University of Sussex
Browse

File(s) not publicly available

Reduced hypophagic effects of d-fenfluramine and the 5-HT2C receptor agonist mCPP in 5-HT1B receptor knockout mice

journal contribution
posted on 2023-06-07, 23:26 authored by Michelle D Lee, Elizabeth M Somerville, Guy A Kennett, Colin T Dourish, Pete CliftonPete Clifton
Rationale The possible role of compensatory changes in 5-HT2C receptors in the reduced hypophagic action of d-fenfluramine in 5-HT1B knockout (KO) mice was assessed by comparing their response to d-fenfluramine and the 5-HT2C receptor agonist mCPP. In addition we measured 5-HT2C/A receptor binding in 5-HT1B KO and wild-type (WT) mice and examined the effects of 5-HT1B receptor antagonists on d-fenfluramine-induced hypophagia in WT mice. Methods Hypophagic responses to d-fenfluramine (1¿30 mg/kg) and mCPP (1¿5.6 mg/kg) were measured using a behavioural satiety sequence paradigm. The effects of the 5-HT1B receptor antagonists GR 127,935 and SB 224289 in opposing the hypophagic action of d-fenfluramine were evaluated in WT mice. The binding of [3H]-mesulergine was compared in the brains of both mouse strains. Results The hypophagic effects of moderate doses of d-fenfluramine and mCPP were attenuated in 5-HT1B KO mice. Pretreatment of WT mice with the 5-HT1B/1D receptor antagonist GR 127,935, or food-deprived WT mice with the 5-HT1B receptor antagonist SB 224289, did not reproduce the reduction in sensitivity to the effects of d-fenfluramine on feeding behaviour observed in 5-HT1B KO mice. Estimates of 5-HT2C receptor binding were similar in 5-HT1B KO and WT mice Conclusions The hypophagic effect of d-fenfluramine in mice is unlikely to be mediated by the 5-HT1B receptor. Instead, the evidence suggests that an adaptive change in 5-HT2C receptor function occurs in 5-HT1B receptor KO mice and contributes to their reduced response to d-fenfluramine.

History

Publication status

  • Published

Journal

Psychopharmacology

ISSN

0033-3158

Issue

1

Volume

176

Page range

39-49

Pages

11.0

Department affiliated with

  • Neuroscience Publications

Notes

E.M.Somerville took the lead in the interpretation of the result of the binding study and co-authored the paper in collaboration with P.G.Clifton and M.D.Lee. This study explores the effects of knocking out one receptor on a second receptor for the same neurotransmitter using the analysis of behaviour and receptor binding.

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC