Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse
Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse
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DOI：
10.1038/sj.npp.1301089
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发表时间：
2006-10-01
影响因子：
7.6
通讯作者：
Bannon, Michael J.
中科院分区：
文献类型：
--
作者：
Albertson, Dawn N.;Schmidt, Carl J.;Bannon, Michael J.
药物滥用被认为是由于基因表达的改变而引起长期的细胞和行为适应。了解成瘾的分子后果可能有助于开发更好的治疗策略。本研究利用高通量的Affytron微阵列，以确定慢性海洛因滥用者死后的丘脑核基因表达的变化。这些数据进行了独立的分析，并与我们以前报道的涉及人类可卡因滥用者的数据，以确定哪些表达变化是药物特异性的，哪些可能是常见的成瘾现象。在海洛因滥用者中，许多编码神经递质突触前释放蛋白质的基因表达显著减少，这一发现在可卡因滥用队列中没有发现。相反，在可卡因滥用者中观察到的髓鞘相关基因的显著减少在我们的海洛因受试者队列中并不明显。总体而言，在两个药物滥用队列之间的基因表达谱几乎没有重叠：在调查的大约39000个转录本中，可卡因和海洛因滥用者中只有25个转录本的丰度发生了显着变化，其中近一半的转录本在相反的方向上发生了变化。这些数据表明，与慢性海洛因或可卡因滥用相关的神经核基因表达谱在很大程度上是独特的，尽管这些药物被认为对该大脑区域的多巴胺神经传递有共同的影响。重新审视我们目前关于物质滥用相关分子机制共性的假设似乎是有必要的。
Drug abuse is thought to induce long-term cellular and behavioral adaptations as a result of alterations in gene expression. Understanding the molecular consequences of addiction may contribute to the development of better treatment strategies. This study utilized high-throughput Affymetrix microarrays to identify gene expression changes in the post-mortem nucleus accumbens of chronic heroin abusers. These data were analyzed independently and in relation to our previously reported data involving human cocaine abusers, in order to determine which expression changes were drug specific and which may be common to the phenomenon of addiction. A significant decrease in the expression of numerous genes encoding proteins involved in presynaptic release of neurotransmitter was seen in heroin abusers, a finding not seen in the cocaine-abusing cohort. Conversely, the striking decrease in myelin-related genes observed in cocaine abusers was not evident in our cohort of heroin subjects. Overall, little overlap in gene expression profiles was seen between the two drug-abusing cohorts: out of the approximately 39 000 transcripts investigated, the abundance of only 25 was significantly changed in both cocaine and heroin abusers, with nearly one-half of these being altered in opposite directions. These data suggest that the profiles of nucleus accumbens gene expression associated with chronic heroin or cocaine abuse are largely unique, despite what are thought to be common effects of these drugs on dopamine neurotransmission in this brain region. A re-examination of our current assumptions about the commonality of molecular mechanisms associated with substance abuse seems warranted.