Nazari Seyedeh Khadijeh, Nikoui Vahid, Ostadhadi Sattar, Chegini Zahra Hadi, Oryan Shahrbanoo, Bakhtiarian Azam
Faculty of Biology Sciences, Kharazmi University, Tehran, Iran.
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
Pharmacol Rep. 2016 Dec;68(6):1214-1220. doi: 10.1016/j.pharep.2016.07.006. Epub 2016 Jul 22.
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), in the present study we investigated the involvement of K channels in antidepressant-like effect of baclofen in the forced swimming test (FST).
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 1mg/kg) and fluoxetine (20mg/kg) were administrated by intraperitoneal (ip) route, 30min before the FST or OFT. To clarify the probable involvement of K channels, after determination of sub-effective doses of glibenclamide as a K 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 1mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20mg/kg). Co-administration of gelibenclamide sub-effective dose (1mg/kg) with baclofen (0.1mg/kg) showed a synergistic antidepressant-like effect in the FST. Also, sub-effective dose of cromakalim (0.1mg/kg) inhibited the antidepressant-like effect of baclofen (1mg/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 K-dependent, and baclofen seems that exert this effect by blocking the K channels.
先前的研究证实，通过抑制L-精氨酸-一氧化氮（NO）途径用巴氯芬进行急性治疗可减少小鼠强迫游泳试验（FST）中的不动行为。考虑到NO参与三磷酸腺苷（ATP）敏感性钾通道（K），在本研究中，我们调查了K通道在巴氯芬强迫游泳试验（FST）中抗抑郁样作用中的参与情况。
在旷场试验（OFT）中评估运动行为后，应用FST评估巴氯芬对小鼠的抗抑郁样活性。在FST或OFT前30分钟，通过腹腔内（ip）途径给予不同剂量（0.1、0.3和1mg/kg）的巴氯芬和氟西汀（20mg/kg）。为了阐明K通道可能的参与情况，在确定作为K通道阻滞剂的格列本脲和作为这些通道开放剂的克罗卡林的亚有效剂量后，将它们分别与巴氯芬的亚有效和有效剂量共同给药。
1mg/kg剂量的巴氯芬显著降低了小鼠的不动行为，类似于氟西汀（20mg/kg）。格列本脲亚有效剂量（1mg/kg）与巴氯芬（0.1mg/kg）共同给药在FST中显示出协同抗抑郁样作用。此外，克罗卡林亚有效剂量（0.1mg/kg）在FST中抑制了巴氯芬（1mg/kg）的抗抑郁样作用。所有上述处理对OFT中小鼠的运动行为均无任何影响。
我们的研究首次表明，巴氯芬对小鼠的抗抑郁样作用依赖于K通道，并且巴氯芬似乎通过阻断K通道发挥这种作用。
