title: Involvement of different types of potassium channels in the antidepressant-like effect of ascorbic acid in the mouse tail suspension test.
abstract: 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 μg/site, i.c.v.) and minoxidil (10 μg/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.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, 88040-900 SC, Brazil.
authors.forename: Morgana
authors.initials: M
authors.lastname: Moretti
authors.forename: Josiane
authors.initials: J
authors.lastname: Budni
authors.forename: Camille Mertins
authors.initials: CM
authors.lastname: Ribeiro
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001030:Apamin / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D018999:Charybdotoxin / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D001030:Apamin; D019789:Tetraethylammonium; D001205:Ascorbic Acid; D005905:Glyburide