Dysregulation of hypothalamic modulation in olanzapine treated male rats

Date

2016-11-03

Author

Sezlev-Bilecen, Deniz
AK, MEHMET
Yanık, Tülin

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

The mechanism of weight gain through application of olanzapine, a serotonin and dopamine receptor antagonist has not been fully understood. Weight gain and food intake are under the control of various neurohormones; POMC (proopiomelanocortin), CART (cocaine and amphetamine regulated transcript), AgRP (Agouti-related peptide) and NPY (neuropeptide Y) that are majorly synthesized and secreted from the arcuate nucleus (ARC) of hypothalamus. In this study, the alteration of the ARC neurohormone levels in rats were determined as one of the weight gain mechanisms. To understand the underlying mechanism of olanzapine-induced weight gain, the drug was orally administrated to healthy male Wistar rats for analysis of both the hypothalamic gene expression and peripheral levels of those candidate neuropeptides. In rats hypothalamic mRNA levels of NPY, AgRP and POMC decreased while CART levels did not show any alteration. Consistently, circulating levels of NPY, AgRP and alpha-MSH decreased significantly yet CART levels were also reduced. In conclusion, it may be presumed that the antagonistic effect of olanzapine on the ARC neurons might be the onset for a dysregulation of the neurohormones secretion which may cause weight gain during treatment. (C) 2016 Elsevier Inc. All rights reserved.

Subject Keywords

Biological Psychiatry, Pharmacology

URI

https://hdl.handle.net/11511/38621

Collections

Department of Biology, Article