GENETIC APPROACHES TO CHARACTERIZING DRUG RESPONSES AND VULNERABILITIES

表征药物反应和脆弱性的遗传学方法

• 批准号: 2571616
• 负责人: G R UHL
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2571616
• 关键词: animal genetic material tag; behavioral genetics; behavioral habituation /sensitization; cocaine; genetic mapping; genetically modified animals; laboratory mouse; pharmacogenetics; preference; psychomotor function; psychopharmacology; substance abuse related disorder

There are large individual differences among humans and animals in behavioral, physiological and toxicological responses to drugs of abuse. These individual differences in behavioral responses to drugs also display substantial genetic and environmental influences, are continuously distributed, and appear to be influenced by many genes rather than one or two major genes. For these reasons, application of several of the techniques of genetics and molecular biology could be helpful in identification of genetic influences in readily-studied experimental animals that could shed light on human interindividual differences, and identify genes potentially responsible for behavioral variation in drug responses in these animals. Recombinant inbred strains have been tested for cocaine-induced locomotor responses, sensitization and F2 mice to identify gene loci associated with these phenotypes. Animals from a heterogenous stock have been tested for cocaine-induced locomotor activation, and have been used to establish a genetic selection paradigm to ask if selection for cocaine- induced locomotion also selects for other cocaine-induced functions, including psychomotor stimulant conditioned place preference measures. Each of these approaches will allow improved assessment of genetic influences in substance abuse, and analyses of the recombinant inbred strain comparisons will allow chromosomal mapping of specific genes contributing to the strain differences through quantitative trait locus approaches.

人和动物之间存在很大的个体差异 对滥用药物的行为、生理和毒理学反应。 这些对药物行为反应的个体差异也 显示出显着的遗传和环境影响，是 连续分布，并且似乎受到许多基因的影响 而不是一两个主要基因。 由于这些原因，应用 遗传学和分子生物学的一些技术可以 有助于识别易于研究的遗传影响 实验动物可以揭示人类个体之间的关系 差异，并识别可能导致行为的基因 这些动物的药物反应存在差异。 重组近交系已测试可卡因诱导的运动能力 反应、致敏和 F2 小鼠以确定相关基因位点 与这些表型。 来自异质种群的动物已被 测试可卡因诱导的运动激活，并已用于 建立一个遗传选择范式来询问可卡因的选择是否 诱导运动还选择其他可卡因诱导的功能， 包括精神运动兴奋剂条件性位置偏好措施。 这些方法中的每一种都将有助于改进遗传评估 药物滥用的影响以及重组近交系的分析 菌株比较将允许特定基因的染色体作图 通过数量性状基因座促进品系差异 接近。