The study on antidepressant effects of ketamine and its mechanism associated with the expression of mTOR and GluR1 in the hippocampus in rats

Objective To investigate the antidepressant effects of different doses of ketamine of rats undergoing the forced swimming test and to elucidate its potential underlying mechanisms.Methods Forty male Wistar rats weigh-ing 180 ～ 220 g were equally randomized into 4 groups(n = 10 each).The forced swimming test(FST) for 15 min was used to establish a rat depression model.On the 2rd day,animals received intraperitoneal injection of saline,ketamine 5 mg/kg,10 mg/kg,or 15 mg/kg,respectively.Thirty minutes later,the rat immobility time was recorded during addi-tional 5min FST.The hippocampus was harvested for determination of mammalian target of rapa-mycin(mTOR) and glutamate receptor 1(GluR1) levels.Results Compared with saline group(169 ± 12 s),rats receiving ketamine(136 ± 13 s,119 ± 12 s,or 95 ± 20 s) showed significant decrease in immobility during FST in a dose-dependent manner(P 0.05).Rats receiving ketamine showed significant increase in the expression of mTOR(group saline: 0.87 ± 0.11;group ketamine: 1.52 ± 0.19,2.36 ± 0.13,2.95 ± 0.22) and GluR1(group saline: 0.91 ± 0.07;group ketamine: 1.23 ± 0.11,1.45 ± 0.06,1.60 ± 0.13)in the hippocampus as compared with group C(P 0.05).Conclusion Ketamine ex-erts antidepressant effects probably through upregulation of mTOR and GluR1 in the rat hippocampus.