Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade 88040-900, Florianópolis, SC, Brazil.
Pharmacol Biochem Behav. 2012 Mar;101(1):148-54. doi: 10.1016/j.pbb.2011.12.008. Epub 2011 Dec 29.
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.
钾 (K(+)) 通道与抑郁症的发生机制以及抗抑郁药的作用机制有关。鉴于几项研究表明叶酸在抑郁症的病理生理学中发挥着重要作用，本研究探讨了钾通道在这种维生素的抗抑郁样作用中的参与情况。为此，研究了不同类型的 K(+) 通道阻滞剂和叶酸联合给药对强迫游泳试验 (FST) 的影响。通过脑室内 (i.c.v.) 途径给予亚有效剂量的格列本脲（一种 ATP 敏感性 K(+) 通道阻滞剂，0.5pg/部位）、芋螺毒素（一种大电导和中电导钙激活 K(+) 通道阻滞剂，25pg/部位）或 apamin（一种小电导钙激活 K(+) 通道阻滞剂，10pg/部位），可增强叶酸（10mg/kg，po，亚有效剂量）在 FST 中的作用。此外，叶酸和 K(+) 通道阻滞剂单独或联合给药不会影响旷场试验中的运动。此外，用更高剂量（50mg/kg，po）给予叶酸可减少 FST 中的不动时间，而这种作用可被 K(+) 通道 opener cromakalim（10μg/部位，i.c.v.）预处理所阻止，而不影响运动活动。本研究结果表明，叶酸在 FST 中的抗抑郁样作用至少部分归因于其对神经元兴奋性的调节作用，通过抑制 K(+) 通道。
