VULNERABILITY TO DRUG ABUSE--PREVALENCE OF DA RECEPTORS

每个人对药物滥用的易感性似乎各不相同。 人类的奖赏系统由多巴胺能(DA)组成。 神经元和成瘾药物的管理导致 对这一系统的刺激。一个合理的假设 药物滥用的神经化学基础是易受伤害的个体 自我用药来弥补多巴胺能奖赏的缺陷 系统。来研究基因变异是否有可能 不同形式的多巴胺D2受体(DRD2)的流行 吸毒者的基因可能与药物易感性有关 上瘾，我们确定了DRD2变异体在 数百名药物滥用者。这显示出高度的相关性 TaqI A1变异体的频率与多物质 滥用，根据每种药物超过25美元的数量 用药时间为1周(p=0.006)。使用防御方式问卷， 携带L单倍型的吸毒者，这是连锁的 与D2A1变种的不平衡，显示出更多的使用 不成熟的防御比非1携带者。 这些初步研究支持这样一个概念，即 DA受体变异体的流行在 影响一个人脆弱程度的基本人格特征 滥用药物，以及其他冲动、强迫、上瘾 行为。为了尝试验证这种关联，我们建议使用 根据对200名男性药物滥用者的研究，来自 曾傑瑞L.佩蒂斯V.A.医院戒毒病房和 性别、年龄、种族和民族匹配的对照：L)遗传 DRD2的D2A1、B1、C1和单倍型变异的检测 基因，2)多巴胺D1、D3、D4变异体的基因检测 和D5受体基因和多巴胺转运蛋白基因检测 在所有有诊断性面谈时间表的基因分型受试者中， MMP1、成瘾严重程度指数、防御方式问卷 Axis II人格指数。4)要测试的统计分析 独立遗传变量之间的可能相关性， 人格变量和药物滥用。

Individuals appear to vary in their vulnerability to drug abuse. The reward system in humans is composed of dopaminergic (DA) neurons and the administration of addicting drugs results in the stimulation of this system. A reasonable hypothesis for the neurochemical basis of drug abuse is that vulnerable individuals self medicate to compensate for defects in the dopaminergic reward system. To investigate the possibility that variations in the prevalence of different forms of the dopamine D2 receptor (DRD2) gene in drug addicts may be involved in the vulnerability to drug addiction, we determined the frequency of the DRD2 variants in several hundred substance abusers. This showed a high correlation between the frequency of the TaqI A1 variant and multisubstance abuse, based upon the number of drugs on which more than $25 per week were spent, (p= 0.006). Using the Defense Style Questionnaire, drug addicts carrying the l haplotype, which is in linkage disequilibrium with the D2A1 variant, showed much greater use of immature defenses than non-1 carriers. These preliminary studies support the concept that differences in the prevalence of DA receptor variants play an important role in fundamental personality traits that affect a person's vulnerability to drug abuse, and other impulsive, compulsive, addictive behaviors. To attempt to verify this association, we propose the following studies on 200 male substance abusers, from the Addictions Treatment Ward at the Jerry L. Pettis V.A. Hospital and 200 sex age, race, and ethnically matched controls: l) Genetic testing of the D2A1, B1, C1 and haplotype variants of the DRD2 gene, 2) Genetic testing for variants of the dopamine D1, D3, D4 and D5 receptor genes and the dopamine transporter gene 3) Testing of all genotyped subjects with the Diagnostic Interview Schedule, MMP1, Addiction Severity Index, Defense Style Questionnaire and Axis II Personality Index. 4) Statistical analysis to test for possible correlations between the independent genetic variables, personality variables and drug abuse.