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

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• 作者：Seyedeh Khadijeh Nazari^a ; Vahid Nikoui^b ; Sattar Ostadhadi^c ; ^d ; ^e ; Zahra Hadi Chegini^a ; Shahrbanoo Oryan^a ; Azam Bakhtiarian^c ; ^e ; ^{bakhtiar@tums.ac.ir" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Baclofen ; ATP-sensitive potassium channels (KATP) ; Forced swimming test ; Mice
• 刊名：Pharmacological Reports
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：68
• 期：6
• 页码：1214-1220
• 全文大小：1197 K

文摘

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 (K_ATP), in the present study we investigated the involvement of K_ATP channels in antidepressant-like effect of baclofen in the forced swimming test (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 K_ATP channels, after determination of sub-effective doses of glibenclamide as a K_ATP 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 K_ATP-dependent, and baclofen seems that exert this effect by blocking the K_ATP channels.