Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effect of baclofen in mouse forced swimming test

Background previous study confirmed that the acute treatment with baclofen by inhibition of the l-arginine-nitric oxide (no) pathway diminished the immobility behavior in the forced swimming test (fst) of mice. considering the involvement of no in adenosine triphosphate (atp)-sensitive potassium channels (katp),in the present study we investigated the involvement of katp channels in antidepressant-like effect of baclofen in the fst. methods after assessment of locomotor behavior in the open-field test (oft),fst was applied for evaluation of the antidepressant-like activity of baclofen in mice. baclofen at different doses (0.1,0.3,and 1 mg/kg) and fluoxetine (20 mg/kg) were administrated by intraperitoneal (ip) route,30 min before the fst or oft. to clarify the probable involvement of katp channels,after determination of sub-effective doses of glibenclamide as a katp channel blocker and cromakalim,as an opener of these channels,they were co-administrated with the sub-effective and effective doses of baclofen,respectively. results baclofen at dose 1 mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20 mg/kg). co-administration of gelibenclamide sub-effective dose (1 mg/kg) with baclofen (0.1 mg/kg) showed a synergistic antidepressant-like effect in the fst. also,sub-effective dose of cromakalim (0.1 mg/kg) inhibited the antidepressant-like effect of baclofen (1 mg/kg) in the fst. all aforementioned treatments had not any impact on the locomotor movement of mice in oft. conclusions our study for the first time revealed that antidepressant-like effect of baclofen on mice is katp-dependent,and baclofen seems that exert this effect by blocking the katp channels. © 2016