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，包括初始药物敏感性、耐受性、致敏性、长期使用和复发，直到最近才通过分子分析得以阐明。数量性状位点（QTL）方法的应用使得这些多基因性状调控基因的定位成为可能。此外，转基因小鼠和诱导诱变技术允许研究单基因操作对药物诱导的行为和生理功能改变的影响。qtl定位于吗啡偏好、酒精敏感性、耐受性和戒断。虽然我们对药物强化背后的神经生物学回路有相当多的了解，但对基因多态性知之甚少，这种基因多态性可能介导调节强化和奖励的重要神经基质基因的个体差异。表型的异质性使得酒精和药物滥用人群的基因定位特别困难。通过将目前对可能使个人倾向于药物使用和滥用的遗传因素的了解与动物模型中的生物学和分子研究相结合，将取得进展。会议将涵盖酒精、可卡因、尼古丁和阿片类药物依赖和滥用基因图谱方面的重要突破。一个讲习班将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，作为对最近数据的介绍和讨论的补充。本次研讨会将包括在哺乳动物和无脊椎生物中使用化学诱导突变和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.