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


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.


RESULTS
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.


CONCLUSIONS
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.
Bortolatto
Cristiani F
CF
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.
Jesse
Cristiano R
CR
Wilhelm
Ethel A
EA
Nogueira
Cristina W
CW
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000069470:Venlafaxine Hydrochloride