Escalated Oxycodone Self-Administration Causes Differential Striatal mRNA Expression of FGFs and IEGs Following Abstinence-Associated Incubation of Oxycodone Craving
Escalated Oxycodone Self-Administration Causes Differential Striatal mRNA Expression of FGFs and IEGs Following Abstinence-Associated Incubation of Oxycodone Craving
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DOI：
10.1016/j.neuroscience.2019.07.030
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发表时间：
2019-09-01
期刊：
影响因子：
3.3
通讯作者：
Cadet, Jean Lud
中科院分区：
文献类型：
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作者：
Blackwood, Christopher A.;Leary, Michael;Cadet, Jean Lud
对包括羟考酮在内的处方阿片类药物的成瘾已经达到了悲惨的程度。在此，我们研究了成纤维细胞生长因子（FGF）和即刻早期基因（IEG）与羟考酮自我给药（SA）增加后戒断诱导的药物渴求孵化的相关性。训练大鼠自我施用羟考酮4周。在停药1个月期间，在不同的时间间隔进行寻找试验。在最后一次测试后1天对大鼠实施安乐死，并解剖延髓核和背侧纹状体用于PCR分析。给予长时间（LgA，9 h）而非短时间（ShA，3 h）药物给药的大鼠增加了其羟考酮摄入量，并在戒断期间表现出羟考酮寻求的潜伏期。这些大鼠背侧纹状体中fgf 2的表达呈剂量依赖性增加。Fgfr 2的表达在LgA组纹状体中也显著增加，但ShA组没有。同样，纹状体c-fos和junB mRNA水平在LGA大鼠中表现出更大的增加。观察到FGF mRNA水平在背侧纹状体比在LGA大鼠的NAc中改变更多，这表明纹状体FGF表达的变化可能比NAc中的改变对羟考酮渴望的孵育更显著。靶向FGF信号通路可能为阿片类药物成瘾提供新的策略。(C)2019年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Addiction to prescribed opioids including oxycodone has reached tragic levels. Herein, we investigated the relevance of fibroblast growth factors (FGFs) and immediate early genes (IEGs) to withdrawal-induced incubation of drug craving following escalated oxycodone self-administration (SA). Rats were trained to self-administer oxycodone for 4 weeks. Seeking tests were performed at various intervals during 1 month of drug withdrawal. Rats were euthanized 1 day after the last test and nucleus accumbens and dorsal striata were dissected for use in PCR analyses. Rats given long access (LgA, 9 h), but not short access (ShA, 3 h) to drug escalated their oxycodone intake and exhibited incubation of oxycodone seeking during withdrawal. These rats exhibited dose-dependent increases in fgf2 expression in the dorsal striatum. Fgfr2 expression was also significantly increased in the striatum in LgA, but not ShA groups. Similarly, striatal c-fos and junB mRNA levels showed greater increases in LgA rats. The observations that fgf mRNA levels were more altered in the dorsal striatum than in the NAc of LgA rats suggest that changes in striatal FGF expression may be more salient to incubation of oxycodone craving than alterations in the NAc. Targeting FGF signaling pathways might offer novel strategies against opioid addiction. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.