ABSTRACT
Objective Accumulating evidence has demonstrated that the sub-anesthetic dose of ketamine exerts rapid and ro-bust antidepressant-like effects though its action mechanisms are not yet fully understood .The aim of this study was to investigate the role of gamma-aminobutyric acid ( GABA) in the antidepressant effects of ketamine . Methods Thirty-two male Wistar rats were e-qually randomized into four groups: saline, ketamine, GABA, and GABA+ketamine.All the animals were implanted with a guide cannula into the lateral ventricle and on the eighth day after operation subjected to a 15 min forced swimming test (FST) for the estab-lishment of a depression model .At 24 h after modeling , the rats of the saline and ketamine groups were treated intracerebroventricularly with 2μL isotonic saline solution, and those of the GABA and GABA +ketamine groups with 50μg (2μL) GABA, followed by intrap-eritoneal administration of 1 mL saline in the former two groups and 10 mg/kg (1 mL) ketamine in the latter two groups 10 min later.At 30 min after treatment , the open field test ( OFT) was carried out for crossing and rearing scores and a 6-min FST was performed to re-cord the immobility time in the last 5 minutes.The content of GABA in the prefrontal cortex of the rats was measured following behav -ioral tests. Results The immobility time was significantly decreased in the ketamine group ([107.5 ±21.2]sec) as compared with the saline, GABA, and GABA+ketamine groups ([167.2 ±22.1], [159.8 ±17.5], and [143.8 ±22.1]sec) (P0.05).The level of GABA in the prefrontal cortex was remarkably lower in the ketamine group ([12.4 ±3.4]ng/mg prot) than in the saline, GABA, and GABA+ketamine groups ([23.3 ± 6.3], [27.3 ±5.7], and [18.0 ±5.4]ng/mg prot) (P0.05 ). Conclusion The antidepressant effects of ketamine are related to the decreased GABA level in the prefrontal cortex in rats receiving FST .