GENES REGULATED BY ABUSED DRUGS

滥用药物会通过生化机制对行为产生长期的改变，而这些机制在很大程度上是未知的。药物改变了大脑中特定基因表达的变化，可以为成瘾的可能生化基础提供一个主要窗口。为了进一步探索这一领域，我们现在越来越多地关注阵列杂交技术，该技术已经允许鉴定数十种不同的cdna，这些cdna对应于大脑中表达的候选药物调节基因。在这一年中，我们加强了候选基因的表征，这些基因的表达受安非他明、可卡因和吗啡的调节。我们可以将这些数据与缺乏单个或多个受体和转运体基因的敲除小鼠的结果进行比较。利用微阵列技术，我们已经能够从大约38%的寡核苷酸DNA微阵列基因中检测到可重复的阳性杂交信号，并鉴定出大约1-2%的基因通过敲除或药物可重复调节2倍以上。我们已经扩展了这些基因的特征。

Abused drugs produce long-lasting changes in behaviors via biochemical mechanisms that are largely unknown. Drug-altered changes in expression of specific genes in the brain can provide a major window on possible biochemical substrates for ddiction. To further explore this area, we are now increasingly focused on array hybridization techniques that has allow identification of dozens of distinct cDNAs that correspond to candidate drug- regulated genes expressed in brain. During this year, we have enhanced characterization of candidate genes whose expression is regulated by amphetamine, cocaine and morphine. We can compare these data to results from knockout mice that lack single- or multiple-genes for receptors and transporters. Using microarrays, we have been able to detect reproducible positive hybridization signals from ca 38% of the genes sampled oligonucleotide DNA microarrays, and to identify the ca 1-2% that are reproducibly regulated more than 2-fold by knockouts or drugs. We have extended characterization of these genes.