Olanzapine administration reduces chemotherapy-induced body weight loss and pica in rats

Authors

• RB Jaime-Lara
• T Borner
• R Holland
• E Shaulson
• B Brooks
• BC De Jonghe

Abstract

Chemotherapy-Induced Nausea and Vomiting (CINV) is a prevalent adverse effect of chemotherapy, reducing quality of life and resulting in increase medical costs. Olanzapine has been added to cancer antiemetic guidelines due to its effectiveness in treating CINV. However, substantial knowledge-gaps regarding the pathophysiology of CINV and the biological basis of olanzapine’s effect on CINV exist. Thus, we conducted a literature review and identified potential biological mediators of olanzapine’s effects on CINV: ghrelin and serotonin signaling systems. Subsequently, we conducted a series of behavioral experiments to study olanzapine’s impact on chemotherapy-induced side effects in rats. Olanzapine decreased chemotherapy-induced weight loss and nausea. To test the effect of olanzapine on potential biological mediators of these chemotherapy-induced adverse effects, we assessed the effects of olanzapine on ghrelin and serotonin signaling systems. We found that olanzapine decreases the number of cisplatin-chemotherapy activated neurons in the hindbrain and determined olanzapine’s effect on chemotherapy-induced malaise is at least in part mediated by the hindbrain. We found olanzapine counteracts cisplatin-induced decreases in circulating ghrelin and central ghrelin receptor [GHSR] gene expression six hours post chemotherapy. We report olanzapine decreased serotonin 2C receptor [5-HT2C] gene expression in the hindbrain and the hypothalamus. These findings suggest that olanzapine may alleviate CINV by counteracting the effects of cisplatin on the hindbrain, ghrelin signaling, and 5-HT2C receptor gene expression in the hindbrain and hypothalamus. Future research should further define the role of these potential biological mediators and determine if alterations of ghrelin and 5-HT2C signaling are sufficient to help control CINV.

Scientific Focus Area: Cancer Biology

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