5-HT1B receptor knockout mice show a compensatory reduction in 5-HT2C receptor function

Clifton, Peter G, Lee, Michelle D, Somerville, Elizabeth M, Kennett, Guy A and Dourish, Colin T (2003) 5-HT1B receptor knockout mice show a compensatory reduction in 5-HT2C receptor function. European Journal of Neuroscience, 17 (1). pp. 185-190. ISSN 1460-9568

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Although null mutant (`knockout¿) mice have provided valuable animal models to complement traditional approaches to psychopharmacology, such animals may also show complex adaptations to the induced mutation. Here we demonstrate that serotonin1B (5-HT1B) receptor knockout (KO) mice show adaptations in serotonin2C (5-HT2C) receptor-mediated functions. They show smaller reductions in food intake and locomotor activity in response to administration of 5-HT2C receptor agonists that are not accounted for by altered drug disposition. These effects are not mimicked by pretreatment of wildtype (WT) mice with a 5-HT1B receptor antagonist showing that they result from a longer term adaptation to the loss of 5-HT1B receptor function and not from a short-term interaction between 5-HT1B- and 5-HT2C-mediated functions. In addition, we show that 5-HT1B receptor KO mice have a lowered hypothalamic c-fos response to the administration of 5-HT2C receptor agonists. These results demonstrate that compensatory adaptations to the constitutive loss of 5-HT1B receptors may be an important determinant of the altered response of 5-HT1B KO mice to a variety of pharmacological challenges.

Item Type: Article
Additional Information: E.M.Somerville supervised the neuroanatomical work and analysed c-fos results. E.M.Somerville co-authored the paper in collaboration with P.G.Clifton and M.D.Lee. This work uses studies at a number of levels (neuroantomical and behavioural) to demonstrate how lifelong loss of one receptor affects the function of other receptors for the same neurotransmitter.
Schools and Departments: School of Life Sciences > Neuroscience
Depositing User: Pete Clifton
Date Deposited: 06 Feb 2012 20:38
Last Modified: 26 Mar 2012 11:51
URI: http://sro.sussex.ac.uk/id/eprint/27103
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