5-HT1A receptor activation is necessary for 5-MeODMT-dependent potentiation of feeding inhibition.
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.
Duvvuri
Vikas
V
Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804, United States.
Risbrough
Victoria B
VB
Kaye
Walter H
WH
Geyer
Mark A
MA
D000818:Animals; D003627:Data Interpretation, Statistical; D003975:Diazepam / Q000494:pharmacology; D004777:Environment; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D006993:Hypnotics and Sedatives; D008732:Methoxydimethyltryptamines; D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D003975:Diazepam