Neuronal Analysis of Cocaine Effects on Cognition

可卡因对认知影响的神经元分析

• 批准号: 7489960
• 负责人: SAMUEL A. DEADWYLER
• 金额: $ 32.63万
• 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/7489960
• 关键词: Acute; Affect; Animal Testing; Animals; Behavior; Brain; Brain region; Characteristics; Chronic; Classification; Cocaine; Cocaine Abuse; Cocaine Dependence; Cognition; Cognitive; Complex; Computer information processing; Condition; Decision Making; Dorsal; Drug Addiction; Drug Controls; Effectiveness; Exposure to; Fire - disasters; 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; Purpose; Rate; Research Personnel; Research Project Grants; Rewards; Sampling; Short-Term Memory; Signal Transduction; Sleep; Sleep Deprivation; Societies; Stress; Structure; Substance Addiction; Task Performances; Techniques; Temporal Lobe; Testing; Time; Ventral Striatum; Work; Workplace; addiction; base; cognitive function; coping; day; drug abuse prevention; executive function; expectation; functional group; 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）：本研究项目的目的是评估非人灵长类动物脑结构中的信息处理通过引入和持续暴露于可卡因作为复杂认知任务的替代品而重组的方式。在对人类药物成瘾的分析中，长期以来一直隐含着这样一种假设：被滥用的物质以某种方式接管了大脑中正常的强化机制，将这种“奖励途径”转向控制寻求药物的活动。使用一个很好的表征短期记忆/执行功能范式（多对象延迟匹配到样本[DMS]任务）的研究将确定如何认知处理的影响，急性和长期暴露于可卡因作为一种替代品，在这个任务。该实验室最近的PET成像和电生理记录研究已经表征了这种认知功能的灵长类动物模型。在这项工作的基础上，三个重要的大脑区域，内侧颞叶（MTL），背侧前额叶皮层（DPFC）和背侧和腹侧纹状体（D/VStr），在任务执行过程中进行，将评估可卡因对认知加工的影响。目标1将确定与DMS任务的表现相关的这三个脑区域中的神经元放电特征，并将识别低与高认知负荷试验的单神经元相关性。目标2将研究这些神经相关性如何变化时，执行任务的可卡因注射交付作为试验兴奋剂相比，正常的食欲（果汁）奖励。目的3将上述分析扩展到反复暴露于可卡因和果汁增敏剂在日常测试期间以相同随机方式实施的条件下持续六个月的动物，以评估DMS响应和相关神经元相关性在一段时间内的累积变化，其中表现由两种增敏剂维持在标准水平。最终目标4将评估压力对可卡因与果汁强化的DMS表现的影响以及认知负荷的相关神经相关性（目标1），这是由本实验室中针对非人灵长类动物完善的睡眠剥夺方法引起的。 相关性：在一个社会中，越来越多地朝着增加的压力和对公民的要求发展，可卡因滥用的个人水平是一个主要的卫生保健问题。这种行为最终导致成瘾者无法科普复杂的技术工作场所的复杂细微差别。转向毒品是一个自然的行动过程中的压力，过度劳累和就业不足的人员。可卡因使用如何在这种情况下发展成成瘾直接关系到对认知，推理和决策的影响。因此，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过程，如本文所研究的，对于预防药物成瘾至关重要。