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MC4R Signaling in Dorsal Raphe Nucleus Controls Feeding, Anxiety, and Depression.

Abstract：

: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 α-MSH decreases DRN neuronal activation and feeding. DRN MC4R is expressed in GABAergic PRCP-producing neurons. DRN selective knockdown of PRCP (PrcpDRNKD), an enzyme inactivating α-MSH, decreases feeding and DRN neuronal activation. Interestingly, PrcpDRNKD mice present lower DRN serotonin levels and depressive-like behavior. Similarly, PRCP-ablated MC4R mice (PrcpMC4RKO) show metabolic and behavioral phenotypes comparable to those of PrcpDRNKD mice. Selective PRCP re-expression in DRN MC4R neurons of PrcpMC4RKO 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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Bruschetta G,Jin S,Liu ZW,Kim JD,Diano S

doi

10.1016/j.celrep.2020.108267

subject

Has Abstract

pub_date

2020-10-13 00:00:00

pages

108267

issue

2

issn

2211-1247

pii

S2211-1247(20)31256-0

journal_volume

33

pub_type

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