Global changes in gene expression during sensitization

致敏过程中基因表达的整体变化

• 批准号: 6445720
• 负责人: KEVIN A LEASE
• 金额: $ 3.48万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-10-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6445720
• 关键词: Drosophilidae; behavioral genetics; behavioral habituation /sensitization; crack cocaine; decarboxylases; drug addiction; fusion gene; gene expression; gene mutation; genetic transcription; genetic transduction; microarray technology; nucleic acid hybridization; nucleic acid quantitation /detection; phenotype; polymerase chain reaction; serial analysis of gene expression; statistics /biometry

Drug addiction is linked to behavioral sensitization in several animal models and humans. Changes in the expression levels of several genes have been shown to correlate with exposure to cocaine or other drugs of abuse in vertebrates. The fruit fly Drosophila melanogaster has been shown to sensitize to intermittent exposure to volatile free base ?crack? cocaine. To test the hypothesis that changes in gene expression are necessary and sufficient for sensitization, global changes in gene expression in the fly brain that occur during sensitization to cocaine will be analyzed by a microarray approach. Further, mutants will be identified for those genes whose levels of transcript correlate with sensitization, to test whether they are required for sensitization. Finally, overexpression of these genes will be tested for their effects on the expression of behavioral sensitization. The results of these studies should shed light on the molecular basis of sensitization to drugs of abuse. This information could lead to new pharmacological targets for treatment of drug addiction.

吸毒成瘾与几种动物模型中的行为敏化有关 和人类。已经显示了几个基因的表达水平的变化 与接触可卡因或其他脊椎动物中的滥用药物有关。 果蝇果蝇melanogaster已被证明对 间歇性暴露于挥发性的自由基地？裂缝？可卡因。测试 假设基因表达的变化是必要而足够的 敏化，苍蝇大脑中基因表达的全球变化 在对可卡因的敏化期间，将通过微阵列方法分析。 此外，将为那些转录本水平的基因确定突变体 与敏化相关，以测试是否需要 致敏。最后，将测试这些基因的过表达 对行为敏化表达的影响。这些结果 研究应阐明敏化对药物的分子基础 虐待。这些信息可能导致新的药理学目标 吸毒成瘾。