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

- Acute fasting reduces immobility time in the forced swimming test.
- Acute fasting enhances the p-CREB/CREB ratio in the hippocampus and frontal cortex.
- Acute fasting with imipramine produces the additive antidepressant-like effects.
- The additive effects of acute fasting with imipramine were partially reversed by DOI.

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.