Establishing a link between habits and punishment resistance

在习惯和惩罚抵抗之间建立联系

• 批准号: 10319496
• 负责人: RACHEL J SMITH
• 金额: $ 34.8万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10319496
• 关键词: Adopted; Affect; Animal Model; Area; Automobile Driving; Autopsy; Behavior; Behavioral; Brain; Characteristics; Cocaine; Corpus striatum structure; Data; Development; Dorsal; Drug usage; Exertion; FOS gene; Failure; Functional disorder; Goals; Habits; Individual; Intravenous; Label; Lead; Learning; Lesion; Link; Mediating; Methodology; Methods; Modeling; N-Methylaspartate; Nature; Neurons; Outcome; Pathway interactions; Pharmaceutical Preparations; Play; Prefrontal Cortex; Procedures; Process; Psychological reinforcement; Punishment; Rattus; Reinforcement Schedule; Resistance; Role; Self Administration; System; Testing; Thalamic structure; Training; Work; addiction; base; cocaine self-administration; drug seeking behavior; experimental study; innovation; insight; maladaptive behavior; neural network; neurobiological mechanism; novel; optogenetics; recruit; relating to nervous system; response; stem; tool; treatment strategy

PROJECT SUMMARY The defining characteristic of addiction is an uncontrollable urge to use drugs despite negative conse- quences (i.e., punishment). Addicted individuals find it difficult to curb drug-seeking behaviors even when they lead to harmful consequences, indicating that these behaviors are resistant to punishment. A similar type of punishment resistance has been observed in recent animal models of addiction, with a subset of rats continuing to self-administer cocaine despite receiving footshock. A prevailing view in the field is that punishment resistance arises from failure to exert goal-directed control over habits. However, a major gap in this account is that there is a lack of empirical evidence to support it. While goal-directed and habitual behaviors are known to be mediated by separate neural systems in dorsomedial striatum and dorsolateral striatum, respectively, much less is known about how punishment affects well-established behavior guided by these systems. Without a clear understanding of what drives punishment resistance in addiction, development of successful treatment strategies will continue to be hindered. The overall objective of this project is to establish a link between habitual responding and pun- ishment resistance in a rat self-administration model. The central hypothesis is that punishment resistance stems from a failure to switch from habitual responding to goal-directed control, due to reduced recruitment of cortical and thalamic inputs to dorsomedial striatum. The specific aims of this project are to: determine the role of habitual responding in punishment resistance, identify striatal components involved in punishment resistance and sensi- tivity, and identify inputs to striatum that mediate the response to punishment. These aims will be investigated using a systems-level approach that involves translationally-relevant animal models of addiction, optogenetic tools, and a novel outcome devaluation procedure that was developed to assess habitual responding for cocaine. These studies will provide critical new evidence for the theoretical framework commonly used by the field, and provide key insights into the behavioral processes and neurobiological mechanisms of compulsive drug use despite negative consequences.

项目概要 成瘾的本质特征是尽管会产生负面影响，但仍无法控制地使用毒品的冲动。 序列（即惩罚）。成瘾者发现很难抑制寻求毒品的行为，即使他们 导致有害后果，表明这些行为是对惩罚的抵抗力。类似类型的 在最近的成瘾动物模型中观察到惩罚抵抗，其中一部分老鼠继续 尽管受到足部电击，仍自行服用可卡因。该领域的一个普遍观点是，惩罚抵抗 源于未能对习惯进行目标导向的控制。然而，这个帐户的一个主要差距是， 是缺乏经验证据支持。虽然已知目标导向的习惯性行为是可以调节的 分别由背内侧纹状体和背外侧纹状体中的独立神经系统组成，目前所知甚少 关于惩罚如何影响这些系统指导下的既定行为。没有清晰的认识 关于成瘾行为中惩罚抵抗的驱动力，将继续制定成功的治疗策略 受到阻碍。该项目的总体目标是在习惯性反应和双关语之间建立联系 大鼠自我给药模型中的免疫耐受。中心假设是惩罚抵抗源于 由于皮层招募减少，无法从习惯性反应转变为目标导向控制 丘脑对背内侧纹状体的输入。该项目的具体目标是： 确定习惯的作用 响应惩罚抵抗，识别参与惩罚抵抗和敏感的纹状体成分 活性，并确定纹状体的输入，以调节对惩罚的反应。这些目标将受到调查 使用系统级方法，涉及成瘾的翻译相关动物模型、光遗传学 工具，以及一种新颖的结果贬值程序，该程序是为评估可卡因的习惯反应而开发的。 这些研究将为该领域常用的理论框架提供重要的新证据，并且 提供对强迫性药物使用的行为过程和神经生物学机制的关键见解 尽管产生了负面后果。