Role of different types of potassium channels in the antidepressant-like effect of agmatine in the mouse forced swimming test

The administration of agmatine elicits an antidepressant-like effect in the mouse forced swimming test by a mechanism dependent on the inhibition of the NMDA receptors and the L-arginine-nitric oxide (NO) pathway. Since it has been reported that the NO can activate different types of potassium (K+) channels in several tissues, the present study investigates the possibility of synergistic interactions between different types of K+ channel inhibitors and agmatine in the forced swimming test. Treatment of mice by i.c.v. route with subeffective doses of tetraethylammonium (a non specific inhibitor of K+ channels, 25 pg/site), glibenclamide (an ATP-sensitive K+ channels inhibitor, 0.5 pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K+ channel inhibitor, 25 pg/site) or apamin (a small-conductance calcium-activated K+ channel inhibitor, 10 pg/site), augmented the effect of agmatine (0.001 mg/kg, i.p.) in the forced swimming test. Furthermore, the administration of agmatine and the K+ channel inhibitors, alone or in combination, did not affect locomotion in the open-field test. Moreover, the reduction in the immobility time elicited by an active dose of agmatine (10 mg/kg, i.p.) in the forced swimming test was prevented by the pre-treatment of mice with the K channel openers cromakalim (10 mu g/site, i.c.v.) and minoxidil (10 mu g/site, i.c.v.), without affecting locomotion. Together these data raise the possibility that the antidepressant-like effect of agmatine in the forced swimming test is related to its modulatory effects on neuronal excitability, via inhibition of K+ channels. (C) 2007 Elsevier B.V. All rights reserved.