Imaging Research on Impulsivity, Stress and Drug Abuse

冲动、压力和药物滥用的影像学研究

• 批准号: 7840536
• 负责人: LYNN M OSWALD
• 金额: $ 59.52万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7840536
• 关键词: Accounting; Amphetamines; Arousal; Behavior; Brain; Characteristics; Chronic stress; Clinical Research; Corpus striatum structure; Coupled; Deltastab; Dependence; Development; Dimensions; Disease; Disinhibition; Dopamine; Drug Use Disorder; Drug abuse; Environmental Risk Factor; Esthesia; Event; Genetic; Human; Image; Impulsive Behavior; Impulsivity; Individual; Individual Differences; Knowledge; Laboratories; Life; Life Stress; Long-Term Effects; Measures; Mediating; Nature; Neurobiology; Neurotransmitters; Participant; Pathway interactions; Performance; Personality; Personality Traits; Plague; Play; Positron-Emission Tomography; Predisposition; Prevention; Process; Raclopride; Recording of previous events; Reporting; Research; Rewards; Risk; Risk Factors; Risk-Taking; Role; Serotonin; Stress; Substance Use Disorder; Substance abuse problem; System; Technology; Variant; addiction; disorder risk; dopamine system; drug abuser; drug addict; drug of abuse; neurochemistry; neuroimaging; neurotransmission; pre-clinical; preclinical study; protective effect; public health relevance; relating to nervous system; response; stem; stress related disorder; tool; trait; treatment strategy; young adult

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.

描述（由申请人提供）：在过去的十年中，神经成像技术扩大了有关药物滥用对大脑神经回路影响的知识，并为我们提供了工具，以增加我们对这些回路在动机行为和物质使用障碍中所起作用的理解。然而，我们的知识中存在着一个持续的缺口，这是因为我们很难确定大脑神经化学的改变是否代表了吸毒成瘾者的脆弱性因素或成瘾后果。一个持续困扰这个领域的挑战性问题是，为什么有些人在生物学上比其他人更容易上瘾。在临床研究中，与物质使用障碍的发展和过程密切相关的两个因素是冲动和环境压力。越来越多的临床前研究证据表明，这些因素中的每一个都可能与多巴胺（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，冲动，慢性压力和药物滥用之间的关系可能是由DA系统介导的。然而，这些关系的性质仍然知之甚少，缺乏人类研究。在拟议的研究中，我们将使用PET技术来评估DA功能的特定改变是否早于人类药物滥用，并可能增加药物使用障碍的风险。具体来说，我们将研究纹状体DA反应安非他明是否与冒险行为或慢性压力在健康，年轻的成年人没有药物滥用或依赖的历史。参与者将完成实验室风险行为评估和两次[11 C]雷氯必利PET扫描，测量安非他明诱导的DA释放的个体差异。生活事件压力的措施也将获得。次要目标包括探索性分析与冲动性的其他低阶维度和早期生活压力的关联。我们假设DA活性减弱是药物使用障碍发展的一个风险因素，而冒险和慢性压力通过这种机制增加了药物滥用的风险。公共卫生关系：通过增加我们对介导脆弱性物质使用障碍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前途的预防和治疗策略的开发，这些策略考虑到个体之间遗传和环境脆弱性因素的根本差异。