5-HT1B receptors modulate the feeding inhibitory effects of enterostatin

Abstract

Serotonin (5-HT) is considered to play an important role in control of appetite. Enterostatin has been shown to alter 5-HT release in the brain, and non-specific 5-HT antagonists blocked the anorectic response to icv enterostatin. The aim of this study was to further identify which 5-HT receptor subtype mediates the enterostatin feeding behavior and whether this effect occurs due to action in the PVN. Wild-type and 5-HT2C receptor-/- (KO) mice and normal Sprague-Dawley rats were used in these experiments. All animals were fed a high fat diet. Enterostatin (120 nmol, i.p.) reduced the intake of high fat diet in 5-HT2C receptor mutant mice (saline 4.54 +/- 0.47 kcal vs. Ent 2.53 +/- 0.76 kcal) 1 h after injection. A selective 5-HT1B antagonist (GR55526, 40 mg/kg body weight, i.p.) blocked the enterostatin hypophagic effects in these KO mice. Rats were implanted with cannulas into the amygdala and the ipsilateral PVN. The 5-HT receptor antagonists metergoline (non-specific receptor subtypes 1 and 2), or ritanserin (selective 2C), or GR55562 (selective l B) was injected into the PVN prior to enterostatin (0.01 nmol) injection into the amygdala. Enterostatin reduced food intake (saline: 5.80 +/- 0.59 g vs. enterostatin 3.47 +/- 0.56 g, P < 0.05 at l h). Pretreatment with either metergoline (10 nmol) or GR55526 (10 nmol) but not ritanserin (10 nmol) into the PVN attenuated the anorectic response to amygdala enterostatin. The data imply that the enterostatin anorectic response may be modulated by 5-HT1B receptors and that a neuronal pathway from the amygdala to the PVN regulates the enterostatin response through activation of 5-HTlB receptors in PVN.

Fig. 1

Effects of i.p. enterostatin (120 nmol) on the food intake of wild-type (WT; n = 5 male, n = 6 female) and 5-HT2C receptor knockout (KO; n = 9 male, n = 7 female) mice. Mice were food-deprived overnight. Data are expressed as means ± SEM of the cumulative intake (g). *P < 0.05 compared with respective saline vehicle group.

Fig. 2

Effects of 5-HT1B receptor antagonist GR55562 on hypophagia induced by i.p. enterostatin in 5-HT2C receptor knockout mice. *P < 0.05 compared with respective saline/saline (sal + sal) vehicle group.

Fig. 3

The effects of PVN injection of 5-HT receptors 1 and 2 antagonist metergoline on the hypophagia induced by amygdala injection of enterostatin. *P < 0.05 compared with respective vehicle + saline (V + S) control group.

Fig. 4

The effects of PVN injection of 5-HT1B antagonist GR55562 on the hypophagia induced by amygdala injection of enterostatin. *P < 0.05 compared with respective saline + saline (S + S) vehicle group.

Fig. 5

The effects of PVN injection of 5-HT2C antagonist ritanserin on the hypophagia induced by amygdala injection of enterostatin. *P < 0.05 compared with respective vehicle + saline (V + S) control group.