Protection Genes in Nucleus Accumbens Shell Affect Vulnerability to Nicotine Self-Administration across Isogenic Strains of Adolescent Rat
Protection Genes in Nucleus Accumbens Shell Affect Vulnerability to Nicotine Self-Administration across Isogenic Strains of Adolescent Rat
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DOI：
10.1371/journal.pone.0086214
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发表时间：
2014-01-22
期刊：
影响因子：
3.7
通讯作者：
Sharp, Burt M.
中科院分区：
文献类型：
--
作者：
Chen, Hao;Luo, Rui;Sharp, Burt M.
经典的遗传学研究表明，吸烟的遗传率为0.4 - 0.6，多个基因赋予吸烟的易感性和抵抗力。尽管最近在识别与吸烟行为相关的基因方面取得了进展，但这种遗传性的主要来源及其对易感性和抵抗力的影响在很大程度上是未知的。静脉内尼古丁的操作性自我给药（SA）是吸烟行为的既定模型。我们最近证实，遗传因素对同基因大鼠品系的尼古丁摄入量有很强的控制作用。由于传入多巴胺能信号的处理核壳（AcbS）是至关重要的收购和维护的动机行为加强尼古丁，我们假设，差异基础基因表达AcbS占大部分的应变应变变化尼古丁SA。因此，我们对通过激光捕获显微切割从10个同基因青春期大鼠品系获得的AcbS样品的转录组进行测序，并比较所有RNA转录水平与行为。加权基因共表达网络分析，一种系统生物学方法，发现了12个模块（即，在所有样本中协变的独特基因组）相关（p
Classical genetic studies show the heritability of cigarette smoking is 0.4-0.6, and that multiple genes confer susceptibility and resistance to smoking. Despite recent advances in identifying genes associated with smoking behaviors, the major source of this heritability and its impact on susceptibility and resistance are largely unknown. Operant self-administration (SA) of intravenous nicotine is an established model for smoking behavior. We recently confirmed that genetic factors exert strong control over nicotine intake in isogenic rat strains. Because the processing of afferent dopaminergic signals by nucleus accumbens shell (AcbS) is critical for acquisition and maintenance of motivated behaviors reinforced by nicotine, we hypothesized that differential basal gene expression in AcbS accounts for much of the strain-to-strain variation in nicotine SA. We therefore sequenced the transcriptome of AcbS samples obtained by laser capture microdissection from 10 isogenic adolescent rat strains and compared all RNA transcript levels with behavior. Weighted gene co-expression network analysis, a systems biology method, found 12 modules (i.e., unique sets of genes that covary across all samples) that correlated (p