Reduced hypophagic effects of d-fenfluramine and the 5-HT2C receptor agonist mCPP in 5-HT1B receptor knockout mice.
Psychopharmacology (Berl)
; 176(1): 39-49, 2004 Oct.
Article
em En
| MEDLINE
| ID: mdl-15138762
ABSTRACT
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-HT(2C/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-HT(1B/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.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Saciação
/
Camundongos Knockout
/
Receptor 5-HT1B de Serotonina
/
Fenfluramina
/
Agonistas do Receptor 5-HT2 de Serotonina
País/Região como assunto:
Europa
Idioma:
En
Revista:
Psychopharmacology (Berl)
Ano de publicação:
2004
Tipo de documento:
Article