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.
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.
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.