Brain Mechanisms of Avoidance: Implications for Addiction

回避的大脑机制：对成瘾的影响

• 批准号: 9211498
• 负责人: JOSEPH E LEDOUX
• 金额: $ 14.27万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9211498
• 关键词: Addictive Behavior; Amygdaloid structure; Area; Avoidance Learning; Behavior; Behavioral; Brain; Cells; Complex; Conditioned Stimulus; Consumption; Data; Distress; Emotional; Event; Fiber; Freezing; Funding; Grant; Health; Incentives; Injection of therapeutic agent; Lateral; Lead; Learning; Lesion; Light; Link; Literature; Mediating; Methods; Motivation; National Institute of Drug Abuse; Negative Reinforcements; Neurobiology; Neurons; Neurosciences; Nucleus Accumbens; Optics; Pain; Pathway interactions; Pattern; Pharmaceutical Preparations; Pharmacogenetics; Phase; Play; Process; Psychological reinforcement; Reaction; Recording of previous events; Relapse; Research; Research Personnel; Rewards; Role; Shock; Signal Transduction; Specificity; Stimulus; Stress; Structure; Substance abuse problem; Techniques; Technology; Testing; Work; addiction; aversive conditioning; avoidance behavior; base; classical conditioning; conditioned fear; conditioning; designer receptors exclusively activated by designer drugs; discount; drug withdrawal; dysphoria; knowledge base; neuromechanism; optogenetics; relating to nervous system; research study; response; temporal measurement; tool

 DESCRIPTION (provided by applicant): In spite of massive amounts of work, the neural basis of addiction remains only partly understood. Much progress has been made in recent years in understanding the motivational role of drugs as positive incentives and rewards. Although it has long known that aversive motivation also plays a role in addiction, this is less clearly understood. External stimuli associated with environmental stress or drug withdrawal are negative reinforces that contribute to instrumental drug seeking and consumption responses by strengthening behaviors that allow escape from and/or avoidance of the aversive states elicited by these stimuli. Because active avoidance conditioning is based on negative reinforcement and involves brain circuits that overlap with addiction, we argue that a detailed understanding of the neural basis of escape/avoidance behavior will provide important information that may allow a deeper understanding of the role of aversive states in substance abuse. While much research was conducted on the neural basis on avoidance in the 1950s and 60s, this work fell out of favor, in part because the results did not lead to a clear understanding of the circuitry. However, in the intervening years, the neural basis of the first phase of avoidance, Pavlovian fear conditioning, has been elucidated in detail. This information makes it possible to revisit the neural basis of avoidance in a new light. In particular, given that we now understand in detail the neural mechanisms through which a neutral environmental stimulus associated with an aversive unconditioned stimulus (US) becomes a Pavlovian conditioned stimulus (CS) that elicits aversive states, we can now build on this information to understand the neural basis of avoidance conditioning, especially if the same stimuli used as CSs and USs (tone and shock) to reveal the neural mechanisms of Pavlovian conditioning are also used in avoidance conditioning. The previously funded grant examined the contribution of the amygdala, a key structure for Pavlovian aversive conditioning, to avoidance. In the present proposal we continue to pursue the role of the amygdala, but in addition also attempt to begin to reveal the broader circuitry involved. Specifically, we examine the role of connections between the subareas of the amygdala and accumbens, in the transition from Pavlovian conditioned reactions to negatively reinforced avoidant actions.

 描述（由适用提供）：尽管有大量工作，但成瘾的神经元基础仍然仅部分理解。近年来，在理解药物作为积极的激励和奖励方面取得了很多进展。尽管人们一直知道厌恶动机在成瘾中也发挥了作用，但这是不太清楚的。与环境压力或戒断药物相关的外部刺激是负面的增强，通过加强行为，从而导致逃避和/或避免这些Stimulli引起的厌恶状态的行为，从而导致工具性药物寻求和消费反应。由于主动回避条件是基于负面的强化，并涉及与成瘾重叠的大脑回路，因此我们认为对逃生/回避行为的神经基础的详细理解将提供重要的信息，从而可以更深入地了解厌恶状态在药物滥用中的作用。尽管在1950年代和60年代对避免的神经元基础上进行了许多研究，但这项工作不受欢迎，部分原因是结果并未导致对电路的清晰了解。然而， 在随后的几年中，详细阐明了回避第一阶段的神经元基础，即帕夫洛维亚的恐惧调节。这些信息使得以新的眼光重新审视避免的神经元基础。特别是，鉴于我们现在详细了解 Neural mechanisms through which a neutral environmental stimulus associated with an aversive unconditioned stimulus (US) becomes a Pavlovian conditioned stimulus (CS) that elicits aversive states, we can now build on this information to understand the neuronal basis of avoidance conditioning, especially if the same stimulli used as CSs and USs (tone and shock) to reveal the neuronal mechanisms of Pavlovian conditioning are also used在回避条件下。先前资助的赠款研究了杏仁核（杏仁核）的贡献，杏仁核（巴夫洛夫厌恶条件的关键结构）避免了。在本提案中，我们继续攻读杏仁核的作用，但此外，还试图开始揭示涉及的更广泛的电路。具体而言，我们研究了杏仁核和Acumbens的亚地区之间的联系，在从帕夫洛夫条件反应到负强化的避免行动的过渡中。