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Olanzapine-induced weight gain in the rat: role of 5-HT2C and histamine H1 receptors

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Abstract

Introduction

Substantial increases in body weight can be induced by several antipsychotic drugs, most notably olanzapine and clozapine. Antagonism at certain receptors, particularly 5-HT2C and histamine H1 receptors, is implicated in this effect.

Materials and methods

We have investigated the contribution of effects at these receptors to olanzapine-induced weight gain occurring over 5 days following daily intraperitoneal drug injections in groups of eight female rats.

Results

Olanzapine (2 mg/kg) and the 5-HT2C antagonist SB 243213 (1 mg/kg), but not the histamine H1 antagonist mepyramine (1 mg/kg), produced significant increases in percentage body weight above vehicle; olanzapine showed a significantly greater effect than SB 243213. Haloperidol (0.1 mg/kg) alone or with mepyramine had no significant effects on weight gain, while with SB 243213 and with both SB 243213 and mepyramine, it showed olanzapine-like increases in weight.

Conclusion

These results suggest that 5-HT2C receptor antagonism or inverse agonism, in the presence of D2 receptor antagonism, may contribute to olanzapine-induced weight gain.

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Acknowledgments

We would like to thank GlaxoSmithKline for the kind donation of olanzapine and SB 243213.

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Authors and Affiliations

  1. Department of Psychiatry, Queen’s University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast, BT9 7BL, UK

    Shona L. Kirk & Gavin P. Reynolds

  2. Bradford School of Pharmacy, University of Bradford, Bradford, BD7 1DP, UK

    John Glazebrook, Ben Grayson & Joanna C. Neill

Authors
  1. Shona L. Kirk
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  2. John Glazebrook
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  3. Ben Grayson
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  4. Joanna C. Neill
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  5. Gavin P. Reynolds
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Correspondence to Gavin P. Reynolds.

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Kirk, S.L., Glazebrook, J., Grayson, B. et al. Olanzapine-induced weight gain in the rat: role of 5-HT2C and histamine H1 receptors. Psychopharmacology 207, 119–125 (2009). https://doi.org/10.1007/s00213-009-1639-8

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  • DOI: https://doi.org/10.1007/s00213-009-1639-8

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