5-HT(2C) receptor activation inhibits appetitive and consummatory components of feeding and increases brain c-fos immunoreactivity in mice.
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.
Somerville
Elizabeth M
EM
School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.
Horwood
Julia M
JM
Lee
Michelle D
MD
Kennett
Guy A
GA
Clifton
Peter G
PG
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012528:Satiety Response / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016760:Proto-Oncogene Proteins c-fos; D044302:Receptor, Serotonin, 5-HT1B; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin