GENETIC APPROACHES TO CHARACTERIZING DRUG RESPONSES AND VULNERABILITIES

人类和动物之间存在很大的个体差异， 对滥用药物的行为、生理和毒理反应。 对药物的行为反应的个体差异也 显示出巨大的遗传和环境影响， 连续分布，似乎受到许多基因的影响 而不是一两个主要基因。 因此，应用 遗传学和分子生物学的一些技术可以 有助于识别遗传影响， 可以揭示人类个体间关系的实验动物 差异，并确定可能负责行为的基因 这些动物中药物反应的变化。 重组近交系已被测试可卡因诱导的运动 反应，致敏和F2小鼠，以确定相关的基因位点 这些表型。 来自异种的动物已经被 测试可卡因诱导的运动激活，并已用于 建立一个基因选择的范例来询问是否选择可卡因- 诱导运动也选择其他可卡因诱导的功能， 包括精神刺激条件性位置偏好测量。 这些方法中的每一种都将有助于改善对遗传病的评估。 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对品系差异起作用 接近。

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.