The 5-HT1B receptor agonist CP-94,253 reduces food intake and preserves the behavioural satiety sequence

The 5-HT1B receptor has been proposed as a link in the relationship between serotonin and satiety. However, the anorexia induced by RU-24969, a 5-HT1A/1B agonist, has been shown to delay behaviours associated with the onset of satiety, increase the frequency of intake and increase some nonfeeding activities. CP-94,253 is a highly selective agonist at the 5-HT1B receptor site with less affinity for other receptor sites, and has been used in this study to determine if agonism of 5-HT1B receptor sites adjust the behavioural satiety sequence in a way consistent with satiety. The effects of an ED50 of dose of CP-94,253 (5.0 mg/kg, IP) on eating behaviour of the fasted rat were monitored. Temporal profiles of behaviour duration and frequency were generated. Food intake was reduced 57% by CP-94,253 (p < 0.0005). Analysis confirmed that CP-94,253 reduced rearing (p < 0.05) and increased resting (p < 0.05) but preserved the overall pattern of the satiety sequence. Increased locomotion was not significant and caused no gross disruption of the behavioural repertoire. Such changes are also produced by prefeeding. In a second experiment, RU-24969 (1.0 mg/kg, IP) reduced food intake by only 30% (p < 0.05) However, RU-24969 markedly disrupted the satiety sequence profile, which did not resemble the profile produced by prefeeding. RU-24969 presumably induces this disruption via a mechanism other than 5-HT1B activation. The use of CP-95,253 demonstrates that selective activation of 5-HT1B receptor sites is sufficient to reduce food intake and enhance satiety as represented by the behavioural satiety sequence.