Zhang Yong, Liang Yupu, Levran Orna, Randesi Matthew, Yuferov Vadim, Zhao Connie, Kreek Mary Jeanne
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, Box 171, New York, NY, 10065, USA.
Research Bioinformatics, CCTS, The Rockefeller University, New York, NY, 10065, USA.
Psychopharmacology (Berl). 2017 Aug;234(15):2259-2275. doi: 10.1007/s00213-017-4657-y. Epub 2017 Jun 26.
Non-medical use of prescription opioids such as the mu opioid receptor (MOP-r) agonist oxycodone is a growing problem in the USA and elsewhere. There is limited information about oxycodone's impact on diverse gene systems in the brain.
The current study was designed to examine how chronic oxycodone self-administration (SA) affects gene expression in the terminal areas of the nigrostriatal and mesolimbic dopaminergic pathways in mice.
Adult male C57BL/6J mice underwent a 14-day oxycodone self-administration procedure (4 h/day, 0.25 mg/kg/infusion, FR1) and were euthanized 1 h after the last session. The dorsal and ventral striata were dissected, and total RNAs were extracted. Gene expressions were examined using RNA sequencing.
We found that oxycodone self-administration exposure led to alterations of expression in numerous genes related to inflammation/immune functions in the dorsal striatum (54 upregulated genes and 1 downregulated gene) and ventral striatum (126 upregulated genes and 15 downregulated genes), with 38 upregulated genes identified in both brain regions.
This study reveals novel neurobiological mechanisms underlying some of the effects of a commonly abused prescription opioid. We propose that inflammation/immune gene systems may undergo a major change during chronic self-administration of oxycodone.
在美国及其他地区,非医疗用途使用处方阿片类药物,如μ阿片受体(MOP-r)激动剂羟考酮,正成为一个日益严重的问题。关于羟考酮对大脑中多种基因系统的影响,目前的信息有限。
本研究旨在探讨慢性羟考酮自我给药(SA)如何影响小鼠黑质纹状体和中脑边缘多巴胺能通路终末区域的基因表达。
成年雄性C57BL/6J小鼠接受为期14天的羟考酮自我给药程序(每天4小时,0.25毫克/千克/输注,固定比率1),并在最后一次给药后1小时实施安乐死。解剖背侧和腹侧纹状体,提取总RNA。使用RNA测序检测基因表达。
我们发现,羟考酮自我给药暴露导致背侧纹状体(54个上调基因和1个下调基因)和腹侧纹状体(126个上调基因和15个下调基因)中许多与炎症/免疫功能相关的基因表达发生改变,在两个脑区均鉴定出38个上调基因。
本研究揭示了一种常见滥用处方阿片类药物某些作用背后的新神经生物学机制。我们提出,在慢性羟考酮自我给药过程中,炎症/免疫基因系统可能会发生重大变化。