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Possible Involvement of Atp-Sensitive Potassium Channels in the Antidepressant-Like Effects of Gabapentin in Mouse Forced Swimming Test Publisher Pubmed



Ostadhadi S1, 2 ; Akbarian R2, 3 ; Norouzijavidan A1 ; Nikoui V4 ; Zolfaghari S5 ; Chamanara M1, 6 ; Dehpour AR2, 3
Authors
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Authors Affiliations
  1. 1. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Tissue Engineering and Applied Cell Sciences, Iran University of Medical Sciences, Iran
  6. 6. Department of Pharmacology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran

Source: Canadian Journal of Physiology and Pharmacology Published:2017


Abstract

Gabapentin as an anticonvulsant drug also has beneficial effects in treatment of depression. Previously, we showed that acute administration of gabapentin produced an antidepressant-like effect in the mouse forced swimming test (FST) by a mechanism that involves the inhibition of nitric oxide (NO). 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 gabapentin. Gabapentin at different doses (5-10 mg/kg) and fluoxetine (20 mg/kg) were administrated by intraperitoneal route, 60 and 30 min, respectively, before the test. To clarify the probable involvement of KATP channels, mice were pretreated with KATP channel inhibitor or opener. Gabapentin at dose 10 mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20 mg/kg). Co-administration of subeffective dose (1 mg/kg) of glibenclamide (inhibitor of KATP channels) with gabapentin (3 mg/kg) showed a synergistic antidepressant-like effect. Also, subeffective dose of cromakalim (opener of KATP channels, 0.1 mg/kg) inhibited the antidepressant-like effect of gabapentin (10 mg/kg). None of the treatments had any impact on the locomotor movement. Our study, for the first time, revealed that antidepressant-like effect of gabapentin in mice is mediated by blocking the KATP channels. © 2017, Canadian Science Publishing. All rights reserved.
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