title: Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effect of baclofen in mouse forced swimming test.
abstract: BACKGROUND
  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 (KATP), in the present study we investigated the involvement of KATPchannels 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 1mg/kg) and fluoxetine (20mg/kg) were administrated by intraperitoneal (ip) route, 30min before the FST or OFT. To clarify the probable involvement of KATPchannels, after determination of sub-effective doses of glibenclamide as a KATPchannel 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 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.
  
  
  CONCLUSIONS
  Our study for the first time revealed that antidepressant-like effect of baclofen on mice is KATP-dependent, and baclofen seems that exert this effect by blocking the KATPchannels.
authors.affiliation: Faculty of Biology Sciences, Kharazmi University, Tehran, Iran.
authors.forename: Seyedeh Khadijeh
authors.initials: SK
authors.lastname: Nazari
authors.affiliation: Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Nikoui
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sattar
authors.initials: S
authors.lastname: Ostadhadi
authors.affiliation: Faculty of Biology Sciences, Kharazmi University, Tehran, Iran.
authors.forename: Zahra Hadi
authors.initials: ZH
authors.lastname: Chegini
authors.affiliation: Faculty of Biology Sciences, Kharazmi University, Tehran, Iran.
authors.forename: Shahrbanoo
authors.initials: S
authors.lastname: Oryan
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: bakhtiar@tums.ac.ir.
authors.forename: Azam
authors.initials: A
authors.lastname: Bakhtiarian
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001418:Baclofen / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D007103:Immobilization / Q000379:methods / Q000523:psychology; D054086:KATP Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D008297:Male; D051379:Mice; D013550:Swimming / Q000502:physiology / Q000523:psychology*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D058786:GABA-B Receptor Agonists; D054086:KATP Channels; D001418:Baclofen
keywords: ATP-sensitive potassium channels (K(ATP)); Baclofen; Forced swimming test; Mice