Tonic regulation of satiety by 5-HT receptors in the mouse: converging evidence from behavioural and c-fos immunoreactivity studies?
Activation of 5-HT(1B) receptors is thought to play an important role in the inhibitory influence of serotonin on feeding behaviour and body weight in mammals. Earlier studies have shown that 5-HT(1B)-knockout (KO) mice eat more and are heavier than wild-type (WT) controls and that the selective 5-HT(1B) receptor agonist CP-94,253 reduces food intake in food-deprived mice. Here we characterize the behavioural effects of both CP-94,253 and the selective 5-HT(1B) receptor antagonist SB224289 on feeding and other behaviours within the behavioural satiety sequence, and also report a c-fos mapping study using CP-94,253. CP-94,253 produced a dose-dependent suppression of food intake with a profile consistent with a selective effect on feeding behaviour. These effects were absent or reduced in 5-HT(1B)-KO mice and in WT mice pretreated with SB224289. SB224289 administered alone enhanced food intake consistent with impaired satiation; a similar effect was apparent in 5-HT(1B)-KO mice compared to WT. CP-94,253 induced c-fos in a range of structures previously implicated in the expression of feeding behaviour. These results suggest that the activation of 5-HT(1B) receptors is an important component of endogenous satiation mechanisms in the mouse.
Lee
Michelle D
MD
School of Life Sciences, University of Sussex, Brighton, Sussex BN1 9QG, UK.
Somerville
Elizabeth M
EM
Kennett
Guy A
GA
Dourish
Colin T
CT
Clifton
Peter G
PG
D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D013997:Time Factors
C097067:CP 94253; D010069:Oxadiazoles; D010879:Piperazines; D010881:Piperidones; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; C108518:SB 22489G; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; C090701:GR 127935