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Life Sci. 2010 Feb 27;86(9-10):372-6. doi: 10.1016/j.lfs.2010.01.013. Epub 2010 Jan 25.

Involvement of potassium channels in the antidepressant-like effect of venlafaxine in mice.

Author information

1
Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogens, Natural Science Institute, Federal University of Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.

Abstract

AIMS:

Studies have shown that the acute administration of venlafaxine elicits an antidepressant-like effect in the mouse forced swim test (FST) by a mechanism dependent on the l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Because it has been reported that NO activates different types of potassium (K(+)) channels in the brain, this study investigated the involvement of K(+) channels in the antidepressant-like effect of venlafaxine in the mouse FST.

MAIN METHODS:

Male adult Swiss mice were pretreated with different K(+) channel inhibitors or openers 15 min before venlafaxine administration. After 30 min, the open-field test (OFT) and FST were carried out.

KEY FINDINGS:

Intracerebroventricular (i.c.v.) pretreatment of mice with subeffective doses of tetraethylammonium (TEA, a non-specific inhibitor of K(+) channels, 25 pg/site), glibenclamide (an ATP-sensitive K(+) channel inhibitor, 0.5 pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K(+) channel inhibitor, 25 pg/site) or apamin (a small-conductance calcium-activated K(+) channel inhibitor, 10 pg/site) was able to potentiate the action of a subeffective dose of venlafaxine (2mg/kg, i.p.). Moreover, the reduction in the immobility time elicited by an effective dose of venlafaxine (8 mg/kg, i.p.) in the FST was prevented by the pretreatment of mice with the K(+) channel openers cromakalim (10 microg/site, i.c.v.) and minoxidil (10 microg/site, i.c.v.). The drugs used in this study did not produce any change in locomotor activity.

SIGNIFICANCE:

The results demonstrate that the neuromodulatory effects of venlafaxine, via the inhibition of K(+) channels, are possibly involved in its anti-immobility activity in the mouse FST.

PMID:
20102723
DOI:
10.1016/j.lfs.2010.01.013
[Indexed for MEDLINE]

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