Imaging Research on Impulsivity, Stress and Drug Abuse

摘要 在过去的十年中，神经成像技术已经扩大了关于滥用药物对神经系统的影响的知识。 大脑神经回路，并提供了工具，以增加我们的理解，这些电路发挥的作用 动机行为和物质使用障碍。然而，我们的知识中存在着一个持续的差距， 从试图确定大脑神经化学的改变是否代表 吸毒成瘾者的脆弱性因素或成瘾后果。一个挑战性的问题， 困扰这个领域的是为什么有些人在生理上比其他人更容易上瘾。两个因素 与临床上物质使用障碍的发展和过程密切相关， 研究是冲动和环境压力。越来越多的临床前研究证据表明， 这些因素可能与多巴胺（DA）神经传递的改变有关。这些发现， 加上明确的证据表明DA参与药物滥用，表明冲动， 慢性应激和药物滥用可能由DA系统介导。然而，这些问题的性质 对人际关系的了解仍然很少，也缺乏人类研究。在拟议的研究中，我们将使用PET 技术，以评估DA功能的特定改变是否早于人类药物滥用， 增加了发生吸毒障碍的风险。具体来说，我们将研究纹状体DA 在健康的年轻人中，对安非他明的反应与冒险行为或慢性压力有关 没有药物滥用或依赖史参与者将完成一项实验室表演 风险行为评估和两次[11 C]雷氯必利PET扫描测量个体 安非他明诱导的DA释放的差异。生活事件压力的措施也将获得。 次要目的包括探索性分析与其他低阶维度的关联， 冲动和早期生活压力。我们假设多巴胺活性的降低是脑缺血的危险因素。 药物使用障碍的发展以及冒险和长期紧张会增加药物滥用的风险 通过这个机制。项目叙述 通过增加我们对介导脆弱性物质使用的离散神经过程的理解， 这些发现将有助于正在进行的新的和有希望的预防和治疗疾病的发展， 考虑到遗传和环境脆弱性的根本差异的治疗策略 个人之间的因素。

Abstract In the past decade, neuroimaging technology has expanded knowledge about the effects of drugs of abuse on brain neurocircuitry and has provided tools for increasing our understanding of the role that these circuits play in motivational behaviors and substance use disorders. Nevertheless, a persistent gap in our knowledge stems from the difficulties involved in trying to determine whether alterations in brain neurochemistry represent vulnerability factors or consequences of addiction in drug addicts. A challenging question that continues to plague this field is why some individuals are biologically more vulnerable to addiction than others. Two factors that have been strongly associated with the development and course of substance use disorders in clinical studies are impulsivity and environmental stress. There is growing evidence from preclinical studies that each of these factors may be associated with alterations in dopamine (DA) neurotransmission. These findings, coupled with clear evidence of DA involvement in drug abuse, suggest that relationships among impulsivity, chronic stress, and drug abuse may be mediated by the DA system. Nevertheless, the nature of these relationships is still poorly understood and human studies are lacking. In the proposed study, we will use PET technology to evaluate whether specific alterations in DA function predate drug abuse in humans and may increase risks for the development of drug use disorders. Specifically, we will examine whether striatal DA responses to amphetamine are associated with risk taking behavior or chronic stress in healthy, young adults with no history of substance abuse or dependence. Participants will complete a laboratory performance assessment of risk taking behavior and two [11C]raclopride PET scans measuring individual differences in amphetamine-induced DA release. Measures of life events stress will also be obtained. Secondary aims include exploratory analysis of associations with other lower-order dimensions of impulsivity and with early life stress. We hypothesize that dampened DA activity is a risk factor for the development of substance use disorders and that risk taking and chronic stress increase risks for drug abuse through this mechanism. Project Narrative By increasing our understanding of discrete neural processes that mediate vulnerability substance use disorders, the findings will contribute to the ongoing development of new and promising prevention and treatment strategies that take into account fundamental differences in genetic and environmental vulnerability factors across individuals.