Psychopharmacology

, Volume 164, Issue 1, pp 49–60

5-HT1B receptors modulate components of satiety in the rat: behavioural and pharmacological analyses of the selective serotonin1B agonist CP-94,253

  • Michelle D. Lee
  • Guy A. Kennett
  • Colin T. Dourish
  • Peter G. Clifton
Original Investigation

DOI: 10.1007/s00213-002-1162-7

Cite this article as:
Lee, M.D., Kennett, G.A., Dourish, C.T. et al. Psychopharmacology (2002) 164: 49. doi:10.1007/s00213-002-1162-7

Abstract

Rationale. 5-HT1B receptors are thought to be one of the receptor subtypes that mediate the inhibitory control of serotonin on food intake and satiety.

Objective. To use the selective 5-HT1B receptor agonist, CP-94,253 as a probe of 5-HT1B receptor function in feeding behaviour, and to confirm the pharmacological selectivity of CP-94,253-induced hypophagia with a range of antagonists.

Methods. Dose-response functions for CP-94,253 (0, 1.25, 2.5, 5.0 mg/kg; IP) were determined in animals consuming wet mash in a 40-min test session during which time-sampled behavioural observations were collected to evaluate satiety sequences. A meal patterning study was carried out in a separate group of rats. The 5-HT1A antagonist WAY 100,635 (0, 1.0, 3.0 mg/kg; SC), the 5-HT1B/1D antagonist GR 127,935 (0, 3 mg/kg; IP), and the 5-HT1B antagonist SB 224289 (0, 2.5, 5.0 mg/kg; IP) were used to confirm that 5-HT1B receptor subtypes were responsible for the action of CP-94,253 on feeding behaviour.

Results. CP-94,253 (2.5 mg/kg) reduced food intake and preserved the satiety sequence in animals consuming a diet of mash. GR 127,935 (3.0 mg/kg) and SB 224289 (2.5 mg/kg), but not WAY 100,635, attenuated the hypophagic effect of the 5-HT1B agonist, and returned the changes in satiety sequence to control patterns. Meal patterning analyses indicated that CP-94,253 (2.5 mg/kg) reduced food intake through a decrease in meal size and duration in the absence of any alteration in the rate of eating. A hypodipsic action of CP-94,253 was also observed (2.5 and 5.0 mg/kg).

Conclusion. These findings imply that 5-HT1B receptors regulate discrete elements of satiety. We discuss the potential role of 5-HT1B agonists for the treatment of obesity.

Feeding Drinking Meal size Obesity CP-94,253 SB 224289 GR 127,935 WAY100,635

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Michelle D. Lee
    • 1
  • Guy A. Kennett
    • 2
  • Colin T. Dourish
    • 2
  • Peter G. Clifton
    • 1
  1. 1.Laboratory of Experimental Psychology, University of Sussex, Brighton, East Sussex, BN1 9QG, UK
  2. 2.Vernalis Research Ltd, Oakdene Court, 613 Reading Road, Winnersh, Wokingham, Berkshire, RG41 5UA, UK