Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 296, Issue 4, Pages R902-R911Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.90952.2008
Keywords
emesis; palonosetron; serotonin type 3 receptor
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Funding
- National Institutes of Health [DK-065971, DC-000014]
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De Jonghe BC, Horn CC. Chemotherapy agent cisplatin induces 48-h Fos expression in the brain of a vomiting species, the house musk shrew (Suncus murinus). Am J Physiol Regul Integr Comp Physiol 296: R902-R911, 2009. First published February 18, 2009; doi:10.1152/ajpregu.90952.2008.-Cancer chemotherapy drugs, such as cisplatin, potently produce nausea and vomiting. Acute effects of these treatments are partly controlled by antiemetic drugs, but the delayed effects (>24 h), especially nausea, are more difficult to treat. It is unknown what brain pathways produce this delayed sickness. Our prior data show that brain Fos expression is increased for at least 48 h after cisplatin treatment in the rat, a nonvomiting species. Here, we extend these observations by using house musk shrews (Suncus murinus), a species with an emetic response. Compared with saline injection, cisplatin treatment (30 mg/kg ip) induced Fos expression in hindbrain areas known to play a role in the generation of emesis, the dorsal motor nucleus (DMN), the area postrema, and the nucleus of the solitary tract (NTS), for up to 48 h. Cisplatin also stimulated Fos expression in the parabrachial nucleus (PBN) of the midbrain and the central nucleus of the amygdala (CeA) for at least 48 h after treatment. When animals were pretreated with the antiemetic palonosetron, a long-term serotonin type 3 (5-HT3) receptor antagonist, cisplatin-induced Fos expression was significantly attenuated in the NTS, DMN, and CeA at 6 h but not at 48 h. These results indicate that cisplatin activates a neural system that includes the dorsal vagal complex and forebrain in the musk shrew, which is partially suppressed by a 5-HT3 receptor antagonist. Our findings suggest the existence of an extensive neural system that could be targeted to reduce nausea, vomiting, and malaise in cancer patients receiving chemotherapy.
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