5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding.

ABSTRACT: Obesity is primarily a consequence of consuming calories beyond energetic requirements, but underpinning drivers have not been fully defined. 5-Hydroxytryptamine (5-HT) neurons in the dorsal Raphe nucleus (5-HT^DRN) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HT^DRN to hypothalamic arcuate nucleus (5-HT^DRN → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT_2C and 5-HT_1B receptors, whereas activation of 5-HT^DRN to ventral tegmental area (5-HT^DRN → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT_2C receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HT^DRN neurons via inhibiting their responsiveness to inhibitory GABAergic inputs; non-hunger-driven feeding activates VTA-projecting 5-HT^DRN neurons through reducing a potassium outward current. Thus, our results support a model whereby parallel circuits modulate feeding behavior either in response to hunger or to hunger-independent cues.

SUBMITTER: He Y 

PROVIDER: S-EPMC8776930 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature