Effects of short term low dose melatonin and ketamine on depressive behavior and BDNF expression in rats with chronic stress depression

In a rat model of depression induced by chronic unpredictable mild stress, melatonin produced antidepressant-like effects comparable to those of ketamine. Rats exposed to 42 days of stress showed depressive-like behavior, indicated by reduced sucrose preference and increased immobility time in the forced swim test. After 14 days of treatment, both melatonin and ketamine significantly decreased immobility time and increased the number of BDNF-positive cells in the prefrontal cortex compared to stressed controls. Melatonin also increased BDNF cell counts more than ketamine did. However, only ketamine, not melatonin, significantly raised GluR1 cell counts. These findings suggest melatonin's antidepressant action may involve upregulation of BDNF.

Study at a glance

Abstract

Objective To evaluate the antidepressant action of melatonin in stress model of depression and the effects of the melatonin on depressive-like behavior. Methods Forty male Wistar rats were randomly divided into four groups(n=10): controls group (CON), chronic unpredictable mild stress group(CUS), chronic unpredictable mild stress group + melatonin group(CUS+ MT) and chronic unpredictable mild stress group + ketamine group(CUS+ KET). The rats in CUS group, CUS+ MT group and CUS+ KET group were given different stress stimulation for 42 days to establish the chronic mild unpredictable stress animal model.Sucrose preference experiments was used to detect the depression model and the level of depression was tested by forced swim test.The influence of Short-term low doses of melatonin on the level of BDNF and GluR1 in the prefrontal cortex, was detected by immunohistochemistry(IHC) on 58 day after the start of the experiment. Results (1) The CUS showed depressant-like behavior, and the percent sucrose uptake scores and the cumulative immobility time of the CUS group were decreased significantly(P<0.05). (2) After injection melatonin 14 d, the cumulative immobility time of CUS+ MT group((60.70±18.56)s) and CUS+ KET group((56.43±20.46)s) were decreased significantly in comparison to the CUS group(146.34±34.10)s). It was observed a highly significant (P<0.05) decrease of and up-regulation of the BDNF cells in CUS+ MT group((1 328.99±282.46)/mm2) and CUS+ KET group((1 224.76±116.53)/mm2) in comparison to the CUS group, the number of BDNF cells in CUS+ MT group was increased significantly in comparison to the CUS+ KET group; (3) After administration drug 14 days, the number of GluR1 cells of CUS+ KET((807.82±153.25)/mm2) but not CUS+ MT((632±156.34)mm2) significantly increased compared with CUS((807.82±193.25)/mm2). Conclusion The results indicate that the melatonin induce an antidepressant-like action like ketamine.The antidepressant effects of melatonin may be related with the level of BNDF. Key words: Melatonin; Ketamine; Depression; Chronic unpredictable mild stress; Rat