Precipitated morphine withdrawal stimulates multiple activator protein-1 signaling pathways in rat brain.
Morphine dependence is a long lasting form of neuronal plasticity. Naloxone-precipitated morphine withdrawal, a model of opioid dependence, induces brain region-specific changes in activator protein-1 (AP-1) transcription factor gene expression. Rapid increases in c-fos, fos-B, jun-B, and c-jun mRNA levels accompany withdrawal, with the relative level of induction correlating with the severity of physical dependence. Altered patterns of c-fos mRNA expression were limited to neuronal circuits mediating stress responses, motivation, and cognition. AP-1 DNA-binding activity and dimer composition also exhibited regulation after withdrawal, presumably as a result of both transcriptional and post-translational events. Thus, morphine dependence results in the alteration of diverse, brain region-specific, signal transcription pathways involving AP-1 transcription factors.
Vollum Institute, Oregon Health Sciences University, Portland 97201.
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Couceyro
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Douglass
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016762:Genes, fos; D016758:Genes, jun; D017403:In Situ Hybridization; D008297:Male; D009020:Morphine / Q000633:toxicity*; D009270:Naloxone / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000503:physiopathology*; D019966:Substance-Related Disorders / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000494:pharmacology*
D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D009270:Naloxone; D009020:Morphine; D004247:DNA