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

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• 作者：Bingjin Li ; Jing Zhao ; Jiayin Lv ; Fang Tang ; Lei liu ; Zhihui Sun ; Liang Wang ; Sibongile P. Siwela ; Yinuo Wang ; Yunong Song ; Stephen M. Manchishi ; Ranji Cui
• 关键词：ANOVA ; analysis of variance ; 5-HT ; serotonin ; FST ; forced swimming test ; i.p ; intraperitoneal ; NMDA ; N-methyl-d-aspartate ; DOI ; (± ; )-1-(2 ; 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride ; OFT ; open field test ; FST ; forced swimming test ; CREB ; cAMP response element-binding protein ; p- CREB ; phosphorylated cAMP response element-binding protein ; s.c ; subcutaneous ; BDNF ; brain derived neurotrophic factor
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：3 January, 2014
• 年：2014
• 卷：48
• 期：Complete
• 页码：199-206
• 全文大小：497 K

文摘

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-HT_2A/2C receptor agonist, (卤)-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.