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Int J Neuropsychopharmacol. 2017 Dec 1;20(12):1005-1012. doi: 10.1093/ijnp/pyx073.

Lack of Ovarian Secretions Reverts the Anabolic Action of Olanzapine in Female Rats.

Author information

1
The Norwegian Centre for Mental Disorders Research and the K.G. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; Department of Physiology, Research Center of Molecular Medicine and Chronic Diseases, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain; The Lipid Research Group, Section for Medical Biochemistry, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica/Hospital Reina Sofía, Córdoba, Spain; KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; Section of Clinical Pharmacology, Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.

Abstract

Background:

Olanzapine is an orexigenic antipsychotic drug associated with serious metabolic adverse effects in humans. Development of valid rodent models for antipsychotic-induced metabolic adverse effects is hampered by the fact that such effects occur in females only. Estradiol is a predominant female hormone that regulates energy balance. We hypothesized that the female-specific hyperphagia and weight gain induced by olanzapine in the rat are dependent on the presence of estrogens.

Methods:

Female sham-operated or ovariectomized rats were treated with a single injection of olanzapine depot formulation. Food intake, body weight, plasma lipids, lipogenic gene expression, energy expenditure, and thermogenic markers including brown adipose tissue uncoupling protein 1 protein levels were measured. Olanzapine was also administered to ovariectomized rats receiving estradiol replacement via the subcutaneous (peripheral) or intracerebroventricular route.

Results:

Orexigenic effects of olanzapine were lost in ovariectomized female rats. Ovariectomized rats treated with olanzapine had less pronounced weight gain than expected from their food intake. Accordingly, brown adipose tissue temperature and protein levels of uncoupling protein 1 were elevated. Replacement in ovariectomized rats with either peripherally or centrally administered estradiol reduced food intake and body weight. Cotreatment with olanzapine blocked the anorexigenic effect of peripheral, but not central estradiol.

Conclusions:

Our results indicate that the ovarian hormone estradiol plays an important role in olanzapine-induced hyperphagia in female rats and pinpoint the complex effects of olanzapine on the balance between energy intake and thermogenesis.

KEYWORDS:

antipsychotics; energy expenditure; estradiol; weight gain

PMID:
29020342
PMCID:
PMC5716078
DOI:
10.1093/ijnp/pyx073
[Indexed for MEDLINE]
Free PMC Article

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