Involvement of different types of potassium channels in the antidepressant-like effect of ascorbic acid in the mouse tail suspension test

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• 作者：Morgana Moretti ; Josiane Budni ; Camille Mertins Ribeiro ; Ana Lú ; cia S. Rodrigues ; ^{analucia@mbox1.ufsc.br} ; ^{alsrodri@gmail.com}
• 关键词：Antidepressant ; Ascorbic acid ; K+ channel ; Tail suspension test
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：15 July, 2012
• 卷：687
• 期：1-3
• 页码：21-27
• 文件大小：615 K

摘要

Considering that the administration of ascorbic acid elicits an antidepressant-effect in mice by a mechanism which involves an interaction with N-methyl-d-aspartate receptors and the l-arginine-nitric oxide-cGMP pathway and taking into account that the stimulation of this pathway is associated with the activation of potassium (K⁺) channels, this study investigated the involvement of different types of K⁺ channels on the effect of ascorbic acid in the mouse tail suspension test (TST). Intracerebroventricular administration of tetraethylammonium (TEA, a non-specific blocker of K⁺ channels, 25 pg/site), glibenclamide (an ATP-sensitive K⁺ channel blocker, 0.5 pg/site), charybdotoxin (a large- and intermediate conductance calcium-activated K⁺ channel blocker, 25 pg/site) or apamin (a small-conductance calcium-activated K⁺ channel blocker, 10 pg/site) was able to produce a synergistic effect with a sub-effective dose of ascorbic acid (0.1 mg/kg) given orally (p.o.). The antidepressant-like effect of ascorbic acid (1 mg/kg, p.o.) in the TST was prevented by the pre-treatment of mice with cromakalim (a K⁺ channel opener, 10 渭g/site, i.c.v.) and minoxidil (10 渭g/site, i.c.v.). Moreover, cromakalim abolished the synergistic effect elicited by the combined treatment with sub-effective doses of ascorbic acid and 7-nitroindazole. The administration of the K⁺ channel modulators alone or in combination with ascorbic acid did not affect the locomotion of mice. Together, our results show that the antidepressant-like effect of ascorbic acid in the TST may involve, at least in part, the modulation of neuronal excitability, via inhibition of K⁺ channels.