Methamphetamine effect on cognitive flexibility

甲基苯丙胺对认知灵活性的影响

• 批准号: 7625357
• 负责人: Alicia Izquierdo
• 金额: $ 14.45万
• 依托单位: CALIFORNIA STATE UNIVERSITY LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7625357
• 关键词: Adopted; Affect; Age; Alcohols; Amygdaloid structure; Animal Model; Animals; Attention; Behavior; Behavioral; Brain; Buffers; Choice Behavior; Classification; Cocaine Abuse; Cognition; Cognitive; Computer software; Data; Decision Making; Development; Dose; Drug usage; Equipment; Event; Exercise; Extinction (Psychology); Food; Foundations; Future; Genetic; Goals; Heroin; Human; Impaired cognition; Impairment; Incentives; Investigation; Knowledge; Learning; Left; Marijuana; Marshal; Measures; Mediating; Memory; Mentorship; Methamphetamine; Methodology; Methods; Monkeys; Motivation; Neurobiology; Neurologic; Neurons; Neuropharmacology; Neurosciences Research; Organism; Pathway interactions; Performance; Pharmaceutical Preparations; Pilot Projects; Prefrontal Cortex; Principal Investigator; Procedures; Process; Public Health; Rattus; Reaction Time; Relapse; Relative (related person); Research; Research Personnel; Reversal Learning; Rewards; Rodent; Role; Serotonin; Solid; Stimulus; Stress; Stress and Coping; System; Testing; Training; Treatment Protocols; United States; Variant; Work; addiction; base; behavior test; cognitive neuroscience; drug of abuse; executive function; experience; flexibility; hedonic; innovation; learning extinction; methamphetamine abuse; monoamine; neural circuit; neurobiological mechanism; neurotoxic; nonhuman primate; novel; post-doctoral training; psychostimulant; public health relevance; research study; response; serotonin transporter; stimulant abuse; success; therapeutic target; tool; touchscreen; two-dimensional

DESCRIPTION (provided by applicant): Methamphetamine (mAMPH) is a highly addictive psychostimulant. In many regions of the United States, it is second only to alcohol and marijuana as the most frequently used drug, often outpacing both heroin and cocaine abuse. Despite an increased number of studies recently devoting attention to measuring mAMPH effects on learning and memory, no systematic investigation has been conducted on mAMPH's impact on cognitive flexibility in either an animal model or in humans. Cognitive flexibility is of vital importance to the success of an organism and refers to the ability to shift strategy given a new set of circumstances. If mAMPH impacts functioning of the orbitofrontal cortex (OFC), as is currently posited, then mAMPH likely has an impact on flexible cognition. In addition, there is now evidence for serotonergic modulation of this flexible cognition and given that neuronal serotonin integrity is compromised in mAMPH abusers (and mAMPH-treated animals), this is a timely issue. We propose to study the effects of mAMPH on flexible cognition using a touch screen-based operant procedure sensitive to pharmacological manipulation in rodents. Our measures of flexible cognition are reversal learning and extinction, two separate tasks sensitive to both OFC recruitment and serotonergic modulation and that are well-equipped with a host of auxiliary measures of motivation, attention, and inhibitory control. Our long-term goal is to reconcile our understanding of the neural circuitry that subserves flexible cognition with the pathological effects of drugs of abuse. To begin to accomplish our long-term goal, two specific aims are proposed: 1) to establish baseline cognitive flexibility performance in untreated rats and 2) to compare the effects of a binge regimen and an escalating, neuroprotective dose regimen of mAMPH on cognitive flexibility and the OFC. Results arising from this project will enhance our understanding of the impact of mAMPH on flexible cognitive processes and increase our ability to identify therapeutic targets to ameliorate the poor decision making arising from mAMPH abuse. At best, a rescued cognitive flexibility could aid mAMPH addicts in remaining abstinent. Public Health Relevance: Methamphetamine is a highly addictive psychostimulant and a growing public health concern, with a record of nearly 1.4 million people over the age of 12 using methamphetamine in the United States in 2005. Those addicted to this substance make poor, disadvantageous choices and relapse often. The long-term goal of this project is to provide knowledge about the effects of methamphetamine on decision making and the brain.

描述（由申请人提供）：甲基苯丙胺（MAMPH）是一种高度上瘾的心理刺激剂。在美国的许多地区，它仅次于酒精和大麻是最常用的药物，通常超过海洛因和可卡因滥用。尽管最近的研究越来越多，致力于测量MAMPH对学习和记忆的影响，但尚未对MAMPH对动物模型或人类认知灵活性的影响进行系统的研究。认知灵活性对于有机体的成功至关重要，并指在新的情况下改变战略的能力。如果MAMPH会影响轨道额皮层（OFC）的功能，那么MAMPH可能会对柔性认知产生影响。此外，现在有证据表明了这种灵活认知的血清素能调节，并且鉴于在MAMPH施虐者（和MAMPH处理的动物）中神经元5-羟色胺完整性受到损害，这是一个及时的问题。我们建议使用对啮齿动物中药理操作敏感的基于触摸屏的操作过程来研究MAMPH对柔性认知的影响。我们的柔性认知度量是逆转学习和灭绝，这是对OFC募集和血清素能调节敏感的两个独立任务，并且配备了许多动机，注意力和抑制性控制的辅助度量。我们的长期目标是调和我们对神经回路的理解，该神经回路将灵活的认知与滥用药物的病理影响相结合。为了开始实现我们的长期目标，提出了两个具体目标：1）在未经处理的大鼠中建立基线认知柔韧性性能，以及2）比较暴饮暴食方案的影响以及MAMPH的升级，神经保护方案对认知灵活性和OFC的效果。该项目产生的结果将增强我们对MAMPH对柔性认知过程的影响的理解，并提高我们确定治疗目标以减轻滥用MAMP的不良决策的能力。充其量，救出的认知灵活性可以帮助蒙普成瘾者保持戒酒。 公共卫生相关性：甲基苯丙胺是一种高度上瘾的心理刺激性，并且在公共卫生的问题上越来越多，在2005年，使用甲基苯丙胺在12岁以上的近140万人中记录了近140万人。那些沉迷于这种物质的人使贫困，劣势选择并经常复发。该项目的长期目标是提供有关甲基苯丙胺对决策和大脑的影响的知识。