GENES REGULATED BY ABUSED DRUGS

滥用药物通过生化机制产生持久的行为变化，这些机制在很大程度上是未知的。药物改变大脑中特定基因表达的变化可以为成瘾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，我们已经建立和开发了消减差异显示，现在越来越多地集中在阵列杂交技术，允许识别几十个不同的cDNA，对应于候选药物调控基因在大脑中表达。在这一年中，我们加强了对那些表达受安非他明、可卡因和吗啡调控的候选基因的表征，并开始将这些数据与缺乏吗啡、可卡因和安非他明主要受体位点的基因敲除小鼠的数据进行比较。使用微阵列，我们已经能够从6800个基因微阵列上采样的约38%的基因中检测到良好的杂交信号，并识别出被敲除或药物调节超过2倍的2-3%。- 差异显示阵列杂交NrCAM钙调神经磷酸酶Gbeta 1可卡因苯丙胺吗啡

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 addiction. To further explore this area, we have established and developed subtracted differential display and are now increasingly focused on array hybridization techniques that has allowed 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 and begun to compare these dta to data from knockout mice that lack major receptor sites for morphine, cocaine and amphetamine. Using microarrays, we have been able to detect good hybridizaiton signals from ca 38% of the genes sampled on 6800 gene microarrays, and to identify the 2-3% that are regulated more than 2-fold by knockouts or drugs. - differential display array hybridization NrCAM calcineurin Gbeta1 cocaine amphetamine morphine