Neurobiological correlates of trait impulsivity and drug abuse vulnerability

越来越多的人认识到，社会上的许多人显然可以长期使用可卡因等药物，而不会对药物产生依赖。例如，据估计，只有不到20%的吸食可卡因的人真正上瘾；换句话说，毒品消费模式不断升级，不顾不良后果(如婚姻和家庭破裂、失业、健康不佳和监禁的威胁)持续吸食毒品，最终失去对药物摄入量的控制。最近的研究还表明，某些人格特征(例如，追求感觉和新奇的人)，以及被诊断为注意力缺陷多动障碍(ADHD)、抑郁症和其他大脑疾病的人，更有可能滥用药物，最终发展到毒瘾的晚期阶段。这项研究的重点是与某些人格特征相关的大脑化学潜在异常，并调查这些变化如何使人容易滥用药物和成瘾。将使用一种强大的非侵入性脑成像技术(正电子发射断层扫描或？PET？)将大脑中特定的化学感受器可视化，先前的研究已将其与某些冲动特征(即计划和控制不善、未经适当考虑或预见而发生的行为)以及可卡因和其他滥用药物对大脑的长期影响联系起来。我们的具体目标是阐明与表现出高水平冲动行为的个人的可卡因成瘾风险增加有关的大脑机制？ADHD的核心症状？从而解决为什么这些人更有可能对可卡因和其他滥用药物上瘾。这项研究的一个关键是，我们能够在同一个人身上评估从第一次接触毒品到出现吸毒成瘾行为的过程，从而确定大脑化学的变化，这些变化可能是从娱乐用药向反复使用和成瘾转变的基础。这项研究对于了解ADHD和药物成瘾的神经生物学及其相互关系，从而发现治疗这些衰弱和经常合并的大脑疾病的新方法具有重要意义。它还解决了一个有争议的问题，即？悖论？用哌醋甲酯(或利他林？)等兴奋剂治疗ADHD改变了从随意使用药物到强制使用药物的进程，从而使新疗法的开发成为可能。

It is becoming increasingly recognised that many people in society can apparently use drugs such as cocaine for prolonged periods of time without ever becoming dependent on the drug. For example, it has been estimated that less than 20% of people who use cocaine actually become addicted; or in other words, show an escalating pattern of drug consumption, a persistence of drug taking despite adverse consequences (e.g., marital and family breakdown, unemployment, ill health and the threat of incarceration) and ultimately a loss of control over drug intake. Recent research also indicates that certain personality traits (e.g., sensation- and novelty-seekers), as well as people diagnosed with attention-deficit hyperactivity disorder (ADHD), depression and other brain disorders, are more likely to abuse drugs and progress ultimately to the advanced stages of drug addiction. This research focuses on underlying abnormalities in brain chemistry associated with certain personality traits and investigates how these changes confer vulnerability for drug abuse and addiction. A powerful non-invasive brain imaging technique will be used (positron emission tomography or ?PET?) to visualise a particular chemical receptor in the brain which previous research has linked to certain impulsive traits (i.e., behaviour that is poorly planned and controlled and occurs without due consideration or foresight), as well as the long-term effects of cocaine and other drugs of abuse on the brain. Our specific objective is to elucidate the brain mechanisms associated with the increased risk for cocaine addiction of individuals showing high levels of impulsive behaviour ? a core symptom of ADHD ?and thereby address why these individuals are more likely to become addicted to cocaine and other drugs of abuse. A key to this research is that we are able to assess in the same individual the progression from first drug exposure to the emergence of drug addictive behaviour, thereby determining changes in brain chemistry that potentially underlie the transition from recreational drug use to repeated use and addiction. This research has important implications for understanding the neurobiology of, and inter-relationship between, ADHD and drug addiction and thus in discovering new ways of treating these debilitating and frequently co-morbid brain disorders. It also addresses the contentious issue whether the ?paradoxical? treatment of ADHD with stimulant drugs such as methylphenidate (or Ritalin?) alters the progression from casual to compulsive drug use, thereby enabling the development of novel therapies.