Impulsivity and D2 Receptor Function: Behavioral and PET Correlates

冲动性和 D2 受体功能：行为和 PET 相关性

基本信息

批准号：
8246495
负责人：
Stephanie Mary Groman
金额：
$ 3.48万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8246495
关键词：
Affinity Agonist Behavior Behavioral Binding Blinking Brain Brain region Cerebrum Cognition Cognitive Corpus striatum structure Decision Making Deoxyglucose Development Disease Dopamine Dopamine Agonists Dopamine D2 Receptor Dose Drug abuse Economics Exhibits Family Imaging Techniques Impulsivity Individual Individual Differences Intake Investigation Laboratories Lead Left Link Measurement Measures Mediating Molecular Molecular Conformation Monkeys Patient Self-Report Pharmaceutical Preparations Phenotype Population Positron-Emission Tomography Prevention strategy Process Risk Role Short-Term Memory Societies Substance Addiction Substance abuse problem Synapses System Techniques Temperament Variant base behavior measurement biobehavior biological systems caudate nucleus cognitive control dopamine system flexibility functional outcomes glucose metabolism in vivo insight neuroimaging neuromechanism nonhuman primate pre-clinical research radioligand receptor receptor expression receptor function relating to nervous system research study response social trait treatment strategy

项目摘要

DESCRIPTION (provided by applicant): The economic and social burdens on society that are a direct result of substance dependence are enormous. As such, determining the neural mechanisms of phenotypes that confer risk for the development of this disorder is crucial for advancing scientifically-based prevention and treatment strategies. Associations between variation in cognitive processes and substance dependence liability have been demonstrated, and the corticostriatal dopamine system has been implicated in these relationships. Further, recent evidence has demonstrated an important role of the dopamine D2 receptor in controlling aspects of impulsivity, cognitive control and drug abuse. Therefore, the D2 receptor may represent a mechanistic link between cognitive control processes and risk for the development of substance dependence. Because the D2 receptor can exist in two conformational states - a state in which dopamine displays high affinity for the receptor and has greater functional activity, and a state in which dopamine displays less affinity for the receptor and is less functionally active - determining whether variation in receptor availability detected with standard neuroimaging techniques (i.e. PET) reflect variation in receptor state (high versus low) is critical to understanding the relationship between cognitive processes and risk for substance dependence. Because we have found an association between a naturally occurring variation of trait impulsivity and D2 radioligand binding in vivo, this proposal will attempt to examine this question using behavioral pharmacological techniques to probe D2-like receptor states (Aim 1) and using this information to examine a possible neural mechanism by which variation in receptor state may influence global brain function (Aim 2). These results will provide evidence for a mechanism by which variation within a biological system can influence higher- order processes that have direct relevance to substance dependence. The advancements in the characterization of the link between the D2 receptor system and impulsivity offered in this proposal will provide an important step in understanding how manipulations of the dopamine system may be utilized to enhance cognitive control and therefore mitigate risk for the development of substance dependence.

描述（由申请人提供）：社会上依赖物质的直接结果的经济和社会负担是巨大的。因此，确定赋予这种疾病发展风险的表型的神经机制对于推进基于科学的预防和治疗策略至关重要。已经证明了认知过程变化与物质依赖责任之间的关联，并且皮质纹状体多巴胺系统与这些关系有关。此外，最近的证据表明，多巴胺D2受体在控制冲动，认知控制和药物滥用方面的重要作用。因此，D2受体可以代表认知控制过程与产生物质依赖性的风险之间的机械联系。 Because the D2 receptor can exist in two conformational states - a state in which dopamine displays high affinity for the receptor and has greater functional activity, and a state in which dopamine displays less affinity for the receptor and is less functionally active - determining whether variation in receptor availability detected with standard neuroimaging techniques (i.e. PET) reflect variation in receptor state (high versus low) is critical to understanding the relationship between cognitive processes and物质依赖的风险。由于我们发现了体内的自然发生的性格冲动性变化与D2辐射型结合之间存在关联，因此该建议将尝试使用行为药理技术来检验这个问题，以探测D2样受体状态（AIM 1）（AIM 1）（AIM 1），并使用此信息来检查受体状态中可能的神经机制，从而影响全球脑功能（AIM 2）。这些结果将提供证据证明一种机制，通过这种机制，生物系统内的变异可以影响与物质依赖性直接相关的高阶过程。 D2受体系统与本提案中提供的冲动性之间联系的进步将为理解如何利用多巴胺系统的操纵来增强认知控制，从而减轻对物质依赖的发展的风险。