Therefore, in the present study, to determine whether 5-HT is critical for the weight loss induced by GLP-1 receptor activation in mice, we examined the effects of liraglutide on daily food intake and body weight over 4 days in mice treated with or without the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA) for 3 days. In addition, to evaluate the relationship between the acute anorexic effects of the GLP-1 receptor agonist and the expression of hypothalamic 5-HT2A receptors, we examined the effect of liraglutide on the expression of hypothalamic 5-HT2A and 5-HT2C receptors in mice, which are responsive to the administration of liraglutide. We further assessed whether 5-HT2A receptors are involved in the acute anorexic effects of liraglutide by examining the acute effects of liraglutide on food intake in mice pretreated with the high-affinity 5-HT2A agonist (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl) methylamine hydrobromide (TCB-2).