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rdf:type |
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lifeskim:mentions |
umls-concept:C0004927,
umls-concept:C0007634,
umls-concept:C0023951,
umls-concept:C0026549,
umls-concept:C0027882,
umls-concept:C0040648,
umls-concept:C0205191,
umls-concept:C0332157,
umls-concept:C0547070,
umls-concept:C0599861,
umls-concept:C1280500,
umls-concept:C2825032
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pubmed:issue |
3
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pubmed:dateCreated |
2010-11-2
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pubmed:abstractText |
Repeated exposure to opiates leads to cellular and molecular changes and behavioral alterations reflecting a state of dependence. In noradrenergic neurons, cyclic AMP (cAMP)-dependent pathways are activated during opiate withdrawal, but their contribution to the activity of locus coeruleus noradrenergic neurons and behavioral manifestations remains controversial. Here, we test whether the cAMP-dependent transcription factors cAMP responsive element binding protein (CREB) and cAMP-responsive element modulator (CREM) in noradrenergic neurons control the cellular markers and the physical signs of morphine withdrawal in mice. Using the Cre/loxP system we ablated the Creb1 gene in noradrenergic neurons. To avoid adaptive effects because of compensatory up-regulation of CREM, we crossed the conditional Creb1 mutant mice with a Crem-/- line. We found that the enhanced expression of tyrosine hydroxylase normally observed during withdrawal was attenuated in CREB/CREM mutants. Moreover, the withdrawal-associated cellular hyperactivity and c-fos expression was blunted. In contrast, naloxone-precipitated withdrawal signs, such as jumping, paw tremor, tremor and mastication were preserved. We conclude by a specific genetic approach that the withdrawal-associated hyperexcitability of noradrenergic neurons depends on CREB/CREM activity in these neurons, but does not mediate several behavioral signs of morphine withdrawal.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1471-4159
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pubmed:author |
pubmed-author:Begus-NahrmannYvonneY,
pubmed-author:BuraSimona ASA,
pubmed-author:CruzHansH,
pubmed-author:LüscherChristianC,
pubmed-author:MaldonadoRafaelR,
pubmed-author:MartinMiquelM,
pubmed-author:MurtraPatriciaP,
pubmed-author:OttoChristianeC,
pubmed-author:ParkitnaJan RodriguezJR,
pubmed-author:ParlatoRosannaR,
pubmed-author:SchützGüntherG,
pubmed-author:von Bohlen und HalbachOliverO
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pubmed:copyrightInfo |
© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.
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pubmed:issnType |
Electronic
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pubmed:volume |
115
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
563-73
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pubmed:meshHeading |
pubmed-meshheading:20367754-Animals,
pubmed-meshheading:20367754-Brain,
pubmed-meshheading:20367754-Cell Survival,
pubmed-meshheading:20367754-Chromatography, High Pressure Liquid,
pubmed-meshheading:20367754-Chronic Disease,
pubmed-meshheading:20367754-Cyclic AMP Response Element Modulator,
pubmed-meshheading:20367754-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:20367754-Electrochemistry,
pubmed-meshheading:20367754-Electrophysiology,
pubmed-meshheading:20367754-Female,
pubmed-meshheading:20367754-Genotype,
pubmed-meshheading:20367754-In Situ Hybridization,
pubmed-meshheading:20367754-Locus Coeruleus,
pubmed-meshheading:20367754-Male,
pubmed-meshheading:20367754-Mice,
pubmed-meshheading:20367754-Mice, Knockout,
pubmed-meshheading:20367754-Morphine,
pubmed-meshheading:20367754-Morphine Dependence,
pubmed-meshheading:20367754-Narcotics,
pubmed-meshheading:20367754-Norepinephrine,
pubmed-meshheading:20367754-Substance Withdrawal Syndrome,
pubmed-meshheading:20367754-Sympathetic Nervous System,
pubmed-meshheading:20367754-Transcription Factors
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pubmed:year |
2010
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pubmed:articleTitle |
Effects of the cell type-specific ablation of the cAMP-responsive transcription factor in noradrenergic neurons on locus coeruleus firing and withdrawal behavior after chronic exposure to morphine.
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pubmed:affiliation |
Department of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany. r.parlato@dkfz.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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