These results demonstrate that Ro 60-0175 is a useful probe of the importance of 5-HT2C activation in the control of food intake and support the hypothesis that activation of 5-HT2C receptors is a critical aspect of the hypophagic action of d-fenfluramine. The 5-HT2C receptor may prove to be a useful target in the development of clinically effective drugs for the treatment of obesity.
The selective 5-HT1B agonist CP-94,253 (3- (1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3, 2-b] pyridine) (5-40 mumol/kg) reduced the intake of both pellets and a 10% solution of sucrose (ID50 = 12.5 and 22.8 mumol/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-HT1B 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-HT1B 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.
These results suggest that the expression of caffeine conditioned flavour preferences are acutely sensitive to current motivational state, and a number of possible explanations are discussed.
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