The mechanism of acute fasting-induced antidepressant-like effects in mice

Abstract

Acute fasting induced antidepressant-like effects. However, the exact brain region and mechanism of these actions are still largely unknown. Therefore, in this study the antidepressant-like effects of acute fasting on c-Fos expression and BDNF levels were investigated. Consistent with our previous findings, immobility time was remarkably shortened by 9 hrs fasting in the forced swimming test. Furthermore, these antidepressant-like effects of 9 fasting were inhibited by a 5-HT_2A/2C receptor agonist (±)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), and the effect of DOI was blocked by pretreatment with a selective 5-HT_2A receptor antagonist ketanserin. Immunohistochemical study has shown that c-Fos level was significantly increased by 9 hrs fasting in prefrontal cortex but not hippocampus and habenular. Fasting-induced c-Fos expression was further enhanced by DOI in prefrontal cortex, and these enhancements were inhibited by ketanserin. The increased BDNF levels by fasting were markedly inhibited by DOI in frontal cortex and hippocampus, and these effects of DOI on BDNF levels were also blocked by ketanserin. These findings suggest that the antidepressant-like effects of acute fasting may be exerted via 5-HT_2A receptor and particularly sensitive to neural activity in the prefrontal cortex. Furthermore, these antidepressant-like effects are also mediated by CREB and BDNF pathway in hippocampus and frontal cortex. Therefore, fasting may be potentially helpful against depression.

Keywords: BDNF; 5-HT; Depression; c-Fos; fasting.

Figure 1

Effects of acute fasting on immobility time, normalize to control, in forced swimming test. (A) Effects of 9 and 18 hrs fasting on immobility time (n = 7–8); (B) Effects of 9 hrs fasting and DOI on immobility time (n = 8). Columns represent mean ± S.E.M. ^# P < 0.05 as compared with control group (non‐fasting); *P < 0.05 as compared with fasting control group; CON: control; DOI: (±)‐1‐(2, 5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane hydrochloride, 5 mg/kg, i.p.; IMI: imipramine, 30 mg/kg, i.p.; KET: ketanserin tartrate, 5 mg/kg, i.p.

Figure 2

C‐Fos expression in habenular region. (A) Representative photomicrographs of c‐Fos staining in habenular; (B) Quantification of c‐Fos expression in five experimental groups. Columns represent mean ± S.E.M. (n = 8). ^# P < 0.05 as compared with control group (non‐fasting); **P < 0.01 as compared with fasting control group; CON: control; DOI: (±)‐1‐(2, 5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane hydrochloride, 5 mg/kg, i.p.; IMI: imipramine, 30 mg/kg, i.p.; KET: ketanserin tartrate, 5 mg/kg, i.p.

Figure 3

C‐Fos expression in Cg1,PrL and IL region of prefrontal cortex. Cg1: (A); PrL: (B); IL: (C). (A) Representative photomicrographs of c‐Fos staining; (B) Quantification of c‐Fos expression in five experimental groups.^# P < 0.05; ^## P < 0.01 as compared with control group (non‐fasting); *P < 0.05; **P < 0.01 as compared with fasting control group; CON: control; DOI: (±)‐1‐(2, 5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane hydrochloride, 5 mg/kg, i.p.; IMI: imipramine, 30 mg/kg, i.p.; KET: ketanserin tartrate, 5 mg/kg, i.p.

Figure 4

C‐Fos expression in CA1, CA2, CA3 and dentate gyrus region of hippocampus. (A) Representative photomicrographs of c‐Fos staining;(B) Quantification of c‐Fos expression in five experimental groups. Columns represent mean ± S.E.M. (n = 8). ^# P < 0.05 as compared with control group (non‐fasting); *P < 0.05 as compared with fasting control group; CON: control; DOI: (±)‐1‐(2, 5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane hydrochloride, 5 mg/kg, i.p.; IMI: imipramine, 30 mg/kg, i.p.; KET: ketanserin tartrate, 5 mg/kg, i.p.

Figure 5

Effects of 9 hrs fasting on BDNF levels, normalize to control, in brain. (A) Effects of 9 hrs fasting on BDNF levels in frontal cortex. (B) Effects of 9 hrs fasting and DOI on immobility time. Columns represent mean ± S.E.M. (n = 7). ^# P < 0.05 as compared with control group (non‐fasting); *P < 0.05 as compared with fasting control group; CON: control; DOI: (±)‐1‐(2, 5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane hydrochloride, 5 mg/kg, i.p.; IMI: imipramine, 30 mg/kg, i.p.; KET: ketanserin tartrate, 5 mg/kg, i.p.