Tonic regulation of satiety by 5-HT1B receptors in the mouse: converging evidence from behavioural and c-fos immunoreactivity studies

Activation of 5-HT1B receptors is thought to play an important role in the inhibitory influence of serotonin on feeding behaviour and body weight in mammals. Earlier studies have shown that 5-HT1B-knockout (KO) mice eat more and are heavier than wild-type (WT) controls and that the selective 5-HT1B receptor agonist CP-94,253 reduces food intake in food-deprived mice. Here we characterize the behavioural effects of both CP-94,253 and the selective 5-HT1B receptor antagonist SB224289 on feeding and other behaviours within the behavioural satiety sequence, and also report a c-fos mapping study using CP-94,253. CP-94,253 produced a dose-dependent suppression of food intake with a profile consistent with a selective effect on feeding behaviour. These effects were absent or reduced in 5-HT1B-KO mice and in WT mice pretreated with SB224289. SB224289 administered alone enhanced food intake consistent with impaired satiation; a similar effect was apparent in 5-HT1B-KO mice compared to WT. CP-94,253 induced c-fos in a range of structures previously implicated in the expression of feeding behaviour. These results suggest that the activation of 5-HT1B receptors is an important component of endogenous satiation mechanisms in the mouse