5-HT1A receptor activation is necessary for 5-MeODMT-dependent potentiation of feeding inhibition

Pharmacol Biochem Behav. 2009 Sep;93(3):349-53. doi: 10.1016/j.pbb.2009.05.014. Epub 2009 May 31.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Data Interpretation, Statistical
  • Diazepam / pharmacology
  • Environment
  • Exploratory Behavior / drug effects
  • Fear / drug effects
  • Feeding Behavior / drug effects*
  • Hypnotics and Sedatives / pharmacology
  • Male
  • Methoxydimethyltryptamines / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Serotonin 5-HT1 Receptor Agonists*
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology*

Substances

  • Hypnotics and Sedatives
  • Methoxydimethyltryptamines
  • Piperazines
  • Pyridines
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • Diazepam