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

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Abstract

Rationale

To examine the functional relationship between 5-HT1B receptors (5-HT1B-R) and 5-HT2C receptors (5-HT2C-R) in the control of food intake.

Objectives

To compare the hypophagic effect of the 5-HT2C/1B-R agonist m-chlorophenylpiperazine (mCPP), with that of the selective 5-HT1B-R agonist CP-94,253 in both wildtype (WT) and 5-HT2C 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-HT2C KO mice using the behavioural satiety sequence paradigm. The effects of pre-treatment with the selective 5-HT2C-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-HT2C/1B receptor agonist mCPP and the selective 5-HT1B receptor agonist CP-94,253 both suppressed food intake in WT mice. 5-HT2C 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-HT2C KO mice, but this effect was absent in 5-HT2C KO mice who were given CP-94,253. Data from WT mice, who were pre-treated with the 5-HT2C receptor antagonist SB 242,084 and then challenged with either mCPP or CP-94,253, were similar to those obtained from 5-HT2C KO mice.

Conclusions

5-HT2C-R and 5-HT1B-R activation are each sufficient to induce a hypophagic response. However, concurrent 5-HT2C-R inactivation can potentiate the hypophagic response to 5-HT1B-R activation, consistent with an inhibitory role for the 5-HT2C-R in behaviour mediated by the activation of other 5-HT receptors. These results also confirm that 5-HT1B-R activation alone cannot account for the hyperactive response of 5-HT2C KO mice to mCPP.

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Acknowledgements

The authors gratefully acknowledge Dr. Laurence Tecott of UCSF for kindly donating the original breeding stock of 5-HT2C knockout mice; Dr. N. Carey and A. Kalli of Vernalis Research Ltd for genotyping; and Linda Penfold for her excellent care of our animals. This research was funded by a University of Sussex graduate teaching assistantship with additional funding from Vernalis Research Ltd (GD) and by a BBSRC LINK project grant 85/LKD12007 (MDL).

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Authors and Affiliations

  1. Department of Psychology, Sussex University, Brighton, BN1 9QG, UK

    G. L. Dalton, M. D. Lee & P. G. Clifton

  2. Vernalis Research Ltd., Wokingham, RG41 5UA, UK

    G. A. Kennett & C. T. Dourish

  3. Department of Psychiatry, School of Medicine, University of British Columbia, Detwiller Pavilion, 2255 Wesbrook Mall, V6T 1Z4, Vancouver, BC, Canada

    G. L. Dalton

  4. Department of Psychology, University of Wales Swansea, Singleton Park, Swansea, SA2 8PP, UK

    M. D. Lee

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  1. G. L. Dalton
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  2. M. D. Lee
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  5. P. G. Clifton
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Correspondence to P. G. Clifton.

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Dalton, G.L., Lee, M.D., Kennett, G.A. et al. Serotonin 1B and 2C receptor interactions in the modulation of feeding behaviour in the mouse. Psychopharmacology 185, 45–57 (2006). https://doi.org/10.1007/s00213-005-0212-3

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  • DOI: https://doi.org/10.1007/s00213-005-0212-3

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