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

Eur J Pharmacol. 2012 Jul 15;687(1-3):21-7. doi: 10.1016/j.ejphar.2012.04.041. Epub 2012 May 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Apamin / pharmacology
  • Ascorbic Acid / pharmacology*
  • Behavior, Animal / drug effects
  • Charybdotoxin / pharmacology
  • Female
  • Glyburide / pharmacology
  • Hindlimb Suspension
  • Male
  • Mice
  • Motor Activity / drug effects
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels / physiology*
  • Tetraethylammonium / pharmacology


  • Antidepressive Agents
  • Potassium Channel Blockers
  • Potassium Channels
  • Charybdotoxin
  • Apamin
  • Tetraethylammonium
  • Ascorbic Acid
  • Glyburide