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

Rationale To examine the functional relationship between 5-HT 1B receptors (5-HT 1B -R) and 5-HT 2C receptors (5-HT 2C -R) in the control of food intake. Objectives To compare the hypophagic effect of the 5-HT 2C/1B -R agonist m -chlorophenylpiperazine (mCPP), with that of the selective 5-HT 1B -R agonist CP-94,253 in both wildtype (WT) and 5-HT 2C knockout (KO) mice. Methods The hypophagic effects of mCPP (1, 3 and 5.6 mg/kg) and CP-94,253 (5, 10 and 20 mg/kg) were assessed in WT and 5-HT 2C KO mice using the behavioural satiety sequence paradigm. The effects of pre-treatment with the selective 5-HT 2C -R antagonist SB 242,084 (0.5 and 1.5 mg/kg) were assessed in two groups of WT mice, with each group given only mCPP or CP-94,253. Results The 5-HT 2C/1B receptor agonist mCPP and the selective 5-HT 1B receptor agonist CP-94,253 both suppressed food intake in WT mice. 5-HT 2C KO mice were insensitive to the hypophagic effects of mCPP but were more sensitive to CP-94,253-induced hypophagia than WT controls. mCPP induced a significant increase in post-prandial activity in 5-HT 2C KO mice, but this effect was absent in 5-HT 2C KO mice who were given CP-94,253. Data from WT mice, who were pre-treated with the 5-HT 2C receptor antagonist SB 242,084 and then challenged with either mCPP or CP-94,253, were similar to those obtained from 5-HT 2C KO mice. Conclusions 5-HT 2C -R and 5-HT 1B -R activation are each sufficient to induce a hypophagic response. However, concurrent 5-HT 2C -R inactivation can potentiate the hypophagic response to 5-HT 1B -R activation, consistent with an inhibitory role for the 5-HT 2C -R in behaviour mediated by the activation of other 5-HT receptors. These results also confirm that 5-HT 1B -R activation alone cannot account for the hyperactive response of 5-HT 2C KO mice to mCPP.