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(由申请者提供)：尽管有大量的工作，但成瘾的神经基础仍然只有部分了解。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。尽管很早就知道厌恶动机在成瘾中也起到了作用，但人们对这一点的理解还不是很清楚。与环境应激或戒毒相关的外部刺激是通过加强行为来逃避和/或避免这些刺激引起的厌恶状态，从而促进工具性药物寻求和消费反应的负性强化。由于主动回避条件作用建立在负强化的基础上，并涉及与成瘾重叠的大脑回路，我们认为，详细了解逃避/回避行为的神经基础将提供重要信息，可能有助于更深入地理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年代进行了许多关于回避的神经基础的研究，但这项工作失去了人们的支持，部分原因是结果没有导致对电路的清晰理解。然而， 在这中间的几年里，第一阶段回避的神经基础，巴甫洛夫恐惧条件反射，已经被详细阐明。这些信息使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 通过中性环境刺激与厌恶的无条件刺激(US)相关的神经机制，我们现在可以建立在这些信息的基础上来理解回避条件反射的神经基础，特别是如果用于揭示巴甫洛夫条件刺激的神经机制的相同刺激也用于回避条件反射的话。之前的资助研究了杏仁核对回避的贡献，杏仁核是巴甫洛夫厌恶条件反射的关键结构。在目前的提案中，我们继续研究杏仁核的作用，但也试图开始揭示涉及的更广泛的回路。具体地说，我们研究了杏仁核和伏隔核亚区之间的联系在从巴甫洛夫条件性反应到负面强化的回避性反应的转变中所起的作用。