Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea

Nov 3, 2015Physiology & behavior

Role of hindbrain GLP-1 receptors in cisplatin-related loss of appetite and nausea

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Abstract

Hindbrain GLP-1 receptor blockade attenuates anorexia, body weight reduction, and pica in rats following cisplatin chemotherapy during the delayed phase.

Cisplatin chemotherapy induces nausea, anorexia, and body weight loss in rats more than 24 hours after treatment.
Blockade of hindbrain GLP-1 receptors reduces these symptoms in the delayed phase of chemotherapy-induced nausea.
Cisplatin treatment leads to increased activation of GLP-1-producing neurons in a specific brain region associated with appetite regulation.
The findings suggest that the GLP-1 system may play a role in chemotherapy-induced nausea and related feeding behaviors.

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While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (<24 h) phase following treatment, the anorexia, nausea, fatigue, and other illness-type behaviors during the delayed phase (>24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments.

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Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea

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