Heroin self-administration: II. CNS gene expression following withdrawal and cue-induced drug-seeking behavior
Heroin self-administration: II. CNS gene expression following withdrawal and cue-induced drug-seeking behavior
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DOI：
10.1016/j.pbb.2008.03.019
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发表时间：
2008-09-01
影响因子：
3.6
通讯作者：
Vrana, Kent E.
中科院分区：
文献类型：
--
作者：
Kuntz, Kara L.;Patel, Kruti M.;Vrana, Kent E.
在随附的论文中，我们描述了在戒断14天后大鼠的海洛因寻求行为的潜伏期。为了了解伴随这种行为观察的基因组变化，我们测量了先前报道的对药物滥用有反应的基因的表达。具体来说，1或14天的禁欲后，mRNA表达的内侧前额叶皮层（mPFC）和核延髓（NAc）后立即测量一个单一的90分钟的灭绝会话的11个基因。此外，在对照组大鼠中检查了应急的作用，对照组大鼠接受了非反应依赖性海洛因给药。通过实时定量PCR定量基因表达。mPFC中五个基因（Arc、EGR 1、EGR 2、Fos和Homer 1b/c）的表达发生了变化。EGR 1和EGR 2的表达增加后，90分钟的灭绝会议在一个应急特定的水手，这种增加持续通过14天的禁欲。在禁欲1天和14天后，Fos表达也增加，但在14天，这种增加是反应无关的（即，它发生在有海洛因自我给药史的大鼠和对照组中）。弧表达增加后灭绝会议只在大鼠海洛因自我管理的历史，只有当测试后1，但不是14天的禁欲。Homer 1 B/c下降后，14天的强制禁欲大鼠接受非特遣队海洛因。NAc中仅单个基因（EGR 2）的表达增加。这些数据表明，行为孵化与特定转录物水平的改变一致，并且这种反应是偶然特异性的。此外，EGR 1和EGR 2在灭绝后的自我管理大鼠中特异性上调，并且这一发现持续到14天的禁欲，表明这些基因特别与孵化现象相关。这些观察到的持续变化，在基因表达后禁欲可能反映复发的易感性的分子相关性。(C)2008年爱思唯尔公司All rights reserved.
In the accompanying paper, we described incubation of heroin-seeking behavior in rats following 14 days of abstinence. To gain an understanding of genomic changes that accompany this behavioral observation, we measured the expression of genes previously reported to respond to drugs of abuse. Specifically, after 1 or 14 days of abstinence, m RNA expression was measured for 11 genes in the medial prefrontal cortex (mPFC)and nucleus accumbens (NAc) immediately following a single 90 min extinction session. Additionally, the role of contingency was examined in control rats that received yoked, response-independent heroin administration. Gene expression was quantified by real-time quantitative PCR. Expression of five genes (Arc, EGR1, EGR2, Fos, and Homer1b/c) was changed in the mPFC. EGR1 and EGR2 expression was increased following the 90 min extinction session in a contingency-specific mariner and this increase persisted through the 14 days of abstinence. Fos expression was also increased after 1 and 14 days of abstinence, but at 14 days this increase was response-independent (i.e., it occurred in both the rats with a history of heroin self-administration and in the yoked controls). Arc expression increased following the extinction session only in rats with a history of heroin self-administration and only when tested following 1, but not 14, days of abstinence. Homer 1 b/c decreased after 14 days of enforced abstinence in rats that received non-contingent heroin. Expression of only a single gene (EGR2) was increased in the NAc. These data demonstrate that behavioral incubation is coincident with altered levels of specific transcripts and that this response is contingently-specific. Moreover, EGR1 and EGR2 are specifically upregulated in self-administering rats following extinction and this finding persists through 14 days of abstinence, suggesting that these genes are particularly associated with the incubation phenomenon. These latter observations of persistent changes in gene expression following abstinence may reflect molecular correlates of relapse liability. (C) 2008 Elsevier Inc. All rights reserved.