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Acta Veterinaria

The Journal of University of Belgrade

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CiteScore 2016: 0.65

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Antidepressant effects of an inverse agonist selective for α5 GABA-A receptors in the rat forced swim test

Janko Samardžić
  • Corresponding author
  • Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Belgrade, Dr Subotića 1, Belgrade, Serbia;
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Laslo Puškaš
  • Institute of Anatomy “Niko Miljanić”, Medical Faculty, University of Belgrade, Dr Subotića 4, Belgrade, Serbia;
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Miljana Obradović
  • Institute of Histology and Embriology, Medical Faculty, University of Belgrade, Višegradska 26, Belgrade, Serbia;
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  • De Gruyter OnlineGoogle Scholar
/ Dijana Lazić-Puškaš
  • Clinic for Psychiatric Diseases “Dr Laza Lazarevic”, Belgrade, Serbia and Faculty of Special Education and Rehabilitation, University of Belgrade, Visokog Stevana 5, Belgrade, Serbia
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Published Online: 2014-03-25 | DOI: https://doi.org/10.2478/acve-2014-0006


It has been shown in electrophysiological studies that the ligand L-655,708 possesses a binding selectivity and a moderate inverse agonist functional selectivity for α5-containing GABA-A receptors. The present study is aimed to investigate the antidepressant effects of the ligand L-655,708 in the forced swim test (FST) and its impact on locomotor activity in rats. The behavior of the animals was recorded with a digital camera, and the data were analyzed by one-way ANOVA, followed by Dunnett’s test. In FST, L-655,708 significantly decreased immobility time at a dose of 3 mg/kg after a single and repeated administration (p<0.05), exerting acute and chronic antidepressant effects. However, it did not induce significant differences in the time of struggling behavior during FST. Furthermore, L-655,708 did not show a significant effect on locomotor activity (p>0.05). These data suggest that negative modulation at GABA-A receptors containing the α5 subunit may produce antidepressant effects in rats. These effects were not confounded by locomotor influences.

Keywords: GABA-A receptor; Inverse agonist; Depression; Forced swim test; Locomotor activity.


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About the article

Published Online: 2014-03-25

Published in Print: 2014-03-01

Citation Information: Acta Veterinaria, Volume 64, Issue 1, Pages 52–60, ISSN (Online) 1820-7448, DOI: https://doi.org/10.2478/acve-2014-0006.

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