INBRED AND RECOMBINANT INBRED STRAIN COMPARISONS AND BIOCHEMICAL CORRELATES

在人类和动物之间有很大的个体差异 对滥用药物的行为、生理和毒理学反应。 这些个体对药物的行为反应的差异也 显示出巨大的遗传和环境影响，是 持续分布，似乎受到许多基因的影响 而不是一两个主要基因。出于这些原因，适用于 遗传学和分子生物学的几项技术可能是 有助于识别易于研究的遗传影响 可以揭示人类个体间关系的实验动物 差异，并确定潜在的负责行为的基因 这些动物的药物反应的变化。 重组近交系菌株已被测试可卡因诱导的运动 反应、致敏和F2小鼠识别相关基因座 具有这些表型。来自异种种群的动物一直是 测试可卡因诱导的运动激活，并已被用于 建立基因选择范式，询问选择是否 可卡因诱导的运动也可以选择其他可卡因诱导的运动 功能，包括精神运动刺激剂条件性位置偏爱 措施。这些方法中的每一种都将改进对 药物滥用中的遗传影响及重组人的分析 近亲交配品系的比较将允许对特定的 通过数量性状影响品系差异的基因 轨迹接近了。

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.