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（由申请人提供）：尽管有大量的工作，成瘾的神经基础仍然只是部分理解。近年来，在理解药物作为积极激励和奖励的激励作用方面取得了很大进展。虽然人们早就知道厌恶性动机在成瘾中也起着一定的作用，但这一点还不太清楚。与环境压力或药物戒断相关的外部刺激是负强化，其通过强化允许逃离和/或避免由这些刺激引起的厌恶状态的行为来促进工具性药物寻求和消费反应。由于主动回避条件反射是基于负强化，并涉及与成瘾重叠的大脑回路，我们认为，逃避/回避行为的神经基础的详细了解将提供重要的信息，可以让更深入地了解厌恶状态在物质滥用中的作用。虽然在20世纪50年代和60年代进行了大量关于回避的神经基础的研究，但这项工作并不受欢迎，部分原因是结果并没有导致对电路的清晰理解。然而，在这方面， 在此期间，回避的第一阶段的神经基础，巴甫洛夫恐惧条件反射，已被详细阐明。这些信息使得我们有可能以新的视角重新审视回避的神经基础。特别是，鉴于我们现在详细了解了 神经机制，通过该神经机制，与厌恶性无条件刺激（US）相关联的中性环境刺激成为消除厌恶性状态的巴甫洛夫条件刺激（CS），我们现在可以基于这些信息来理解回避条件反射的神经基础，特别是当使用相同的刺激作为CS和US时（音调和电击）揭示巴甫洛夫条件反射的神经机制也被用于回避条件反射。先前资助的赠款检查了杏仁核的贡献，这是巴甫洛夫厌恶条件反射的关键结构，以避免。在目前的建议中，我们继续追求杏仁核的作用，但除此之外，也试图开始揭示更广泛的电路参与。具体来说，我们研究的作用，杏仁核和杏仁核的分区之间的连接，在巴甫洛夫条件反应的过渡到消极的强化回避行动。