Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA.
BMC Neurosci. 2010 Feb 26;11:29. doi: 10.1186/1471-2202-11-29.
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.
许多可卡因反应基因表达的研究都集中在可卡因暴露期间发生的变化上，但很少有研究检查这些变化在可卡因戒断后的持续情况。基因表达的持续变化，以及戒断期间诱导的改变，可能是长期药物渴望和复发倾向的基础。
对以前已经证明会导致戒断时增加药物寻求和摄取的大鼠可卡因 binge-abstinence 模型进行了全基因组表达分析。通过比较可卡因-naïve 大鼠与可卡因自我给药 10 天后、再强制戒断 1、10 或 100 天的大鼠，鉴定了两个中脑边缘终末场（mPFC 和 NAc）中的基因表达变化（每组 n = 6-11）。mPFC 中有 1461 个基因和 NAc 中有 414 个基因在至少两个时间点发生了改变（ANOVA，p < 0.05； +/- 1.4 倍变化）。这些基因可以分为：1）可卡因自我给药引起的变化，但不会持续到戒断期，2）可卡因自我给药引起的变化，但在戒断期持续，3）没有可卡因自我给药引起的变化，但在强制戒断期间发生变化。qPCR 分析用于确认微阵列分析中观察到的基因表达变化。
这些变化共同阐明了与戒断诱导行为相关的过程和网络，包括突触可塑性、MAPK 信号和 TNF 信号。
