α-MSH produced from the ARC induces CRF secretion by the MC4R-co-expressing neurons in the amygdala and the PVN. CRF mediates anxiety- and depression-related behaviors through the HPA axis. In the DRN, the activity status of MC4R neurons affects serotonin levels, indicating a potential (indirect) connection between MC4R and 5-HT neurons. Both α-MSH and γ-MSH can stimulate MC3R-expressing neurons in the VTA, increasing consumption of sucrose-rich food and inducing grooming and rearing behaviors. Finally, PRCP, the enzyme involved in the degradation of α-MSH, plays a role in the modulation of melanocortin signaling and thus in the regulation of feeding and mood in the DRN.