English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/71073
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

Overexpression of the CHRNA5/A3/B4 genomic cluster in mice increases the sensitivity to nicotine and modifies its reinforcing effects

AuthorsGallego, Xavier; Molas, Susanna; Amador-Arjona, Alejandro; Marks, Michael J.; Robles, Noemí; Murtra, Patricia; Armengol, Lluís; Fernández-Montes, Rubén D.; Gratacòs, Mònica; Pumarola, Martí; Cabrera, Roberto; Maldonado, Rafael; Sabrià, Josefa; Estivill, Xavier; Dierssen, M.
Issue Date2012
PublisherSpringer
CitationAmino Acids 43(2): 897-909 (2012)
AbstractNicotinic acetylcholine receptors (nAChRs) are ligand-gated pentameric ion channels that account for the effects of nicotine. Recent genetic studies have highlighted the importance of variants of the CHRNA5/A3/B4 genomic cluster in human nicotine dependence. Among these genetic variants those found in non-coding segments of the cluster may contribute to the pathophysiology of tobacco use through alterations in the expression of these genes. To discern the in vivo effects of the cluster, we generated a transgenic mouse overexpressing the human CHRNA5/A3/B4 cluster using a bacterial artificial chromosome. Transgenic mice showed increased functional a3b4-nAChRs in brain regions where these subunits are highly expressed under normal physiological conditions. Moreover, they exhibited increased sensitivity to the pharmacological effects of nicotine along with higher activation of the medial habenula and reduced activation of dopaminergic neurons in the ventral tegmental area after acute nicotine administration. Importantly, transgenic mice showed increased acquisition of nicotine self-administration (0.015 mg/kg per infusion) and a differential response in the progressive ratio test. Our study provides the first in vivo evidence of the involvement of the CHRNA5/A3/B4 genomic cluster in nicotine addiction through modifying the activity of brain regions responsible for the balance between the rewarding and the aversive properties of this drug. © Springer-Verlag 2011.
URIhttp://hdl.handle.net/10261/71073
DOI10.1007/s00726-011-1149-y
Identifiersdoi: 10.1007/s00726-011-1149-y
issn: 0939-4451
e-issn: 1438-2199
Appears in Collections:(IN) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.