Cancer chemotherapy drugs, such as
cisplatin, are extremely potent for producing
nausea and
vomiting. The acute effects of these treatments are partly controlled using
anti-emetic drugs, but the delayed effects (>24 h), especially
nausea, are much more difficult to treat. Furthermore,
cisplatin induces a long-term (up to 48 h) increase in
pica in rats.
Pica is manifested as an increase in consumption of
kaolin (
clay) and is used as a measure of visceral sickness. It is unknown what brain pathways might be responsible for this sickness associated behavior. As a first attempt to define this neural system, rats were injected (i.p.) with 3, 6, or 10 mg/kg
cisplatin (doses reported to produce
pica) and sacrificed at 6, 24, or 48 h to determine brain Fos expression. The primary results indicate: 1) increasing the dose of
cisplatin increased the magnitude and duration of brain Fos expression, 2) most excitatory effects on hindbrain nucleus of the solitary tract (NTS) and area postrema (AP) Fos expression occurred within 24 h after
cisplatin injection, 3) 6 and 10 mg/kg
cisplatin treatment produced large increases in Fos expression in the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST), including 48 h after injection, and 4)
cisplatin treatment produced little effect on Fos expression in the paraventricular and supraoptic nuclei of the hypothalamus. These results indicate that
cisplatin activates a neural system that includes the dorsal vagal complex (NTS and AP), CeA, and BNST.