Dataset Information

Nucleus of the Solitary Tract Serotonin 5-HT_2C Receptors Modulate Food Intake.

ABSTRACT: To meet the challenge to human health posed by obesity, a better understanding of the regulation of feeding is essential. Medications targeting 5-hydroxytryptamine (5-HT; serotonin) 2C receptors (htr2c; 5-HT_2CR) improve obesity. Here we probed the functional significance of 5-HT_2CRs specifically within the brainstem nucleus of the solitary tract (5-HT_2CR^NTS) in feeding behavior. Selective activation of 5-HT_2CR^NTS decreased feeding and was sufficient to mediate acute food intake reductions elicited by the 5-HT_2CR agonist obesity medication lorcaserin. Similar to pro-opiomelanocortin neurons expressed within the hypothalamic arcuate nucleus (POMC^ARC), a subset of POMC^NTS neurons co-expressed 5-HT_2CRs and were activated by 5-HT_2CR agonists. Knockdown of POMC^NTS prevented the acute appetite-suppressive effect of lorcaserin, whereas POMC^ARC knockdown prevented the full anorectic effect. These data identify 5-HT_2CR^NTS as a sufficient subpopulation of 5-HT_2CRs in reducing food intake when activated and reveal that 5-HT_2CR agonist obesity medications require POMC within the NTS and ARC to reduce food intake.

SUBMITTER: D'Agostino G

PROVIDER: S-EPMC6371983 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake.

D'Agostino Giuseppe G Lyons David D Cristiano Claudia C Lettieri Miriam M Olarte-Sanchez Cristian C Burke Luke K LK Greenwald-Yarnell Megan M Cansell Celine C Doslikova Barbora B Georgescu Teodora T Martinez de Morentin Pablo Blanco PB Myers Martin G MG Rochford Justin J JJ Heisler Lora K LK

Cell metabolism 20180823 4

To meet the challenge to human health posed by obesity, a better understanding of the regulation of feeding is essential. Medications targeting 5-hydroxytryptamine (5-HT; serotonin) 2C receptors (htr2c; 5-HT2CR) improve obesity. Here we probed the functional significance of 5-HT2CRs specifically within the brainstem nucleus of the solitary tract (5-HT2CRNTS) in feeding behavior. Selective activation of 5-HT2CRNTS decreased feeding ...[more]

PMID: 30146485

Similar Datasets

Project description:The serotonin 5HT2c receptor has been widely implicated in the pathophysiology of alcohol use disorder (AUD), particularly alcohol seeking and the affective consequences of chronic alcohol consumption. However, little is known about the brain sites in which 5HT2c exerts its effects on specific alcohol-related behaviors, especially in females. Here, we investigated the effects of site-specific manipulation of the 5HT2c receptor system in the BNST on operant alcohol self-administration behaviors in adult mice of both sexes, including the acquisition and maintenance of fixed-ratio responding, motivation for alcohol (progressive ratio), and quinine-adulterated responding for alcohol on a fixed-ratio schedule (punished alcohol seeking). Knockdown of 5HT2c in the BNST did not affect the acquisition or maintenance of operant alcohol self-administration, nor did it affect progressive ratio responding for alcohol. This manipulation had only a subtle effect on responding for quinine alcohol selectively in females. On the other hand, chemogenetic inhibition of BNST 5HT2c-containing neurons (BNST5HT2c) increased operant alcohol self-administration behavior in both sexes on day 2, but not day 9, of testing. It also increased operant responding for 1000 μM quinine-adulterated alcohol selectively in males. Importantly, chemogenetic inhibition of BNST5HT2c did not alter operant sucrose responding or motivation for sucrose in either sex. We then performed cell-type specific anterograde tracing, which revealed that BNST5HT2c project to similar regions in males and females, many of which have been previously implicated in AUD. We next used chemogenetics and quantification of the immediate early gene cFos to characterize the functional influence of BNST5HT2c inhibition on vlPAG activity. We show that chemogenetic inhibition of BNST5HT2c reduces vlPAG cFos in both sexes, but that this reduction is more robust in males. Together these findings suggest that BNST5HT2c neurons, and to a small extent the BNST 5HT2c receptor, serve to promote aversive responses to alcohol consumption, potentially through sex-dependent disinhibition of vlPAG neurons.

Dataset Information

Nucleus of the Solitary Tract Serotonin 5-HT_2C Receptors Modulate Food Intake.

Publications

Nucleus of the Solitary Tract Serotonin 5-HT<sub>2C</sub> Receptors Modulate Food Intake.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake.

Publications

Nucleus of the Solitary Tract Serotonin 5-HT&lt;sub&gt;2C&lt;/sub&gt; Receptors Modulate Food Intake.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Nucleus of the Solitary Tract Serotonin 5-HT_2C Receptors Modulate Food Intake.

Nucleus of the Solitary Tract Serotonin 5-HT<sub>2C</sub> Receptors Modulate Food Intake.