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


CONCLUSIONS
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.
Lee
Michelle D
MD
Laboratory of Experimental Psychology, University of Sussex, Brighton, East Sussex, BN1 9QG, UK. michelle@biols.susx.ac.uk
Kennett
Guy A
GA
Dourish
Colin T
CT
Clifton
Peter G
PG
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000502:physiology*; D012528:Satiety Response / Q000187:drug effects* / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
C097067:CP 94253; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists