Serotonin depletion interferes with the weight-loss maintenance after central GLP-1R activation (A). While daily central EX4 injections in control rats led to a potent reduction of body weight, the weight loss impact of EX4 was markedly attenuated in rats depleted of serotonin by PCPA suggesting that intact serotonin synthesis is needed for a full expression of EX4-induced weight loss. PCPA/VEH animals did not increase in weight. n = 3–6 per each treatment group. Activation of central GLP-1R ameliorated changes in serotonin receptor genes in the hypothalamus induced by food restriction (B) and also increased serotonin turnover in the hypothalamus (C). *p < 0.05, **p < 0.01, ***p < 0.005, ****p < 0.001 compared to vehicle-treated rats. #p < 0.05, ##p < 0.01, ###p < 0.005 compared to pair-fed rats.