5-HT(2C) receptor activation inhibits appetitive and consummatory components of feeding and increases brain c-fos immunoreactivity in mice

Eur J Neurosci. 2007 May;25(10):3115-24. doi: 10.1111/j.1460-9568.2007.05567.x.

Abstract

5-Hydroxytryptamine (5-HT)(2C) and 5-HT(1B) receptors are implicated in the inhibitory modulation of feeding behaviour. However, their respective, and possibly different, roles have not been clearly identified because of a lack of selective 5-HT(2C) receptor agonists. Here, using the putative, selective 5-HT(2C) receptor agonist VER23779, we show that its effects on feeding are fully reversed by pretreatment with a selective 5-HT(2C) receptor antagonist, but unaffected by pretreatment with either a 5-HT(1B) or a 5-HT(2A) receptor antagonist. In mice eating a palatable mash, feeding ends earlier, inactivity is increased but the behavioural satiety sequence is preserved. In a second-order schedule of reinforcement with an initial, non-food-reinforced appetitive phase, VER23779 produces a much greater relative reduction in appetitive responding than the 5-HT(1B) receptor agonist CP-94,253. Increased c-fos immunoreactivity patterns following VER23779 also differ from those described for CP-94,253, in particular showing strong activation of the basolateral amygdala. The different behavioural consequences of 5-HT(2C) and 5-HT(1B) receptor activation may relate to the patterns of c-fos immunoreactivity. In particular, the basolateral amygdala may have a role in maintaining response in the appetitive phase of the second-order schedule and also be susceptible to serotonergic modulation through activation of 5-HT(2C) receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects
  • Amygdala / metabolism
  • Animals
  • Appetite / drug effects
  • Appetite / physiology*
  • Brain / drug effects
  • Brain / metabolism*
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology*
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Receptor, Serotonin, 5-HT1B / drug effects
  • Receptor, Serotonin, 5-HT1B / metabolism
  • Receptor, Serotonin, 5-HT2C / metabolism*
  • Satiety Response / drug effects
  • Satiety Response / physiology
  • Serotonin / metabolism*
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Proto-Oncogene Proteins c-fos
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin