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- Title
5-HT[sub 1B] receptors modulate components of satiety in the rat: behavioural and pharmacological analyses of the selective serotonin[sub 1B] agonist CP-94,253.
- Authors
Lee, Michelle D.; Kennett, Guy A.; Dourish, Colin T.; Clifton, Peter G.
- Abstract
Rationale: 5-HT[sub 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[sub 1B] receptor agonist, CP94,253 as a probe of 5-HT[sub 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 CP94,253 (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[sub 1A] antagonist WAY 100,635 (0, 1.0, 3.0 mg/kg; SC), the 5-HT[sub 1B/1D] antagonist GR 127,935 (0, 3 mg/kg; IP), and the 5-HT[sub 1B] antagonist SB 224289 (0, 2.5, 5.0 mg/kg; IP) were used to confirm that 5-HT[sub 1B] receptor subtypes were responsible for the action of CP94,253 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 5HT[sub 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 5HT[sub 1B] receptors regulate discrete elements of satiety. We discuss the potential role of 5-HT[sub 1B] agonists for the treatment of obesity.
- Subjects
SEROTONIN agonists; PHARMACOLOGY
- Publication
Psychopharmacology, 2002, Vol 164, Issue 1, p49
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-002-1162-7