| First Author | Bruschetta G | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 2 | Pages | 108267 |
| PubMed ID | 33053350 | Mgi Jnum | J:300072 |
| Mgi Id | MGI:6489005 | Doi | 10.1016/j.celrep.2020.108267 |
| Citation | Bruschetta G, et al. (2020) MC4R Signaling in Dorsal Raphe Nucleus Controls Feeding, Anxiety, and Depression. Cell Rep 33(2):108267 |
| abstractText | Major depressive disorder is associated with weight loss and decreased appetite; however, the signaling that connects these conditions is unclear. Here, we show that MC4R signaling in the dorsal raphe nucleus (DRN) affects feeding, anxiety, and depression. DRN infusion of alpha-MSH decreases DRN neuronal activation and feeding. DRN MC4R is expressed in GABAergic PRCP-producing neurons. DRN selective knockdown of PRCP (Prcp(DRNKD)), an enzyme inactivating alpha-MSH, decreases feeding and DRN neuronal activation. Interestingly, Prcp(DRNKD) mice present lower DRN serotonin levels and depressive-like behavior. Similarly, PRCP-ablated MC4R mice (Prcp(MC4RKO)) show metabolic and behavioral phenotypes comparable to those of Prcp(DRNKD) mice. Selective PRCP re-expression in DRN MC4R neurons of Prcp(MC4RKO) mice partially reverses feeding, while fully restoring mood behaviors. Chemogenetic inhibition of DRN MC4R neurons induces anxiety, depression, and reduced feeding, whereas chemogenetic activation reverses these effects. Our results indicate that MC4R signaling in DRN plays a role in feeding, anxiety, and depression. |
