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Morphine exposure and abstinence define specific stages of gene expression in the rat nucleus accumbens
Author(s) -
Spijker Sabine,
Houtzager Siard W. J.,
Gunst Mathisca C. M.,
Boer Wim P. H.,
Schoffelmeer Anton N. M.,
Smit August B.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0612fje
Subject(s) - nucleus accumbens , abstinence , gene expression , morphine , immediate early gene , addiction , gene , opiate , neuroscience , biology , psychology , pharmacology , genetics , central nervous system , psychiatry , receptor
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.