Morphine exposure and abstinence define specific stages of gene expression in the rat nucleus accumbens.
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.
Spijker
Sabine
S
Department of Molecular and Cellular Neurobiology, Graduate School Neurosciences Amsterdam, Research Institute Neurosciences,Vrije Universiteit, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands. sspijker@bio.vu.nl
Houtzager
Siard W J
SW
De Gunst
Mathisca C M
MC
De Boer
Wim P H
WP
Schoffelmeer
Anton N M
AN
Smit
August B
AB
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003199:Computer Systems; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000096:biosynthesis / Q000235:genetics; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D018847:Opioid Peptides / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013375:Substance Withdrawal Syndrome / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D018847:Opioid Peptides; D014157:Transcription Factors; D009020:Morphine