RT Journal Article
T1 Lack of Ovarian Secretions Reverts the Anabolic Action of Olanzapine in Female Rats.
A1 Skrede, Silje
A1 Gonzalez-Garcia, Ismael
A1 Martins, Luis
A1 Berge, Rolf Kristian
A1 Nogueiras, Ruben
A1 Tena-Sempere, Manuel
A1 Mellgren, Gunnar
A1 Steen, Vidar Martin
A1 Lopez, Miguel
A1 Fernø, Johan
K1 antipsychotics
K1 energy expenditure
K1 estradiol
K1 weight gain
AB 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. 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. 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. 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.
PB Oxford University Press
YR 2017
FD 2017-08-08
LK http://hdl.handle.net/10668/11671
UL http://hdl.handle.net/10668/11671
LA en
NO Skrede S, González-García I, Martins L, Berge RK, Nogueiras R, Tena-Sempere M, et al. Lack of Ovarian Secretions Reverts the Anabolic Action of Olanzapine in Female Rats. Int J Neuropsychopharmacol. 2017 Dec 1;20(12):1005-1012.
DS RISalud
RD Apr 11, 2025