title: Naloxone-precipitated morphine withdrawal elicits increases in c-fos mRNA expression in restricted regions of the infant rat brain.
abstract: This paper is the first report of a genetic index for morphine withdrawal in infant rats. We examined the effects of naloxone (2 mg/kg) on c-fos mRNA levels in brains of infant and adult rats following repeated treatment with morphine (20 mg/kg, once daily for 5 days). One hour after a single administration of naloxone (naloxone challenge), an increase in c-fos mRNA was observed in the olfactory bulb, hypothalamus and medulla oblongata of infant rats, and in the olfactory bulb and hypothalamus, but not in the medulla oblongata of adult rats. The c-fos mRNA levels returned to control levels 6 h after the naloxone challenge. The increase in c-fos mRNA levels was followed by body weight loss in both infant and adult rats. When MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, was co-administered along with morphine, it inhibited the naloxone-induced increases in c-fos mRNA levels in infant rats following repeated morphine administration. These results suggest that physical dependence develops in infant rats following repeated morphine administration and that the increment of c-fos mRNA levels is a useful indicator for naloxone-precipitated morphine withdrawal in infant as well as in adult rats.
authors.affiliation: Department of Pharmacology, Wakayama Medical University, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Maeda
authors.forename: Shiroh
authors.initials: S
authors.lastname: Kishioka
authors.forename: Norihiro
authors.initials: N
authors.lastname: Inoue
authors.forename: Norifumi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Yohji
authors.initials: Y
authors.lastname: Fukazawa
authors.forename: Masanobu
authors.initials: M
authors.lastname: Ozaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008297:Male; D009021:Morphine Dependence / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D009270:Naloxone