Genetic influences underlying impulsivity and risk for drug addiction

尽管进行了密集的研究工作，但我们仍然不明白为什么有些人使用或依赖强效可卡因等药物，我们也没有有效的治疗方法来预防或改善这种普遍存在的、使人虚弱的大脑疾病。毒品成瘾原因的一个重要线索是，它往往与天生冲动或喜欢冒险的人有关，以及被诊断为患有某些儿童大脑障碍的人，如注意力缺陷多动障碍(ADHD)。这些特征和障碍似乎通过影响成瘾途径的不同阶段，包括首次接触毒品的机会、从偶尔使用药物到定期使用药物的过渡以及反复吸毒和戒毒的倾向，在决定未来问题药物使用的可能性方面发挥重要作用。这项研究使用一种复杂的基因搜索技术来研究这些特征的生物学基础，以确定近亲家庭成员吸毒成瘾的遗传风险。我们的研究将使用一群冲动的老鼠进行，这些老鼠形成吸毒习惯的风险大大增加。我们将在整个老鼠的遗传密码中搜索10,000多个已知的基因变异，以精确定位导致冲动特征的基因。通过这样做，我们将对药物成瘾风险的遗传基础提供更全面的理解，不仅在我们的老鼠模型中，在人类中也是如此。这项研究将有助于发现新的大脑机制和治疗药物滥用和成瘾以及ADHD和相关大脑疾病的方法。

Despite intensive research efforts we still do not understand why some people use or become dependent on drugs such as crack cocaine nor do we have effective treatments to prevent or ameliorate this widespread and debilitating brain disorder. An important clue to the cause of drug addiction is that it tends to be associated with people who are naturally impulsive or who enjoy taking risks, as well as people diagnosed with certain childhood brain disorders such as attention deficit hyperactivity disorder (ADHD). Such traits and disorders appear to play an important role in determining the likelihood of future problem drug use by influencing the various stages of the pathway to addiction, including the chances of first coming into contact with drugs, the transition from occasional to regular drug use and the propensity for repeated episodes of drug binging and withdrawal. This research investigates the biological basis of such traits using a sophisticated gene hunting technique to determine the hereditary risk for drug addiction in close family members. Our research will be conducted using a colony of impulsive rats which carry a strongly increased risk for developing a drug taking habit. We will search over 10,000 known gene variations across the entire rat genetic code to pinpoint genes that underlie the impulsive trait. In so doing, we will provide a much fuller understanding of the genetic basis of risk for drug addiction, not only in our rat model but also in humans. This research will facilitate the discovery of new brain mechanisms and therapies to treat drug abuse and addiction as well as ADHD and related brain disorders.