Role of 5-HT(3) Receptor on Food Intake in Fed and Fasted Mice

BACKGROUND: Many studies have shown that 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the regulation of feeding behavior. However, the relative contribution of 5-HT(3) receptor remains unclear. The present study was aimed to investigate the role of 5-HT(3) receptor in control of feeding behavior in fed and fasted mice. METHODOLOGY/PRINCIPAL FINDINGS: Food intake and expression of c-Fos, tyrosine hydroxylase (TH), proopiomelanocortin (POMC) and 5-HT in the brain were examined after acute treatment with 5-HT(3) receptor agonist SR-57227 alone or in combination with 5-HT(3) receptor antagonist ondansetron. Food intake was significantly inhibited within 3 h after acute treatment with SR 57227 in fasted mice but not fed mice, and this inhibition was blocked by ondansetron. Immunohistochemical study revealed that fasting-induced c-Fos expression was further enhanced by SR 57227 in the brainstem and the hypothalamus, and this enhancement was also blocked by ondansetron. Furthermore, the fasting-induced downregulation of POMC expression in the hypothalamus and the TH expression in the brain stem was blocked by SR 57227 in the fasted mice, and this effect of SR 57227 was also antagonized by ondansetron. CONCLUSION/SIGNIFICANCE: Taken together, our findings suggest that the effect of SR 57227 on the control of feeding behavior in fasted mice may be, at least partially, related to the c-Fos expression in hypothalamus and brain stem, as well as POMC system in the hypothalamus and the TH system in the brain stem.