Morphine exposure and abstinence define specific stages of gene expression in the rat nucleus accumbens

被引:60
作者
Spijker, S
Houtzager, SWJ
de Gunst, MCM
de Boer, WPH
Schoffelmeer, ANM
Smit, AB
机构
[1] Free Univ Amsterdam, Dept Mol & Cellular Neurobiol, Grad Sch Neurosci Amsterdam, Neurosci Res Inst, NL-1081 HV Amsterdam, Netherlands
[2] Free Univ Amsterdam, Fac Sci, Dept Math, NL-1081 HV Amsterdam, Netherlands
[3] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, NL-1007 MB Amsterdam, Netherlands
[4] Free Univ Amsterdam, Med Ctr, Dept Med Pharmacol, NL-1081 BT Amsterdam, Netherlands
关键词
real-time quantitative PCR; gene expression profiling; sensitization; addiction; natural withdrawal; bioinformatics;
D O I
10.1096/fj.03-0612fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Intermittent exposure to addictive drugs causes long-lasting changes in responsiveness to these substances due to persistent molecular and cellular alterations within the meso-corticolimbic system. In this report, we studied the expression profiles of 159 genes in the rat nucleus accumbens during morphine exposure (14 days, 10 mg/kg s.c.) and drug-abstinence ( 3 weeks). We used real-time quantitative PCR to monitor gene expression after establishing its sensitivity and resolution to resolve small changes in expression for genes in various abundance classes. Morphine-exposure (5 time points) and subsequent abstinence ( 6 time points) induced phase-specific temporal gene expression of distinct functional groups of genes, for example, short-term homeostatic responses. Opiate withdrawal appeared to be a new stimulus in terms of gene expression and mediates a marked wave of gene repression. Prolonged abstinence resulted in persistently changed expression levels of genes involved in neuronal outgrowth and re-wiring. Our findings substantiate the hypothesis that this new gene program, initiated upon morphine-withdrawal, may subserve long-term neuronal plasticity involved in the persistent behavioral consequences of repeated drug-exposure.
引用
收藏
页码:848 / +
页数:28
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