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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| Hauptverfasser: | , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
29 March 2010
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| In: |
Journal of neurochemistry
Year: 2010, Jahrgang: 115, Heft: 3, Pages: 563-573 |
| ISSN: | 1471-4159 |
| DOI: | 10.1111/j.1471-4159.2010.06709.x |
| Online-Zugang: | 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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| Verfasserangaben: | 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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| 245 | 1 | 0 | |a 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 |c 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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| 520 | |a 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. | ||
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