5-HT1A receptor activation is necessary for 5-MeODMT-dependent potentiation of feeding inhibition.
Vikas Duvvuri, Victoria B Risbrough, Walter H Kaye, Mark A Geyer
Pharmacology, biochemistry, and behavior September 1, 2009 DOI: 10.1016/j.pbb.2009.05.014 via PubMed
Summary
AI-generated from the abstractA translational model of anorexia nervosa (AN) was tested using a hyponeophagia assay in mice, where food-deprived animals showed increased latency to begin feeding in a novel, anxiety-provoking environment. The non-selective serotonin agonist 5-MeODMT potentiated feeding inhibition beyond that caused by the environment alone, indicating a drug-by-environment interaction. Blocking the 5-HT(1A) receptor with WAY100635 reversed this effect, supporting a necessary role for 5-HT(1A) receptor activation in feeding inhibition. The findings suggest a mechanistic link between elevated 5-HT(1A) receptor activity and restricting-type AN, with implications for the interplay between anxiety and appetite suppression.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | 5-MeODMT WAY100635 |
| Keywords | Anxiety stress Psychological distress Apprehension Food intake Appetite regulation |
| Citations | 7 |
| Key finding | 5-HT(1A) receptor activation is necessary for feeding inhibition in a mouse model of anorexia nervosa. |
Abstract
We propose a translational approach to the study of anorexia nervosa (AN) based on our human subject studies where there are characteristic elevations in 5-HT(1A) receptor binding, associated harm avoidance behaviors, reduced impulsivity, and comorbid anxiety disorders. Towards this goal, the hyponeophagia assay was implemented whereby food-deprived mice show increased latency to begin feeding in a novel, anxiogenic environment. The non-selective serotonin agonist, 5-MeODMT, potentiates feeding inhibition compared to the inhibition generated by the anxiogenic environment in a drug-by-environment interaction. Thus, using hyponeophagia in mice, it was possible to study the following key components of AN: anxiety; feeding inhibition; and a modulatory role of the serotonergic system. A major prediction of the proposed AN model is that 5-HT(1A) receptor activation is necessary for feeding inhibition. In support of this model, the 5-HT(1A) receptor antagonist, WAY100635, reverses the 5-MeODMT-dependent potentiation of feeding inhibition. Our findings hint at a mechanistic role for increased 5-HT(1A) receptor activation in restricting-type AN. Further implications for the interplay between anxiety and feeding inhibition in AN are discussed.