VULNERABILITY TO DRUG ABUSE--PREVALENCE OF DA RECEPTORS

个人对药物滥用的脆弱性似乎各不相同。 人类的奖赏系统由多巴胺能（DA） 神经元和成瘾药物的管理导致 这一制度的激励。一个合理的假设， 药物滥用的神经化学基础是脆弱的个体 自我调节以弥补多巴胺能奖赏的缺陷 系统为了研究这种可能性， 不同形式的多巴胺D2受体（DRD2）的患病率 药物依赖者的一个基因可能与药物易感性有关 成瘾，我们确定了DRD2变异的频率， 数百名药物滥用者这显示了高度的相关性 TaqI A1变体和多物质的频率之间 滥用，根据药物的数量，超过25美元， 周，（p= 0.006）。使用防御方式问卷， 携带l单倍型的吸毒者， 与D2A1变体的不平衡，显示出更多的使用 不成熟的防御系统。 这些初步研究支持了这样一个概念，即 DA受体变异体流行在 影响一个人脆弱性的基本人格特征 滥用药物，以及其他冲动，强迫，成瘾 行为。为了验证这种关联，我们建议 根据对200名男性滥用药物者的研究， 杰里·L.的成瘾治疗病房佩蒂斯V.A.医院和 200名性别、年龄、种族和人种匹配的对照组： D2A1、B1、C1和DRD2单倍型变体的检测 基因，2）多巴胺D1，D3，D4变体的基因检测 和D5受体基因和多巴胺转运蛋白基因3）测试 在所有具有诊断访谈时间表的基因分型受试者中， MMP1、成瘾严重程度指数、防御方式问卷和 第二轴人格指数。4)统计分析以检验 独立遗传变量之间可能的相关性， 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.