Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effects of gabapentin in mouse forced swimming test.
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 KATPchannels 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 KATPchannels, mice were pretreated with KATPchannel 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 KATPchannels) with gabapentin (3 mg/kg) showed a synergistic antidepressant-like effect. Also, subeffective dose of cromakalim (opener of KATPchannels, 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 KATPchannels.
a Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.|b Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Sattar
S
Ostadhadi
b Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.|c Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Reyhaneh
R
Akbarian
a Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Abbas
A
Norouzi-Javidan
d Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
Vahid
V
Nikoui
e Department of Tissue Engineering and Applied Cell Sciences, Iran University of Medical Sciences, Iran.
Samira
S
Zolfaghari
b Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.|f Department of Pharmacology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran.
Mohsen
M
Chamanara
b Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.|c Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Ahmad-Reza
AR
Dehpour
D000588:Amines / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D000077206:Gabapentin; D046353:Immobility Response, Tonic / Q000187:drug effects; D054086:KATP Channels / Q000378:metabolism*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D013550:Swimming / Q000523:psychology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology* / Q000627:therapeutic use
D000588:Amines; D000928:Antidepressive Agents; D003509:Cyclohexanecarboxylic Acids; D054086:KATP Channels; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
ATP-sensitive potassium channels (KATP); canaux potassiques sensibles à l’ATP (KATP); forced swimming test; gabapentin; gabapentine; mice; souris; test de nage forcée