Involvement of potassium channels in the antidepressant-like effect of venlafaxine in mice

Abstract

Aims Studies have shown that the acute administration of venlafaxine elicits an antidepressant-like effect in the mouse forced swim test (FST) by a mechanism dependent on the l-arginine–nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway. Because it has been reported that NO activates different types of potassium (K +) channels in the brain, this study investigated the involvement of K + channels in the antidepressant-like effect of venlafaxine in the mouse FST. Main methods Male adult Swiss mice were pretreated with different K + channel inhibitors or openers 15 min before venlafaxine administration. After 30 min, the open-field test (OFT) and FST were carried out. Key findings Intracerebroventricular (i.c.v.) pretreatment of mice with subeffective doses of tetraethylammonium (TEA, a non-specific inhibitor of K + channels, 25 pg/site), glibenclamide (an ATP-sensitive K + channel 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) was able to potentiate the action of a subeffective dose of venlafaxine (2 mg/kg, i.p.). Moreover, the reduction in the immobility time elicited by an effective dose of venlafaxine (8 mg/kg, i.p.) in the FST was prevented by the pretreatment of mice with the K + channel openers cromakalim (10 µg/site, i.c.v.) and minoxidil (10 µg/site, i.c.v.). The drugs used in this study did not produce any change in locomotor activity. Significance The results demonstrate that the neuromodulatory effects of venlafaxine, via the inhibition of K + channels, are possibly involved in its anti-immobility activity in the mouse FST.