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

• Published in: Neuroscience letters Vol. 424; no. 2; pp. 122 - 126
• Main Authors: Tsukamoto, Goichi, Ichikawa, Hiroyuki, Kobashi, Motoi, Yamada, Yosuke, Kikuchi, Takeshi, Mese, Hiroshi, Sasaki, Akira
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 07-09-2007; Elsevier
• Subjects: Animals; Anorexia; Antineoplastic Agents - pharmacology; Area Postrema - cytology; Behavior, Animal - drug effects; Biological and medical sciences; Cell Count; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cisplatin; Cisplatin - pharmacology; Delayed emesis; Dose-Response Relationship, Drug; Dynorphin; Dynorphins - metabolism; Eating - drug effects; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Immunohistochemistry; Kaolin - administration & dosage; Male; Neurons - cytology; Neurons - drug effects; Pica; Rats; Rats, Sprague-Dawley; Time Factors; Vertebrates: nervous system and sense organs; Immunohistochemistry; Anorexia; Pica; Cisplatin; Delayed emesis; Dynorphin; Ependymal organ; Rat; Rodentia; Central nervous system; Neuropeptide; Opioid peptide; Long term; Encephalon; Vertebrata; Mammalia; Area postrema; Neuron; Animal
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2007.07.044

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 10
mg/kg body weight cisplatin (i.p.) and their behavior was monitored for 72
h. We observed a delayed increase in pica 24
-72
h after injection, compared to the 24
h 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 10
mg/kg cisplatin led to an increase in kaolin intake on day 1. Administration of 5 and 10
mg/kg of cisplatin led to decreased intake of laboratory chow (MF) on days 1–3, but 10
mg/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 72
h post-administration of 1 and 5
mg/kg cisplatin. Administration of 5
mg/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 72
h 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.