Cisplatin-induced long-term dynorphin A-immunoreactivity in cell somata of rat area postrema neurons

Neurosci Lett. 2007 Sep 7;424(2):122-6. doi: 10.1016/j.neulet.2007.07.044. Epub 2007 Aug 8.

Abstract

We evaluated long-term dynorphin A-immunoreactivity in the rat area postrema (AP) after the administration of cisplatin. First, rats were given 1, 5 and 10mg/kg body weight cisplatin (i.p.) and their behavior was monitored for 72h. We observed a delayed increase in pica 24-72h after injection, compared to the 24h before injection. We attributed this to the cisplatin injection. Pica was defined as an increase in the intake of non-nutritional matter such as kaolin. Administration of 1, 5 and 10mg/kg cisplatin led to an increase in kaolin intake on day 1. Administration of 5 and 10mg/kg of cisplatin led to decreased intake of laboratory chow (MF) on days 1-3, but 10mg/kg cisplatin causes an excessive aggravation of their condition. Following this behavioral experiment, we immunohistochemically examined the induction of dynorphin A in the AP at 24, 48 and 72h post-administration of 1 and 5mg/kg cisplatin. Administration of 5mg/kg cisplatin caused dynorphin A to accumulate gradually in the neurosoma of the AP neurons, and the numbers of positive AP neurosomata at 48 and 72h post-administration were higher than following an equal dosage of 0.9% NaCl. These findings suggest that dynorphin A increases in the central nervous system for a long time following administration, and causes certain behavioral and clinical changes, including those related to appetite and nausea.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Area Postrema / cytology*
  • Behavior, Animal / drug effects
  • Cell Count
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Dynorphins / metabolism*
  • Eating / drug effects
  • Gene Expression Regulation / drug effects
  • Kaolin / administration & dosage
  • Male
  • Neurons / cytology
  • Neurons / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Antineoplastic Agents
  • Kaolin
  • Dynorphins
  • Cisplatin