Albertson Dawn N, Schmidt Carl J, Kapatos Gregory, Bannon Michael J
Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Neuropsychopharmacology. 2006 Oct;31(10):2304-12. doi: 10.1038/sj.npp.1301089. Epub 2006 May 3.
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.
药物滥用被认为会因基因表达的改变而导致长期的细胞和行为适应性变化。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Affymetrix微阵列来识别慢性海洛因滥用者死后伏隔核中的基因表达变化。这些数据被独立分析，并与我们之前报道的涉及人类可卡因滥用者的数据相关联，以确定哪些表达变化是药物特异性的，哪些可能是成瘾现象所共有的。在海洛因滥用者中，发现许多编码参与神经递质突触前释放的蛋白质的基因表达显著下降，而在可卡因滥用者队列中未观察到这一发现。相反，在可卡因滥用者中观察到的髓鞘相关基因的显著下降在我们的海洛因受试者队列中并不明显。总体而言，两个药物滥用队列之间在基因表达谱上几乎没有重叠：在大约39000个转录本中，只有25个在可卡因和海洛因滥用者中丰度有显著变化，其中近一半的变化方向相反。这些数据表明，尽管这些药物被认为对该脑区的多巴胺神经传递有共同作用，但与慢性海洛因或可卡因滥用相关的伏隔核基因表达谱在很大程度上是独特的。似乎有必要重新审视我们目前关于与药物滥用相关的分子机制共性的假设。
