Overexpression of 伪3/伪5/尾4 nicotinic receptor subunits modifies impulsive-like behavior

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• 作者：Xavier Viñ ; als^a ; Susanna Molas^b ; Xavier Gallego^b ; Rubé ; n D. Ferná ; ndez-Montes^b ; Patricia Robledo^a ; ^c ; Mara Dierssen^b ; Rafael Maldonado^a ; ^{rafael.maldonado@upf.edu}
• 关键词：Nicotine dependence ; Gene variants ; CHRNA3/A5/B4 gene cluster ; Nicotine acetylcholine receptor ; Delayed alternation
• 刊名：Drug and Alcohol Dependence
• 出版年：2012
• 期刊代码：81_03768716
• 类别：med
• 出版时间：1 May, 2012
• 卷：122
• 期：3
• 页码：247-252
• 文件大小：603 K

摘要

Recent studies have revealed that sequence variants in genes encoding the 伪3/伪5/尾4 nicotinic acetylcholine receptor subunits are associated with nicotine dependence. In this study, we evaluated two specific aspects of executive functioning related to drug addiction (impulsivity and working memory) in transgenic mice over expressing 伪3/伪5/尾4 nicotinic receptor subunits. Impulsivity and working memory were evaluated in an operant delayed alternation task, where mice must inhibit responding between 2 and 8 s in order to receive food reinforcement. Working memory was also evaluated in a spontaneous alternation task in an open field. Transgenic mice showed less impulsive-like behavior than wild-type controls, and this behavioral phenotype was related to the number of copies of the transgene. Thus, transgenic Line 22 (16-28 copies) showed a more pronounced phenotype than Line 30 (4-5 copies). Overexpression of these subunits in Line 22 reduced spontaneous alternation behavior suggesting deficits in working memory processing in this particular paradigm. These results reveal the involvement of 伪3/伪5/尾4 nicotinic receptor subunits in working memory and impulsivity, two behavioral traits directly related to the vulnerability to develop nicotine dependence.