抄録
The mechanism of cisplatin, anti-cancer drug,-induced delayed emesis has not been resolved clearly yet. We supposed that dynorphin, an endogenous ligand of κ-opioid receptor, could be a candidate for substances relating to cisplatin-induced delayed emesis because it appears in the central nervous system by various noxious stimuli and also relates to feeding behavior. Firstly we established a model of cisplatin-induced delayed emesis by means of pica meaning a response that increases an intake of a non-nutritional diet such as kaolin after administration of toxic stimulus. Consequently the dose of 5 mg/kg body weight was considered to be a suitable dose for the experimental model. Following the behavioral experiment, we immunohistochemically examined the induction of dynorphin A in the area postrema (AP), which is the chemoreceptor trigger zone for emesis, at 24, 48 and 72 h after the administration of 5 mg/kg cisplatin. Dynorphin A accumulates in the neurosoma of the AP neurons gradually by cisplatin. The numbers of positive AP neurons at 48 and 72 h after the administration of cisplatin were significantly higher than those after the administration of the same volume of 0.9% NaCl. These findings suggest that dynorphin A is associated with cisplatin-induced delayed emesis. [J Physiol Sci. 2007;57 Suppl:S140]
