Brain Fos expression induced by the chemotherapy agent cisplatin in the rat is partially dependent on an intact abdominal vagus

Anticancer agents such as cisplatin stimulate nausea, vomiting, and behaviors indicative of malaise. Rats and mice, and probably all rodents, do not possess a vomiting response, and their ingestion of kaolin clay (a pica response) has been used as an index of malaise. Similar to the action of cisplatin on emesis in vomiting species, in the rat cisplatin activates vagal afferent fibers, and cisplatin-induced kaolin intake is largely dependent on an intact abdominal vagus. Cisplatin also stimulates Fos expression in the rat brain in areas known to play a role in emesis in other species, but it is not known whether vagal input is required for this CNS activation. In the present study, rats were given abdominal vagotomy or sham operation to test the role of an intact vagus on cisplatin-induced Fos expression 6 h after injection with saline or cisplatin (6 mg/kg, ip). Cisplatin treatment produced Fos expression in the area postrema and multiple levels of the nucleus of the solitary tract (NTS) of sham-operated rats. Vagotomy reduced cisplatin-induced Fos expression in the caudal and middle levels of the NTS and central amygdala. Furthermore, cisplatin did not significantly alter Fos expression in the spinal cord (T8-T10) before or after vagotomy. These results suggest that a defined portion of cisplatin-induced Fos expression is dependent on vagal input, with a majority of this response determined by either direct action of cisplatin or humoral factors on the CNS. (C) 2009 Elsevier B.V. All rights reserved.