NORADRENERGIC AND NITRIC OXIDE MODULATORS INFLUENCE ANTIDEPRESSANT EFFECTS OF AGOMELATINE IN MICE

Agomelatine is a synthetic analog of melatonin that is receiving attention as an alternative for the treatment of depression. The current study aimed to evaluated the involvement of the noradrenergic and nitric oxide (NO) pathway in the antidepressant effect of agomelatine. Male Swiss mice (26±3 g) were used. Agomelatine (40 mg/kg), imipramine (10 mg/kg, a tricyclic antidepressant), bupropion (10 mg/kg, dopamine /norepinephrine-reuptake inhibitor), prazosin (1 mg/kg, an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, an α2-adrenoceptor antagonist), and propranolol (2 mg/kg, a β-adrenoceptor antagonist), L-arginine (100 mg/kg, NO precursor), L-NAME (10 mg/kg, NO synthetase inhibitor), methylene blue (5mg/kg, guanylate cyclase inhibitor) were injected 30 min before administration of agomelatine, α-methyl-p-tyrosine (100 mg/kg, an inhibitor of tyrosine hydroxylase) was administered 3 h before agomelatine. All treatments were intraperitoneally, 1 ml/100g. Locomotor activity test, and forced swim test (FST) were performed an hour after agomelatine injection. The locomotor activity only reduced after imipramine or propranolol administration compared with the control group. Agomelatine decreased the immobility time during FST, but following its administration with imipramine it increased significantly compared with agomelatine alone. Agomelatine-prazosin, or AMPT significantly reduced immobility time compared with agomelatine alone. Immobility time deceased significantly after agomelatine and L-arginine were administered compared with agomelatine alone. While agomelatine with yohimbine, propranolol, L-NAME, or methylene blue insignificantly changed the results. Agomelatine proved potential antidepressant effects, that was enhanced by adrenergic or nitric oxide pathway modulation. Further research is warranted to determine the precise molecular mechanisms and optimize clinical applications.