Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat.
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 ( approximately 30 g vs. approximately 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.
Horn
Charles C
CC
Monell Chemical Senses Center, Philadelphia, Pennsylvania 15213, USA. chorn@pitt.edu
De Jonghe
Bart C
BC
Matyas
Kathleen
K
Norgren
Ralph
R
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D001058:Apomorphine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004639:Emetics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007616:Kaolin / Q000378:metabolism*; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D010842:Pica / Q000139:chemically induced* / Q000378:metabolism; D011149:Pons / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000378:metabolism
D000970:Antineoplastic Agents; D004639:Emetics; D016760:Proto-Oncogene Proteins c-fos; D007616:Kaolin; D001058:Apomorphine; D002945:Cisplatin