Impacts of olanzapine coupled with or without metformin administration on the expression of cannabinoid and melanocortin receptors in rats

Jacob Alis, Aditya Kemal
Secondary generation antipsychotics (SGA) were lauded as an improvement over first generation antipsychotics (FGA) in terms of both efficacies and reduced metabolic side effects such as obesity and diabetic phenotypes (1). However, SGAs were still plagued by a plethora of aforementioned metabolic side effects, albeit at reduced severity compared to the FGAs. While the side effects of SGAs had been extensively investigated through different experiments, the exact mechanism of the SGAs on the metabolic disorders’ development had not been determined. In our experiment the impacts of olanzapine, a type of SGA known to cause non-classical obesity, was investigated through the expression levels of both genes and proteins of cannabinoid receptor 1 (CB1R) and melanocortin 3 receptor (MC3R), two proteins which had been implicated as important components in energy metabolisms (2,3). In this study, to further understand the underlying mechanism of olanzapine induced weight gain, the drug was orally administrated to ten healthy Wistar-rats and then they were treated with metformin, which was known as anti-diabetic drug administered along with olanzapine, in various times. Next, the hypothalamic gene expressionś and protein levels of those candidate genes were analyzed with RT-PCR and Western-blot analyses, respectively. While CB1R’s gene expression was apparently not affected, MC3R’s gene expressions were decreased in animals administered only with olanzapine, with a marked increase in animals administered with olanzapine coupled by metformin. The gene expression results of MC3R were complemented by the decreases detected in protein levels of MC3R from olanzapine-affected animals; along with marked recovery of protein expressions in animals administered by both olanzapine and metformin together. These results might serve as another clue in elucidating the exact mechanisms of SGAs on the development of metabolic disorders which would serve as another step in the developments of better antipsychotics in terms of both higher efficacies and lower side effects. 


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Citation Formats
A. K. Jacob Alis, “Impacts of olanzapine coupled with or without metformin administration on the expression of cannabinoid and melanocortin receptors in rats,” M.S. - Master of Science, Middle East Technical University, 2017.