Authors: Michelle D Lee Elizabeth M Somerville Guy A Kennett Colin T Dourish Peter G Clifton
Publish Date: 2004/05/08
Volume: 176, Issue: 1, Pages: 39-49
Abstract
The possible role of compensatory changes in 5HT2C receptors in the reduced hypophagic action of dfenfluramine in 5HT1B knockout KO mice was assessed by comparing their response to dfenfluramine and the 5HT2C receptor agonist mCPP In addition we measured 5HT2C/A receptor binding in 5HT1B KO and wildtype WT mice and examined the effects of 5HT1B receptor antagonists on dfenfluramineinduced hypophagia in WT miceHypophagic responses to dfenfluramine 1–30 mg/kg and mCPP 1–56 mg/kg were measured using a behavioural satiety sequence paradigm The effects of the 5HT1B receptor antagonists GR 127935 and SB 224289 in opposing the hypophagic action of dfenfluramine were evaluated in WT mice The binding of 3Hmesulergine was compared in the brains of both mouse strainsThe hypophagic effects of moderate doses of dfenfluramine and mCPP were attenuated in 5HT1B KO mice Pretreatment of WT mice with the 5HT1B/1D receptor antagonist GR 127935 or fooddeprived WT mice with the 5HT1B receptor antagonist SB 224289 did not reproduce the reduction in sensitivity to the effects of dfenfluramine on feeding behaviour observed in 5HT1B KO mice Estimates of 5HT2C receptor binding were similar in 5HT1B KO and WT miceThe hypophagic effect of dfenfluramine in mice is unlikely to be mediated by the 5HT1B receptor Instead the evidence suggests that an adaptive change in 5HT2C receptor function occurs in 5HT1B receptor KO mice and contributes to their reduced response to dfenfluramine
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