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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/R1375    most recent 00284.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Horn, C. C. Articles by Norgren, R. PubMed PubMed Citation Articles by Horn, C. C. Articles by Norgren, R.

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Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat

¹Monell Chemical Senses Center, Philadelphia, Pennsylvania; ²Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania; ³University of Pittsburgh Cancer Institute, Biobehavioral Medicine in Oncology Program; Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition; and Department of Anesthesiology, Pittsburgh, Pennsylvania

Submitted May 21, 2009 ; accepted in final form August 24, 2009

Anticancer agents, such as cisplatin, stimulate nausea, vomiting, and behaviors indicative of malaise. Rats and mice do not possess a vomiting response, and, therefore, in these species, the ingestion of kaolin clay (a pica response) has been used as an index of malaise. In the rat, cisplatin-induced kaolin intake is inhibited by antiemetic treatments. In addition, cisplatin activates vagal afferent fibers in the gut, and kaolin intake induced by cisplatin is largely dependent on an intact vagus. Nevertheless, little is known about the brain pathways controlling pica. We investigated the role of the lateral parabrachial nucleus (lPBN), a major visceral afferent link between the hindbrain and forebrain, in cisplatin-induced c-Fos expression and pica. Injection of cisplatin (6 mg/kg ip) produced c-Fos expression in the ventrolateral (external) lPBN, a region receiving viscerosensory input. In rats with bilateral ibotenic acid lPBN lesions, cisplatin treatment substantially increased kaolin intake compared with controls (30 g vs. 5 g, respectively, over 24 h). Food intake was reduced by cisplatin treatment and by apomorphine, an emetic agent that acts centrally. Unlike cisplatin, however, apomorphine stimulated kaolin intake to a similar degree in both the lesioned and control rats, suggesting that lPBN damage neither produces nonspecific effects nor enhances malaise in general. These data suggest that lPBN-lesioned animals not only demonstrate pica after cisplatin treatment, but, in fact, show an exaggerated response that is greatly in excess of any treatment known to produce kaolin intake in rats.

emesis; nausea; pica; vagus; anorexia