[Abstract Title]. - Society for Neuroscience

Poster
284. Regulation of Food Intake and Body Weight: Integration of Peripheral Signals:
Systems
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 284.3/PP26
Topic: E.07.b. Integration of peripheral signals: Systems
Support: NIH-DK065971
NIH-DC000014
Title: Brain Fos expression in the musk shrew induced by an emetic dose of a cancer
chemotherapy agent
Authors: *B. C. DE JONGHE, C. C. HORN;
Monell Chem Senses Ctr., Philadelphia, PA
Abstract: Cancer chemotherapy drugs, such as cisplatin, are extremely potent for producing
nausea and vomiting. Acute effects of these treatments are partly controlled by using anti-emetic
drugs, but the delayed effects (>24 h), especially nausea, are much more difficult to treat. It is
unknown what brain pathways might be responsible for this delayed sickness. Previous data from
our laboratory indicates that brain Fos expression is increased in the hindbrain and forebrain for
at least 48 h after cisplatin treatment in the non-vomiting rat. Here we extend these observations
using house musk shrews, a species with an emetic response. Since the cytoarchitecture of the
musk shrew brain is relatively unknown, we used cresyl violet staining of the whole brain and
retrograde tracer staining of the dorsal motor nucleus to identify the location of
immunohistochemically labeled nuclei for Fos protein. We injected (i.p.) 30 mg/kg cisplatin or
saline control and euthanized animals at 6, 24, or 48 h to determine brain Fos expression.
Cisplatin induced Fos expression in the hindbrain for up to 48 h, however, the highest level of
Fos staining occurred at 6 h post injection and decreased over 48 h. Fos positive cells were most
abundant in the nucleus of the solitary tract (NTS), area postrema (AP), and the dorsal motor
nucleus (DMN). Cisplatin also stimulated Fos expression in the amygdala at all three time points.
These results indicate that cisplatin activates a neural system that includes the dorsal vagal
complex (NTS, AP, and DMN) and amygdala of the shrew, which parallels the effects of
cisplatin treatment in the rat. Our findings suggest neural systems that could be targeted to
reduce delayed nausea and vomiting in cancer patients receiving chemotherapy.
Disclosures: B.C. De Jonghe , NIH grant DK065971, DC000014, B. Research Grant (principal
investigator, collaborator or consultant and pending grants as well as grants already received);
C.C. Horn, NIH grant DK065971, B. Research Grant (principal investigator, collaborator or
consultant and pending grants as well as grants already received).