GENES REGULATED BY ABUSED DRUGS

滥用药物通过在很大程度上不为人所知的生化机制，在行为上产生长期的变化。药物改变大脑中特定基因的表达变化，可以为吸毒的可能生化底物提供一个主要窗口。为了进一步探索这一领域，我们现在越来越关注阵列杂交技术，它可以识别数十个与大脑中表达的候选药物调控基因相对应的不同的cDNA。在这一年里，我们加强了候选基因的特征，这些基因的表达受到苯丙胺、可卡因和吗啡的调控。我们可以将这些数据与缺乏单一或多个受体和转运蛋白基因的基因敲除小鼠的结果进行比较。使用微阵列，我们已经能够从抽样的寡核苷酸DNA微阵列中检测到约38%的可重复的阳性杂交信号，并识别出被敲除或药物重复调控2倍以上的约1-2%的基因。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.