LAUSR

Although ethanol withdrawal depression is one of the prominent reasons for its reinstatement and dependence, its neurochemical basis is not clearly understood. Present study investigated the role of agmatinergic system in ethanol withdrawal-induced depression using forced swim test (FST) in rats. Chronic exposure of animals to ethanol for 21 days and its abrupt withdrawal produced depression like behavior as evidenced by increased immobility time in FST, compared to the pair-fed control animals. The ethanol withdrawal-induced depression was significantly attenuated by agmatine (20-40 μg/rat, i.c.v.), moxonidine (50 μg/rat, i.c.v.), 2-BFI (20 μg/rat, i.c.v.), L-arginine (80 μg/rat, i.c.v.), amino-guanidine (25 μg/rat, i.c.v.) and arcaine (50 μg/rat, i.c.v.) by their once daily administration during the withdrawal phase (Day 21, 22 and 23). The antidepressant effect of agmatine in ethanol withdrawn rats was potentiated by imidazoline receptor I1 agonist, moxonidine (25 μg/rat, i.c.v.) and imidazoline receptor I2 agonist 2-BFI (10 μg/rat, i.c.v.) at their sub-effective doses. On the other hand, it was completely blocked by imidazoline receptor I1 antagonist, efaroxan (10 μg/rat, i.c.v.) and imidazoline receptor I2 antagonist, idazoxan (4 μg/rat, i.c.v.). In addition, agmatine levels were significantly reduced in brain samples of ethanol withdrawn rats as compared to the pair-fed control animals. In conclusion, the present study suggests the importance of endogenous agmatinergic system and imidazoline receptors system in ethanol withdrawal-induced depression. The data projects agmatine as a potential therapeutic target for the alcohol withdrawal-induced depression.