Tonic regulation of satiety by 5‐HT_1B receptors in the mouse: converging evidence from behavioural and c‐fos immunoreactivity studies?

Abstract

Activation of 5-HT(1B) 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-HT(1B)-knockout (KO) mice eat more and are heavier than wild-type (WT) controls and that the selective 5-HT(1B) 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-HT(1B) 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-HT(1B)-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-HT(1B)-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-HT(1B) receptors is an important component of endogenous satiation mechanisms in the mouse.

Serotonin 1B and 2C receptor interactions in the modulation of feeding behaviour in the mouse

“…Thus, the present studies, when taken together with data from earlier investigations of the effects of 5-HT 2C agonists following disruption of either 5-HT 1B receptor function or pharmacological blockade of 5-HT 1B receptors (Clifton et al 2003, Lee et al 2004a, clarify the relationship between 5-HT 1B and 5-HT 2C receptor stimulation in the modulation of feeding behaviour in mice. 5-HT 2C receptor activation induces hypophagia in mice that has the broad characteristic of enhanced satiation rather than being the result of behavioural disruption (Hewitt et al 2002).…”

“…Administration of the selective 5-HT 1B receptor agonist, CP-94,253, reduces food intake and advances the behavioural satiety sequence in rats (Halford and Blundell 1996) and mice (Lee et al 2004a) as well as producing a dose-related decrease in intake of both food pellets and sucrose solutions in rats (Lee and Simansky 1997). In addition, the mixed 5-HT 1A/1B receptor agonist RU24969 reduces feeding in mice (Lucas et al 1998) and rats (Simansky and Vaidya 1990;Kitchener and Dourish 1994), as well as increasing c-fos immunoreactivity expression in the paraventricular nucleus of the hypothalamus, the central amygdaloid nucleus and in the bed nucleus of the stria terminalis (Lucas et al 1998).…”

Serotonin Activates the Hypothalamic-Pituitary-Adrenal Axis via Serotonin 2C Receptor Stimulation

“…Of note, the 5-HT 1D/1B R agonist CP94253 significantly induced FOS-IR in the PVH (Lee et al, 2004). Although not investigated here, it is possible that mCPP may also influence CRH activity indirectly through action at PVH 5-HT 1D Rs.…”

Serotonin controlling feeding and satiety

“…These and other findings suggest that activation of 5-HT1B receptors located in the PVN is sufficient but not necessary to induce satiety [4]. The selective 5-HT1B agonist CP-94,253 stimulated c-fos immunoreactivity in the PVN and the ventromedial nucleus (VMN) and in various other brain structures including hindbrain structures after satiating doses, suggesting the involvement of extrahypothalamic receptors in the 5-HT1B mediation of satiety [97].…”