The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by male adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions/day for 5 consecutive days/week for 3 weeks. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 – 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in biological processes involved with cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce changes in neuronal function.
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机译：这项研究的目的是确定雄性青醇（P）大鼠暴饮暴食后酒后延伸杏仁核内基因表达的变化。从28日龄开始，每天给P大鼠同时提供15和30％乙醇，连续3天，每周3次，每天1次，连续3天。饮酒第15天的第一次乙醇接触后3小时，以斩首法杀死大鼠。从伏核壳（Acb-sh）和杏仁核中央核（CeA）的微穿孔样品中制备RNA。乙醇摄入量为2.5 – 3.0 g / kg /疗程。在Acb-sh和CeA中，水和乙醇组之间分别有154个和182个独特命名的基因，它们之间存在显着差异（FDR = 0.2）。基因本体论（GO）分析表明，青春期暴饮暴食在涉及Acb-sh中细胞增殖和细胞结构调控以及CeA中神经元投射和细胞组织正调控的生物学过程中产生了变化。独创性途径分析表明，在Acb-sh中，青少年饮酒会改变几种主要的细胞内信号传导途径（例如cAMP介导的蛋白激酶A信号传导途径），而上调的基因比下调的基因多3倍在酒精组中。酒精基团的CeA中cAMP介导的信号系统也被上调。加权基因共表达网络分析表明，Acb-sh和CeA分别具有明显的G蛋白偶联受体信号传导和跨膜受体蛋白激酶信号传导类别。总体而言，这项研究的结果表明，青春期P大鼠饮酒般的酗酒正在差异地改变Acb-sh和CeA中的基因表达，其中一些基因参与细胞内信号传导途径，并可能导致神经元功能的改变。
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