Dysregulation of hypothalamic modulation in olanzapine treated male rats

Sezlev-Bilecen, Deniz
Yanık, Tülin
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.


Alterations of hypothalamic neuropeptides involved in food intake and appetite in olanzapine monotherapy
Sezlev, Deniz; Yanık, Tülin; Department of Biology (2012)
The mechanism of weight gain due to treatment with olanzapine, a serotonin receptor antagonist, has not been fully understood. Weight gain and food intake are under the control of neuropeptides/hormones, POMC (proopiomelanocortin), CART (cocaine and amphetamine regulated transcript), AgRP (Agouti-related peptide) and NPY (neuropeptide Y) that are synthesized and secreted from the arcuate nucleus (ARC) of hypothalamus. In this study, the altereration of the ARC neuropeptide/hormone levels both in humans and ...
Differential expressions and functions of phosphodiesterase enzymes in different regions of the rat heart
DERİCİ, MEHMET KÜRŞAT; SADİ, GÖKHAN; Cenik, Basar; Güray, Nülüfer Tülün; DEMİREL YILMAZ, EMİNE (Elsevier BV, 2019-02-05)
Phosphodiesterase enzymes (PDEs) are responsible for the adjustment of cyclic nucleotide levels. Alterations in PDE expressions in different tissues cause conflicts between functional and clinical effects of PDE inhibitors. Therefore, the aim of this study was to investigate the gene and protein expressions and the functional role of PDEs in atrium and ventricle of rat heart The expressions of PDEs were examined in cardiac intact tissues and enzymatically isolated cells. The effects of PDE1-5 inhibitors (vi...
Genotoxicity studies of tetrahydro-naphthalene-benzimidazole/thiazolidinedione as retinoid derivatives
Doğan, Tuğba; Ates-Alagoz, Zeynep; Buyukbingol, Erdem (2015-11-01)
Objective: Mutagenicity is an undesirable side effect of clinically prescribed drugs, thus raises the question of their potential carcinogenicity. Taking into account that nitro compounds are known for their genotoxicity, it will be considerable interest to assess the genotoxic activities of the benzimidazole/thiazolidinedione retinoid derivatives. For this reason, the present study reports the genotoxicity of previously synthesized benzimidazole/thiazolidinedione-retinoid derivatives (Ates-Alagoz and Buyuk...
Fluoxetine, not donepezil, reverses anhedonia, cognitive dysfunctions and hippocampal proteome changes during repeated social defeat exposure
Gottschalk, M. G.; Mortas, P.; Haman, M.; Özcan Kabasakal, Süreyya; Biemans, B.; Bahn, S. (Elsevier BV, 2018-01-01)
While anhedonia is considered a core symptom of major depressive disorder (MDD), less attention has been paid to cognitive dysfunctions. We evaluated the behavioural and molecular effects of a selective serotonin re-uptake inhibitor (SSRI, fluoxetine) and an acetylcholinesterase inhibitor (AChEI, donepezil) on emotional-cognitive endophenotypes of depression and the hippocampal proteome. A chronic social defeat (SD) procedure was followed up by "reminder" sessions of direct and indirect SD. Anhedonia-relate...
Interactions between G-protein Coupled Receptors and Ligand Gated Ion Channels (GPCR-LGIC COUPLING)
Son, Çağdaş Devrim(2014-9-30)
Dopamine receptors are members of G-protein coupled receptor superfamily. These receptors are the key point of dopaminergic system, which controls the regulation of memory, attention, food intake, endocrine regulation, psychomotor activity and positive reinforcement. To regulate so many critically important neurological events, dopamine receptors have complex interactions with other receptors and ion channels. In this study, a trimeric complex comprising D2 receptor -which is a subtype of dopamine receptors...
Citation Formats
D. Sezlev-Bilecen, M. AK, and T. Yanık, “Dysregulation of hypothalamic modulation in olanzapine treated male rats,” PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, pp. 103–107, 2016, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/38621.