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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

J. Neurochem. (2010) 115, 563-573. Abstract 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...

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Main Authors: Parlato, Rosanna (Author) , Cruz, Hans (Author) , Otto, Christiane (Author) , Murtra, Patricia (Author) , Rodriguez-Parkitna, Jan (Author) , Martin, Miquel (Author) , Bura, Simona A. (Author) , Begus-Nahrmann, Yvonne (Author) , Von Bohlen und Halbach, Oliver (Author) , Maldonado, Rafael (Author) , Schütz, Günther (Author) , Lüscher, Christian (Author)
Format: Article (Journal)
Language:English
Published: 29 March 2010
In: Journal of neurochemistry
Year: 2010, Volume: 115, Issue: 3, Pages: 563-573
ISSN:1471-4159
DOI:10.1111/j.1471-4159.2010.06709.x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/j.1471-4159.2010.06709.x
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1471-4159.2010.06709.x
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Author Notes:Rosanna Parlato, Hans Cruz, Christiane Otto, Patricia Murtra, Jan Rodriguez Parkitna, Miquel Martin, Simona A. Bura, Yvonne Begus-Nahrmann, Oliver Von Bohlen und Halbach, Rafael Maldonado, Günther Schütz and Christian Lüscher
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Summary:J. Neurochem. (2010) 115, 563-573. Abstract 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.
Item Description:Gesehen am 26.06.2023
Physical Description:Online Resource
ISSN:1471-4159
DOI:10.1111/j.1471-4159.2010.06709.x

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