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  Orexin-Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine

Navarro, G., Quiroz, C., Moreno-Delgado, D., Sierakowiak, A., McDowell, K., Moreno, E., et al. (2015). Orexin-Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine. JOURNAL OF NEUROSCIENCE, 35(17), 6639-6653. doi:10.1523/JNEUROSCI.4364-14.2015.

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Datensatz-Permalink: https://hdl.handle.net/11858/00-001M-0000-0028-8CAE-C Versions-Permalink: https://hdl.handle.net/11858/00-001M-0000-0028-8CAF-A
Genre: Zeitschriftenartikel

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Urheber

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 Urheber:
Navarro, Gemma1, Autor
Quiroz, Cesar1, Autor
Moreno-Delgado, David1, Autor
Sierakowiak, Adam1, Autor
McDowell, Kimberly1, Autor
Moreno, Estefania1, Autor
Rea, William1, Autor
Cai, Ning-Sheng1, Autor
Aguinaga, David1, Autor
Howell, Lesley A.1, Autor
Hausch, Felix2, Autor           
Cortes, Antonio1, Autor
Mallol, Josefa1, Autor
Casado, Vicent1, Autor
Lluis, Carme1, Autor
Canela, Enric I.1, Autor
Ferre, Sergi1, Autor
McCormick, Peter J.1, Autor
Affiliations:
1external, ou_persistent22              
2Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              

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 Zusammenfassung: Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target sigma(1) receptor (sigma R-1) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the sigma R-1-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking.

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Sprache(n): eng - English
 Datum: 2015-04-29
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000353647600003
DOI: 10.1523/JNEUROSCI.4364-14.2015
 Art des Abschluß: -

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Titel: JOURNAL OF NEUROSCIENCE
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: Washington DC, USA : Society for Neuroscience
Seiten: - Band / Heft: 35 (17) Artikelnummer: - Start- / Endseite: 6639 - 6653 Identifikator: ISSN: 0270-6474