Neuronal Analysis of Cocaine Effects on Cognition

可卡因对认知影响的神经元分析

• 批准号: 7880787
• 负责人: SAMUEL A. DEADWYLER
• 金额: $ 32.31万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7880787
• 关键词: Acute; Affect; Animal Testing; Animals; Behavior; Brain; Brain region; Characteristics; Chronic; Cocaine; Cocaine Abuse; Cocaine Dependence; Cognition; Cognitive; Complex; Decision Making; Dorsal; Drug Addiction; Drug Controls; Effectiveness; Healthcare; Human; Impaired cognition; Individual; Injection of therapeutic agent; Juice; Laboratories; Laboratory Study; Medial; Methods; Modeling; Monkeys; Neurons; Pathway interactions; Performance; Pharmaceutical Preparations; Physiological; Population; Positron-Emission Tomography; Prefrontal Cortex; Primates; Probability; Procedures; Process; Psyche structure; Psychological reinforcement; Research Personnel; Research Project Grants; Rewards; Sampling; Short-Term Memory; Signal Transduction; Sleep; Sleep Deprivation; Societies; Stress; Structure; Task Performances; Temporal Lobe; Testing; Time; Ventral Striatum; Work; Workplace; addiction; base; cocaine exposure; cocaine use; cognitive function; coping; drug abuse prevention; executive function; expectation; functional group; information processing; insight; nonhuman primate; pressure; programs; reinforcer; relating to nervous system; stressor

DESCRIPTION (provided by applicant): The purpose of this research project is to assess the manner in which information processing in brain structures of nonhuman primates is re-organized by the introduction of and sustained exposure to cocaine as a reinforcer for complex cognitive tasks. It has long been implicitly assumed in analyses of human drug addiction that substances which are abused somehow take over normal reinforcement mechanisms in the brain, diverting such "reward pathways" to the control of drug seeking activities. Using a well-characterized short-term memory/executive function paradigm (multi-object delayed match to sample [DMS] task) studies will determine how cognitive processing is affected by acute and longterm exposure to cocaine as a reinforcer in this task. This primate model of cognitive function has been characterized in recent PET imaging and electrophysiological recording studies from this laboratory. On the basis of that work three important brain regions, medial temporal lobe (MTL), dorsal prefrontal cortex (DPFC) and the dorsal and ventral striatum (D/VStr), shown to be engaged during task performance, will be assessed for effects of cocaine on cognitive processing. Aim 1 will determine neuronal firing characteristics in these three brain regions associated with performance of the DMS task and will identify single neuron correlates of low vs. high cognitive load trials. Aim 2 will examine how these neural correlates change when the task is performed for cocaine injections delivered as the trial reinforcer in comparison to normal appetitive (juice) rewards. Aim 3 will extend the above analyses to animals that are repeatedly exposed to conditions in which cocaine and juice reinforcers are implemented in the same random manner during day-to-day testing for a period of six months in order to assess cumulative changes in DMS responding and associated neuronal correlates over a time period in which performance is sustained at criterion levels by both reinforcers. The final Aim 4 will assess the effects of stress on cocaine vs. juice reinforced DMS performance and associated neural correlates of cognitive load (Aim 1), induced by a method of sleep deprivation perfected for nonhuman primates in this laboratory. Relevance: In a society that is evolving more and more toward increased stress and demand on its citizens the individual level of cocaine abuse is a major health care problem. Such behavior eventually results in inability of the addict to cope with the complex nuances of a complex technologically-based work place. Turning to drugs is a natural course of action for pressured, overworked and under employed personnel.How cocaine use advances to addiction in this context is directly related to effects on cognition, reasoning and decision making. Therefore understanding how cocaine modulates and gradually over time eliminates effective cognitive processing, as studied here, is of primary importance in the prevention of drug addiction.

描述（由申请人提供）：该研究项目的目的是评估通过引入和持续接触可卡因作为复杂认知任务的强化剂，非人类灵长类动物大脑结构中信息处理的重组方式。长期以来，在对人类毒瘾的分析中，人们一直隐含地假设，被滥用的物质以某种方式接管了大脑中的正常强化机制，将这种“奖励途径”转向对药物寻求活动的控制。使用特征明确的短期记忆/执行功能范式（多对象延迟匹配样本 [DMS] 任务）研究将确定认知处理如何受到急性和长期接触可卡因作为该任务的强化剂的影响。该实验室最近的 PET 成像和电生理记录研究已对这种灵长类认知功能模型进行了表征。在此工作的基础上，将评估三个重要的大脑区域，即内侧颞叶（MTL）、背侧前额叶皮层（DPFC）以及背侧和腹侧纹状体（D/VStr），这些区域在任务执行过程中发挥着作用，将评估可卡因对认知处理的影响。目标 1 将确定这三个大脑区域中与 DMS 任务执行相关的神经元放电特征，并将识别低认知负荷试验与高认知负荷试验的单个神经元相关性。目标 2 将检查当执行可卡因注射作为试验强化剂的任务时，与正常的食欲（果汁）奖励相比，这些神经相关性如何变化。目标 3 将把上述分析扩展到在为期六个月的日常测试中以相同随机方式重复暴露于可卡因和果汁强化剂的条件下的动物，以评估在两种强化剂将表现维持在标准水平的一段时间内 DMS 反应和相关神经元相关性的累积变化。最终目标 4 将评估压力对可卡因与果汁增强 DMS 表现的影响以及认知负荷的相关神经相关性（目标 1），这是由本实验室针对非人类灵长类动物完善的睡眠剥夺方法引起的。 相关性：在一个公民压力和需求日益增加的社会中，可卡因滥用的个人水平是一个主要的医疗保健问题。这种行为最终导致成瘾者无法应对复杂的技术工作场所的复杂细微差别。对于压力大、工作过度和就业不足的人员来说，转向毒品是一种自然的行为方式。在这种情况下，使用可卡因如何导致成瘾，与对认知、推理和决策的影响直接相关。因此，正如本文所研究的，了解可卡因如何调节并随着时间的推移逐渐消除有效的认知处理对于预防药物成瘾至关重要。