 5-HT 2B and 5-HT 2C serotonin receptors. Notably, it has previously been shown to decrease the reinforcing and neurochemical effects of cocaine in Wistar rats. Therefore, the present study aimed to investigate agomelatine’s effect on locomotor activity and the expression of nicotine-induced locomotor sensitization. Using the nicotine locomotor sensitization paradigm, we evaluated agomelatine’s effects on both nicotine-induced locomotor activity and the nicotine-induced locomotor sensitization. Agomelatine (10 mg/kg, i.p.) was administered during nicotine withdrawal and expression phase. Our findings indicate that agomelatine attenuated the expression of locomotor sensitization induced by multiple doses of nicotine. Additionally, agomelatine reduced both the duration of locomotor effects and the overall locomotor activity following binge nicotine administration in male rats. Thus, the results of this study suggest that agomelatine reduced nicotine-induced locomotor activity and nicotine-induced locomotor sensitization and support the need for further preclinical studies before proposing its use in clinical trials.