Cisplatin-induced long-term dynorphin A-immunoreactivity in cell somata of rat area postrema neurons.
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.
Tsukamoto
Goichi
G
Department of Oral and Maxillofacial Surgery, Biopathological Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan. gtsuka@md.okayama-u.ac.jp
Ichikawa
Hiroyuki
H
Kobashi
Motoi
M
Yamada
Yosuke
Y
Kikuchi
Takeshi
T
Mese
Hiroshi
H
Sasaki
Akira
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D031608:Area Postrema / Q000166:cytology*; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007616:Kaolin / Q000008:administration & dosage; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000970:Antineoplastic Agents; D007616:Kaolin; D004399:Dynorphins; D002945:Cisplatin