<abstract xmlns="http://www.w3.org/1999/xhtml"><p>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&lt;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.</p></abstract>

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.

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

Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Belgrade, Dr Subotića 1, Belgrade, Serbia;

Institute of Anatomy “Niko Miljanić”, Medical Faculty, University of Belgrade, Dr Subotića 4, Belgrade, Serbia;

Institute of Histology and Embriology, Medical Faculty, University of Belgrade, Višegradska 26, Belgrade, Serbia;

Clinic for Psychiatric Diseases “Dr Laza Lazarevic”, Belgrade, Serbia and Faculty of Special Education and Rehabilitation, University of Belgrade, Visokog Stevana 5, Belgrade, Serbia

Acta Veterinaria

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 (p0.05). 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.

It has been shown in electrophysiological studies that the ligand L-655,708 possesses a binding selectivity and a moderate inverse agonist functional...

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

Publicado en línea: 25 mar 2014

Páginas: 52 - 60

DOI: https://doi.org/10.2478/acve-2014-0006

Palabras clave
GABA-A receptor, Inverse agonist, Depression, Forced swim test, Locomotor activity.

This content is open access.

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

Publicado en línea: 25 mar 2014

Páginas: 52 - 60

DOI: https://doi.org/10.2478/acve-2014-0006

Palabras claveGABA-A receptor, Inverse agonist, Depression, Forced swim test, Locomotor activity.

This content is open access.

Palabras clave
GABA-A receptor, Inverse agonist, Depression, Forced swim test, Locomotor activity.