ANTIDEPRESSANT EFFECTS OF AN INVERSE AGONIST SELECTIVE FOR alpha 5 GABA-A RECEPTORS IN THE RAT FORCED SWIM TEST

作者：Samardzic Janko^*; Pukas Laslo; Obradovic Miljana; Lazic Puskas Dijana; Obradovic I Dragan

来源：Acta Veterinaria-Beograd, 2014, 64(1): 52-60.

DOI：10.2478/acve-2014-0006

• GABA-A receptor
• Inverse agonist
• Depression
• Forced swim test
• Locomotor activity

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 alpha 5-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 alpha 5 subunit may produce antidepressant effects in rats. These effects were not confounded by locomotor influences.

• 出版日期2014