GENETICS OF ALCOHOL AND SUBSTANCE ABUSE

调控与药物滥用相关的复杂行为表型的基因的阐明，包括最初的药物敏感性、耐受性、敏化、慢性使用和复发，直到最近才能进行分子分析。数量性状基因座(QTL)方法的应用使得控制这些多基因性状的基因定位成为可能。此外，转基因小鼠和诱变技术可以研究单基因操作对药物诱导的行为和生理功能变化的影响。有关吗啡偏好、酒精敏感性、耐受性和戒断的QTL已被定位。虽然有相当多的知识与药物强化背后的神经生物回路有关，但对调节调节强化和奖励的重要神经底物的基因的个体差异可能起调节作用的遗传多态知之甚少。表型的异质性使得在酒精和药物滥用人群中进行基因定位特别困难。通过将目前对可能使个人易于使用和滥用药物的遗传因素的知识与动物模型中的生物学和分子研究相结合，将取得进展。这次会议将讨论酒精、可卡因、尼古丁、阿片类药物依赖和滥用的基因图谱方面的重要突破。一个介绍尚未广泛应用于酒精和药物滥用等复杂问题的遗传方法的讲习班将补充介绍和讨论最近的数据。这次研讨会将包括在哺乳动物和无脊椎动物生物体中使用化学诱导的突变和RNA差异基因表达技术。

The elucidation of genes regulating the complex behavioral phenotypes related to drug abuse including initial drug sensitivity, tolerance, sensitization, chronic use and relapse have only recently been amenable to molecular analyses. The application of quantitative trait loci (QTL) methods has allowed the mapping of genes regulating these polygenic traits. Moreover, transgenic mouse and inducible mutagenesis techniques allow investigations into the impact of single gene manipulations on drug-induced alterations of behavioral and physiological function. QTLs have been localized for morphine preference, alcohol sensitivity, tolerance, and withdrawal. While there is considerable knowledge pertaining to the neurobiological circuitry underlying drug reinforcement, little is known about the genetic polymorphisms that may mediate individual differences in genes regulating important neural substrates regulating reinforcement and reward. Heterogeniety of phenotype makes gene mapping particularly difficult in the human population for alcohol and substance abuse. By integrating current knowledge of genetic factors that may predispose individuals to drug use and abuse with biological and molecular studies in animal models, advancement will be made. The conference will cover important breakthroughs in the mapping of genes for alcohol, cocaine, nicotine, and opiate dependence and abuse. A workshop presenting genetic methods that have not been widely applied to the complex issues of alcohol and substance abuse will supplement presentations and discussion of recent data. This workshop will include the use of chemically-induced mutations in mamalian and invertebrate organisms and RNA differential gene expression techniques.