CP-94,253: A selective serotonin(1B) (5-HT(1B)) agonist that promotes satiety

Abstract

The selective 5-HT(1B) agonist CP-94,253 (3-(1,2,5,6-tetrahydro-4- pyridyl)-5-propoxypyrrolo[3,2-b] pyridine) (5-40 μmol/kg) reduced the intake of both pellets and a 10% solution of sucrose (ID50 = 12.5 and 22.8 μmol/kg, respectively) in mildly deprived rats. Time-sampled observations revealed that CP-94,253 terminated feeding earlier; without disrupting the continuity of feeding. CP-94,253 increased standing but did not promote resting during satiation. Microstructural analysis of licking indicated that CP-94,253 decreased the frequency, but not the size, of bursts and clusters of licks without altering oral motor efficiency. The peripherally acting 5- HT(1B) agonist, CP-93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2- b]pyrid-5-one) had no effect on food intake. These results imply that CP- 94,253 probes a role for central 5-HT(1B) receptors in the regulation of meal size and duration, but that recruitment of other 5-HT receptor subtypes may be needed for the full expression of satiety.