title: Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.
abstract: 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.
authors.affiliation: Department of Biobehavioral Health Sciences, School of Nursing, United States. Electronic address: bartd@nursing.upenn.edu.
authors.forename: Bart C
authors.initials: BC
authors.lastname: De Jonghe
authors.affiliation: Department of Biobehavioral Health Sciences, School of Nursing, United States.
authors.forename: Ruby A
authors.initials: RA
authors.lastname: Holland
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, United States; Department of Neuroscience, University of Pittsburgh, United States.
authors.forename: Diana R
authors.initials: DR
authors.lastname: Olivos
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, United States; Department of Neuroscience, University of Pittsburgh, United States.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Rupprecht
authors.affiliation: Department of Biological Sciences, Human and Evolutionary Biology Section, University of Southern California, United States.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kanoski
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, United States. Electronic address: hayesmr@mail.med.upenn.edu.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hayes
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D057967:Infusions, Intraventricular; D008297:Male; D009325:Nausea / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010842:Pica / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D052336:Proglucagon / Q000378:metabolism; D051381:Rats; D012249:Rhombencephalon / Q000187:drug effects* / Q000378:metabolism*; D017552:Solitary Nucleus / Q000378:metabolism
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; C083773:exendin (9-39); D052336:Proglucagon; D002945:Cisplatin
keywords: Chemotherapy; Emesis; GLP-1; Illness; Nausea; Vomiting