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Butorphanol dependence increases hippocampal κ‐opioid receptor gene expression
Author(s) -
Tanaka Sachiko,
Fan LirWan,
Tien LuTai,
Park Younjoo,
LiuChen LeeYuan,
Rockhold Robin William,
Ho Ing Kang
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20620
Subject(s) - butorphanol , hippocampal formation , opioid , receptor , opioid receptor , neuroscience , gene , pharmacology , psychology , biology , genetics
Abstract Butorphanol is a synthetic opioid agonist/antagonist analgesic agent, which exerts its effects mainly via κ‐opioid receptors. Characterizations of the gene expression levels of the mRNA for and protein levels of the κ‐opioid receptor in different brain regions of rats are essential for investigating possible mechanisms in the development of physical dependence on and withdrawal from butorphanol. Animals were rendered dependent by intracerebroventricular (i.c.v.) infusion of butorphanol (26 nmol/μl/hr) via osmotic minipumps for 3 days. Rats were sacrificed immediately (dependent group) or 7 hr after discontinuation of i.c.v. butorphanol infusion (withdrawal group). Expression levels of the mRNA for the κ‐opioid receptor, as detected by reverse transcription‐polymerase chain reaction followed by Southern blot analysis, were significantly increased in the cerebral cortex, striatum, and midbrain, including thalamus, hippocampus, and pons, in animals dependent on butorphanol. In both dependent and withdrawal groups, Western blot analysis of κ‐opioid receptor protein levels showed significant increases in the amygdaloid nucleus, paraventricular thalamus, and thalamus. However, in the withdrawal group, there were significant decreases in the hippocampus and cortical regions, including the frontal, parietal, and temporal cortex. Regional changes in the mRNA for and protein levels of the κ‐opioid receptor focus attention on highly special roles for this receptor in the development of physical dependence on and the expression of withdrawal from butorphanol dependence. © 2005 Wiley‐Liss, Inc.