The endogenous opioid system in human alcoholics: molecular adaptations in brain areas involved in cognitive control of addiction
The endogenous opioid system in human alcoholics: molecular adaptations in brain areas involved in cognitive control of addiction
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DOI：
10.1111/j.1369-1600.2011.00366.x
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发表时间：
2013-01-01
影响因子：
3.4
通讯作者：
Bakalkin, Georgy
中科院分区：
文献类型：
--
作者：
Bazov, Igor;Kononenko, Olga;Bakalkin, Georgy
内源性阿片系统（EOS）在成瘾过程中起着关键作用。该系统中的分子失调可能对成瘾周期的不同阶段和所涉及的神经回路具有特异性，因此可能对成瘾的启动和维持有不同的贡献。在这里，我们评估是否EOS是改变的大脑区域参与认知控制成瘾，包括背外侧前额叶皮层（dl-PFC），眶额皮层（OFC）和海马在人类酒精依赖的主题。EOS mRNA水平的定量逆转录-聚合酶链反应（qRT-PCR）和强啡肽水平的放射免疫测定法（RIA）从14个酗酒者和14个对照组获得的尸检标本进行了测量。dl-PFC中强啡肽原mRNA和强啡肽酗酒者OFC阿片受体mRNA和海马强啡肽表达上调。前脑啡肽原和μ-和d-阿片受体的表达无显著变化;前阿黑皮素mRNA水平低于检测限。激活？-强啡肽上调对阿片受体的影响可能是成瘾相关的神经认知功能障碍和抑制控制中断的部分基础。
The endogenous opioid system (EOS) plays a critical role in addictive processes. Molecular dysregulations in this system may be specific for different stages of addiction cycle and neurocircuitries involved and therefore may differentially contribute to the initiation and maintenance of addiction. Here we evaluated whether the EOS is altered in brain areas involved in cognitive control of addiction including the dorsolateral prefrontal cortex (dl-PFC), orbitofrontal cortex (OFC) and hippocampus in human alcohol-dependent subjects. Levels of EOS mRNAs were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and levels of dynorphins by radioimmunoassay (RIA) in post-mortem specimens obtained from 14 alcoholics and 14 controls. Prodynorphin mRNA and dynorphins in dl-PFC, ?-opioid receptor mRNA in OFC and dynorphins in hippocampus were up-regulated in alcoholics. No significant changes in expression of proenkephalin, and mu- and d-opioid receptors were evident; pro-opiomelanocortin mRNA levels were below the detection limit. Activation of the ?-opioid receptor by up-regulated dynorphins in alcoholics may underlie in part neurocognitive dysfunctions relevant for addiction and disrupted inhibitory control.