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Psychopharmacology (Berl). 2002 Oct;164(1):49-60. Epub 2002 Jul 19.

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

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  • 1Laboratory of Experimental Psychology, University of Sussex, Brighton, East Sussex, BN1 9QG, UK. michelle@biols.susx.ac.uk

Abstract

RATIONALE:

5-HT(1B) 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-HT(1B) receptor agonist, CP-94,253 as a probe of 5-HT(1B) 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-HT(1A) antagonist WAY 100,635 (0, 1.0, 3.0 mg/kg; SC), the 5-HT(1B/1D)antagonist GR 127,935 (0, 3 mg/kg; IP), and the 5-HT(1B) antagonist SB 224289 (0, 2.5, 5.0 mg/kg; IP) were used to confirm that 5-HT(1B) 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-HT(1B) 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-HT(1B) receptors regulate discrete elements of satiety. We discuss the potential role of 5-HT(1B) agonists for the treatment of obesity.

PMID:
12373419
[PubMed - indexed for MEDLINE]
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