Additive antidepressant-like effects of fasting with imipramine via modulation of 5-HT2 receptors in the mice

作者:Li, Bingjin; Zhao, Jing; Lv, Jiayin; Tang, Fang; Liu, Lei; Sun, Zhihui; Wang, Liang; Siwela, Sibongile P.; Wang, Yinuo; Song, Yunong; Manchishi, Stephen M.*; Cui, Ranji
来源:Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2014, 48: 199-206.
DOI:10.1016/j.pnpbp.2013.08.015

摘要

Recently, studies show that intermittent fasting and caloric restriction may improve symptoms of depression. However, there is little scientific evidence regarding the literature on the antidepressant-like effects of acute fasting. The present study aims to investigate the antidepressant-like effects and its influence on brain levels of the transcription factor cAMP response element-binding protein (CREB) and its phosphorylated form (p-CREB) in different time periods of fasting mice. Furthermore, the additive antidepressant-like effects of fasting with imipramine and the possible involvement of the 5-HT2 receptors were examined. In the present study 9 h, but not 3 h and 18 h of fasting significantly reduced immobility time in the forced swimming test (FST) without alteration in locomotor activity in the open field test. 9 h fasting also enhanced the ratio of p-CREB/CREB in the frontal cortex and hippocampus. Co-administration of 9 h of fasting and imipramine (30 mg/kg, i.p) produced the additive antidepressant-like effects in the FST and increased the ratio of p-CREB/CREB. Meanwhile, the additive effects were partially reversed by treatment with a 5-HT2A/2C receptor agonist, (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) (5 mg/kg, s.c). Furthermore, the antidepressant-like effects of 9 h fasting was also blocked by DOI compared to the non-fasting control group. Serum corticosterone level, but not 5-HT and noradrenaline, was significantly increased in a time-dependent manner following different time periods of fasting. Taken together, these results suggest that acute fasting produces antidepressant-like effects via enhancement of the p-CREB/CREB ratio, and additive antidepressant-like effects of fasting with imipramine may be related to modulating 5-HT2 receptors.