ABSTRACT
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-HT3 receptor remains unclear. The present study was aimed to investigate the role of 5-HT3 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-HT3 receptor agonist SR-57227 alone or in combination with 5-HT3 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.
Subject(s)
Eating , Fasting/metabolism , Receptors, Serotonin, 5-HT3/metabolism , Adrenocorticotropic Hormone/metabolism , Animals , Brain Stem/drug effects , Brain Stem/metabolism , Corticosterone/metabolism , Eating/drug effects , Gene Expression Regulation, Enzymologic/drug effects , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , Mice , Piperidines/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Tyrosine 3-Monooxygenase/metabolismABSTRACT
Recent studies in vivo and vitro have shown that Fuzi polysaccharide has an antidepressant-like effect. Polysaccharide and total alkaloid are the two most important components of Fuzi. However, little is known about the antidepressant-like effect of Fuzi total alkaloid. To investigate the antidepressant-like effect of Fuzi total alkaloid, behavioral studies were performed in the open field test and forced swimming test. Repeated intragastric administration of Fuzi total alkaloid for 7 days (10 mg/kg) to normal mice decreased immobility time compared to the vehicle group. Furthermore, repeated administration of Fuzi total alkaloid (10 or 30 mg/kg) to ovariectomized mice also decreased immobility time in a dose-dependent manner. However, these antidepressant-like behavioral effects were not simply due to locomotor hyperactivity. Further experiments showed that Fuzi total alkaloid enhanced the ratio of phospho-CREB/CREB (cAMP response element-binding) and BDNF (brain-derived neurotrophic factor) protein level in the frontal cortex and hippocampus in ovariectomized mice but not in normal mice. These results indicate that the CREB-BDNF pathway may be involved in the antidepressant-like effect of Fuzi total alkaloid in ovariectomized mice.