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Protracted abstinence from distinct drugs of abuse shows regulation of a common gene network

机译:对不同滥用药物的长期禁令显示出对共同基因网络的调节

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Addiction is a chronic brain disorder. Prolonged abstinence from drugs of abuse involves dysphoria, high stress responsiveness and craving. The neurobiology of drug abstinence, however, is poorly understood. We previously identified a unique set of hundred mu-opioid receptor-dependent genes in the extended amygdala, a key site for hedonic and stress processing in the brain. Here we examined these candidate genes either immediately after chronic morphine, nicotine, ?9-tetrahydrocannabinol or alcohol, or following 4 weeks of abstinence. Regulation patterns strongly differed among chronic groups. In contrast, gene regulations strikingly converged in the abstinent groups and revealed unforeseen common adaptations within a novel huntingtin-centered molecular network previously unreported in addiction research. This study demonstrates that, regardless the drug, a specific set of transcriptional regulations develops in the abstinent brain, which possibly contributes to the negative affect characterizing protracted abstinence. This transcriptional signature may represent a hallmark of drug abstinence and a unitary adaptive molecular mechanism in substance abuse disorders.
机译:成瘾是一种慢性脑疾病。长期禁忌滥用药物会导致烦躁不安,高压力反应和渴望。然而,戒毒的神经生物学知之甚少。我们先前在延伸的杏仁核中确定了一组独特的数百个μ阿片受体依赖性基因,杏仁核是大脑享乐和压力处理的关键部位。在这里,我们在慢性吗啡,尼古丁,α9-四氢大麻酚或酒精后或戒酒4周后立即检查了这些候选基因。慢性人群之间的调节模式差异很大。相比之下,基因调节则惊人地集中在戒酒的人群中,并揭示了在成瘾研究中未曾报道过的新型以亨廷顿为中心的分子网络中不可预见的常见适应。这项研究表明,不管使用哪种药物,禁欲脑中都会出现一组特定的转录调控,这可能会导致长期禁欲的负面影响。该转录签名可能代表药物滥用障碍中禁毒和统一的适应性分子机制的标志。

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