Agmatine produces antidepressant-like effects in two models of depression in mice

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Abstract
Agmatine produces an antidepressant-like effect when assessed in the forced swimming test (FST) and in the tail suspension test (TST) in mice (dose range 0.01–50 mg/kg, i.p.), without accompanying changes in ambulation in an open-field. I.c.v. injection of agmatine (1–100 nmol/site) also reduced the immobility time in the FST. Agmatine significantly enhanced the anti-immobility effect of imipramine, but did not affect that of MK-801. The anti-immobility effect of agmatine assessed in the FST was not affected by pre-treatment with prazosin. In contrast, agmatine's antidepressant-like effect was completely prevented by pre-treatment of animals with yohimbine, GMP or L-arginine. Taken together these data demonstrate that agmatine elicited a significant antidepressant-like effect through a mechanism that seems to involve an interaction with NMDA receptors, the L-arginine-nitric oxide pathway and α2-adrenoceptors.