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Hyperphagia and increased meal size are responsible for weight gain in rats treated sub-chronically with olanzapine

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Abstract

Rationale

Atypical antipsychotic-induced weight gain is a significant impediment in the treatment of schizophrenia.

Objectives

In a putative model of antipsychotic drug-induced weight gain, we investigated the effects of sub-chronic olanzapine on body weight, meal patterns, the expression of genes encoding for hypothalamic feeding-related neuropeptides and the contribution of hyperphagia to olanzapine-induced weight gain in rats.

Materials and methods

In experiment 1, female rats received either olanzapine (1 mg/kg, p.o.) or vehicle, twice daily for 7 days, while meal patterns were recorded. At the end of the treatment regimen, we measured the levels of hypothalamic messenger RNAs (mRNAs) encoding neuropeptide-Y (NPY), hypocretin/orexin (HCRT), melanin concentrating hormone and pro-opiomelanocortin. NPY and HCRT mRNA levels were also assessed in a separate cohort of female rats treated acutely with olanzapine (1 mg/kg, p.o.). In experiment 2, we investigated the effect of a pair-feeding paradigm on sub-chronic (1 mg/kg, p.o.) olanzapine-induced weight gain.

Results

In experiment 1, sub-chronic olanzapine increased body weight, food intake and meal size. Hypothalamic neuropeptide mRNA levels were unchanged after both acute and sub-chronic olanzapine treatment. In experiment 2, the restriction of food intake to the level of vehicle-treated controls abolished the sub-chronic olanzapine-induced increase in body weight.

Conclusions

Hyperphagia mediated by drug-induced impairments in satiety (as evidenced by increased meal size) is a key requirement for olanzapine-induced weight gain in this paradigm. However, olanzapine-induced hyperphagia and weight gain may not be mediated via alterations in the expression of the feeding-related hypothalamic neuropeptides examined in this study.

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Acknowledgements

The authors would like to thank Elena Korneeva and Peter Reed for their technical assistance. ND was supported by a BBSRC CASE studentship with GlaxoSmithKline PLC.

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Authors and Affiliations

  1. Department of Psychology, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK

    Nima Davoodi & Peter G. Clifton

  2. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline PLC, New Frontiers Science Park, Harlow, Essex, CM19 5AW, UK

    Mikhail Kalinichev

  3. Sussex Centre for Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK

    Sergei A. Korneev

Authors
  1. Nima Davoodi
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  2. Mikhail Kalinichev
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  3. Sergei A. Korneev
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  4. Peter G. Clifton
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Correspondence to Peter G. Clifton.

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Davoodi, N., Kalinichev, M., Korneev, S.A. et al. Hyperphagia and increased meal size are responsible for weight gain in rats treated sub-chronically with olanzapine. Psychopharmacology 203, 693–702 (2009). https://doi.org/10.1007/s00213-008-1415-1

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  • DOI: https://doi.org/10.1007/s00213-008-1415-1

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