Gene profiling the response to repeated cocaine self-administration in dorsal striatum: A focus on circadian genes
Gene profiling the response to repeated cocaine self-administration in dorsal striatum: A focus on circadian genes
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DOI：
10.1016/j.brainres.2008.02.106
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发表时间：
2008-06-05
期刊：
影响因子：
2.9
通讯作者：
Taylor, Jane R.
中科院分区：
文献类型：
--
作者：
Lynch, Wendy J.;Girgenti, Matthew J.;Taylor, Jane R.
慢性可卡因暴露引起的背纹状体基因表达的改变与可卡因成瘾相关的长期行为改变有关。为了进一步了解由于可卡因自我给药而发生的分子改变，我们对基因表达进行了微阵列分析，然后进行了生物信息学基因网络分析，使我们能够确定基因表达水平上的适应以及相互连接的网络。在24小时的离散试验模式下（平均98 mg/kg/天），在自我给药7天后，观察大鼠背纹状体基因表达的变化。在这里，我们报告了昼夜节律基因Clock， Bmal1, Cryptochrome1， Period2以及一些受昼夜节律系统（即早期生长反应1，dynorphin）调节/相关的基因的调控。我们还观察到其他相关基因（即Nur77， β - catenin）的调控。然后将这些变化与确定受可卡因自我服用影响的昼夜节律过程的精心策划的途径和制定的网络联系起来。这些数据有力地表明，与昼夜节律相关的基因参与了大脑对可卡因的反应，并可能有助于理解成瘾行为，包括睡眠中断和昼夜节律。Elsevier B.V.出版
Alterations in gene expression in the dorsal striatum caused by chronic cocaine exposure have been implicated in the long-term behavioral changes associated with cocaine addiction. To gain further insight into the molecular alterations that occur as a result of cocaine self-administration, we conducted a microarray analysis of gene expression followed by bioinformatic gene network analysis that allowed us to identify adaptations at the level of gene expression as well as into interconnected networks. Changes in gene expression were examined in the dorsal striatum of rats 1 day after they had self-administered cocaine for 7 days under a 24-h access, discrete trial paradigm (averaging 98 mg/kg/day). Here we report the regulation of the circadian genes Clock, Bmal1, Cryptochrome1, Period2, as well as several genes that are regulated by/associated with the circadian system (i.e., early growth response 1, dynorphin). We also observed regulation of other relevant genes (i.e., Nur77, beta catenin). These changes were then linked to curated pathways and formulated networks which identified circadian rhythm processes as affected by cocaine self-administration. These data strongly suggest involvement of circadian-associated genes in the brain's response to cocaine and may contribute to an understanding of addictive behavior including disruptions in sleep and circadian rhythmicity. Published by Elsevier B.V.