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Naunyn Schmiedebergs Arch Pharmacol. 2019 Mar 4. doi: 10.1007/s00210-019-01636-z. [Epub ahead of print]

Evaluation of the pharmacological involvement of ATP-sensitive potassium (KATP) channels in the antidepressant-like effects of topiramate on mice.

Author information

1
Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
2
Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box13145-784, Tehran, Iran.
3
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
4
Anesthesiology Department, Tehran University of Medical Sciences, Tehran, Iran.
5
University of Virginia, School of Medicine, Charlottesville, VA, USA.
6
Mayo Clinic Alix School of Medicine, Rochester, MN, USA.
7
Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box13145-784, Tehran, Iran. dehpoura@sina.tums.ac.ir.
8
Tehran University of Medical Sciences, Tehran, Iran. dehpoura@sina.tums.ac.ir.

Abstract

Acute doses of topiramate (TPM) have been shown to reduce immobility time in the mice forced swimming test (FST) through inhibition of the nitric oxide (NO) pathway. Adenosine triphosphate-sensitive potassium (KATP) channels are known to have an active role in depression. This study investigates the potential participation of KATP channels in the antidepressant-like effect of TPM through the stimulatory effects of NO. FST and tail suspension tests (TST) were applied to adult male mice for assessment of the antidepressant-like activity of TPM. Different doses of glibenclamide and cromakalim were also applied in order to investigate the involvement of KATP channels. Fluoxetine was used as a positive control for evaluation of antidepressant-like effects. In addition, each animal's locomotor activity was evaluated by the open-field test (OFT). TPM (30 mg/kg intraperitoneal (i.p.)) had a significant reductive effect on the immobility behavior similar to fluoxetine (20 mg/kg). Co-administration of sub-effective doses of glibenclamide (1 mg/kg i.p.) and TPM (10 mg/kg i.p.) led to significant synergistic effects in FST and TST. Additionally, the results showed that administration of the sub-effective dose of cromakalim (0.1 and 0.3 mg/kg i.p.) blocked the antidepressant-like effects of TPM (30 mg/kg i.p.) in both tests. These interventions had no impact on the locomotor movement of mice in OFT. This study shows that the antidepressant-like activity of TPM may potentially be mediated by the blocking of the KATP channels.

KEYWORDS:

ATP-sensitive potassium channels; Depression; Forced swimming test; Mice; Tail suspension test; Topiramate

PMID:
30828738
DOI:
10.1007/s00210-019-01636-z

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