Role of Potassium Channels in the Antidepressant-like Effect of Folic Acid in the Forced Swimming Test in Mice

Potassium (K(+)) channels have been implicated in depressive disorders and in the mechanism of action of antidepressants. Considering that several studies have indicated that folic acid plays an important role in the pathophysiology of depression, the present study investigated the involvement of potassium channels in the antidepressant-like effect of this vitamin. For this aim, the effect of the combined administration of different types of K(+) channel blockers and folic acid in the forced swimming test (FST) was investigated. Treatment of mice by intracerebroventricular (i.c.v.) route with subactive doses of glibenclamide (an ATP-sensitive K(+) channels blocker, 0.5pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K(+) channel blocker, 25pg/site) or apamin (a small-conductance calcium-activated K(+) channel blocker, 10pg/site), augmented the effect of folic acid (10mg/kg, p.o., subeffective dose) in the FST. Additionally, the administration of folic acid and the K(+) channel blockers, alone or in combination, did not affect locomotion in the open-field test. Moreover, the reduction in the immobility time in the FST elicited by folic acid administered at a higher dose (50mg/kg, p.o.) was prevented by the pretreatment of mice with the K(+) channel opener cromakalim (10μg/site, i.c.v.), without affecting locomotor activity. The results of this study indicate that the antidepressant-like effect of folic acid in the FST may be at least partly due to its modulatory effects on neuronal excitability, via inhibition of K(+) channels.