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The acute effects of olanzapine on ghrelin secretion, CCK sensitivity, meal size, locomotor activity and body temperature

International Journal of Obesity volume 36, pages 254–261 (2012)Cite this article

Abstract

Objective:

Significant weight gain is a problematic side effect of treatment with the antipsychotic drug olanzapine (OLA). Previous studies in rats suggest that one of the contributing factors is an impairment in satiation that results in increased food intake. However, the mechanisms underlying this impairment in satiation remain largely unclear.

Methods and results:

In this study, we determined the effect of OLA on levels of leptin, insulin, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1, peptide YY and amylin in male rats that had received a fixed amount of food. OLA did not affect the secretion of any of these hormones, except for ghrelin levels, which were increased compared with controls. Furthermore, when ghrelin levels were determined in rats just before they received their meal, OLA caused a significant increase in ghrelin levels compared with controls, whereas OLA failed to affect baseline ghrelin levels. Next, we investigated the effect of OLA on the efficacy of CCK to reduce meal size. With coadministration, OLA pretreatment counteracted the reduction in meal size by CCK, although there was no significant interaction between the treatments. Finally, telemetry measurements revealed that acute OLA treatment causes a temporary decrease in both locomotor activity and body core temperature.

Conclusion:

Taken together, this study shows that acute injection of OLA selectively increases meal-related ghrelin secretion and this may partially underlie the impairment in satiation by OLA.

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Acknowledgements

This work was supported by TI Pharma project T2.105.

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Author notes

  1. S E la Fleur and R A H Adan: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands

    E M van der Zwaal, M Merkestein, Y K Lam, M A D Brans, M C M Luijendijk, S E la Fleur & R A H Adan

  2. TNO Quality of Life, Zeist, The Netherlands

    L I H Bok & E R Verheij

  3. Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    S E la Fleur

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Correspondence to R A H Adan.

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van der Zwaal, E., Merkestein, M., Lam, Y. et al. The acute effects of olanzapine on ghrelin secretion, CCK sensitivity, meal size, locomotor activity and body temperature. Int J Obes 36, 254–261 (2012). https://doi.org/10.1038/ijo.2011.97

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