Hypophagia induced by hindbrain serotonin is mediated through central GLP-1 signaling and involves 5-HT2C and 5-HT3 receptor activation

Apr 9, 2019Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Reduced eating caused by serotonin in the hindbrain involves brain GLP-1 signaling and activation of 5-HT2C and 5-HT3 receptors

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Administration of exogenous hindbrain serotonin (5-HT) alters food intake and body weight changes in rats through central GLP-1 receptor signaling.

5-HT interacts with the central GLP-1 system, influencing both satiation and malaise responses.
Anatomical evidence indicates the presence of serotonin receptors on GLP-1-producing neurons in the brain.
The reduction in food intake (hypophagia) from activating serotonin receptors depends on GLP-1 signaling.
5-HT3 receptors, but not 5-HT2C receptors, are necessary for the anorectic effects triggered by the interoceptive stressor LiCl.
These findings suggest a complex role of 5-HT in modulating food intake and stress responses through GLP-1 pathways.

AI simplified

The overlap in neurobiological circuitry mediating the physiological and behavioral response to satiation and noxious/stressful stimuli are not well understood. The interaction between serotonin (5-HT) and glucagon-like peptide-1 (GLP-1) could play a role as upstream effectors involved in mediating associations between anorectic and noxious/stressful stimuli. We hypothesize that 5-HT acts as an endogenous modulator of the central GLP-1 system to mediate satiation and malaise in rats. Here, we investigate whether interactions between central 5-HT and GLP-1 signaling are behaviorally and physiologically relevant for the control of food intake and pica (i.e., behavioral measure of malaise). Results show that the anorexia and body weight changes induced by administration of exogenous hindbrain 5-HT are dependent on central GLP-1 receptor signaling. Furthermore, anatomical evidence shows mRNA expression of 5-HT2C and 5-HT3 receptors on GLP-1-producing preproglucagon (PPG) neurons in the medial nucleus tractus solitarius by fluorescent in situ hybridization, suggesting that PPG neurons are likely to express both of these receptors. Behaviorally, the hypophagia induced by the pharmacological activation of both of these receptors is also dependent on GLP-1 signaling. Finally, 5-HT3, but not 5-HT2C receptors, are required for the anorectic effects of the interoceptive stressor LiCl, suggesting the hypophagia induced by these 5-HT receptors may be driven by different mechanisms. Our findings highlight 5-HT as a novel endogenous modulator of the central GLP-1 system and suggest that the central interaction between 5-HT and GLP-1 is involved in the control of food intake in rats.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗

Hypophagia induced by hindbrain serotonin is mediated through central GLP-1 signaling and involves 5-HT2C and 5-HT3 receptor activation

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief