Gene expression changes in the medial prefrontal cortex and nucleus accumbens following abstinence from cocaine self-administration.

Gene expression changes in the medial prefrontal cortex and nucleus accumbens following abstinence from cocaine self-administration.
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DOI:
10.1186/1471-2202-11-29
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发表时间:
2010-02-26
期刊:
影响因子:
2.4
通讯作者:
Vrana KE
Vrana KE
中科院分区:
医学4区
文献类型:
--
作者:
Freeman WM;Lull ME;Patel KM;Brucklacher RM;Morgan D;Roberts DC;Vrana KE

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许多可卡因反应基因表达的研究都集中在可卡因暴露过程中发生的变化,但很少有研究探讨这些变化与可卡因戒断的持久性。基因表达的持续变化以及戒断过程中诱导的改变可能是长期药物渴望和复发倾向的基础。全基因组表达分析进行了大鼠可卡因狂欢戒断模型,以前已被证明会产生增加的药物寻求和服用与禁欲。两个中脑边缘终末区域(mPFC和NAc)的基因表达变化在可卡因未处理大鼠与可卡因自我给药10天后,随后强制戒断1、10或100天的大鼠(每组n = 6-11)的比较中得到鉴定。mPFC中共有1,461个基因和NAc中共有414个基因在至少两个时间点之间发生了改变(ANOVA,p < 0.05; ± 1.4倍变化)。这些基因可以细分为:1)可卡因自我给药的变化,这些变化不会持续到戒断期,2)可卡因自我给药的变化,这些变化会持续到戒断期,3)可卡因自我给药没有变化,但在强制戒断期间发生了变化。进行qPCR分析以确认在微阵列分析中观察到的基因表达变化。总之,这些变化有助于阐明参与禁欲诱导行为的过程和网络,包括突触可塑性,MAPK信号传导和TNF信号传导。
Many studies of cocaine-responsive gene expression have focused on changes occurring during cocaine exposure, but few studies have examined the persistence of these changes with cocaine abstinence. Persistent changes in gene expression, as well as alterations induced during abstinence may underlie long-lasting drug craving and relapse liability. Whole-genome expression analysis was conducted on a rat cocaine binge-abstinence model that has previously been demonstrated to engender increased drug seeking and taking with abstinence. Gene expression changes in two mesolimbic terminal fields (mPFC and NAc) were identified in a comparison of cocaine-naïve rats with rats after 10 days of cocaine self-administration followed by 1, 10, or 100 days of enforced abstinence (n = 6-11 per group). A total of 1,461 genes in the mPFC and 414 genes in the NAc were altered between at least two time points (ANOVA, p < 0.05; ± 1.4 fold-change). These genes can be subdivided into: 1) changes with cocaine self-administration that do not persist into periods of abstinence, 2) changes with cocaine self-administration that persist with abstinence, 3) and those not changed with cocaine self-administration, but changed during enforced abstinence. qPCR analysis was conducted to confirm gene expression changes observed in the microarray analysis. Together, these changes help to illuminate processes and networks involved in abstinence-induced behaviors, including synaptic plasticity, MAPK signaling, and TNF signaling.
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发表时间: 2008-06-13
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