Establishing a link between habits and punishment resistance

项目总结 上瘾的决定性特征是一种无法控制的吸毒冲动，尽管有负面影响-- 惩罚(即惩罚)。吸毒成瘾的人发现很难遏制寻找毒品的行为，即使当他们 导致有害后果，说明这些行为是抗拒惩罚的。一种类似类型的 在最近的成瘾动物模型中观察到了惩罚抵抗，部分大鼠仍在继续 尽管受到脚部电击，但仍自行注射可卡因。该领域的一种流行观点是惩罚抵抗 起因于未能对习惯实施目标导向控制。然而，这个账户中的一个主要缺口是， 是缺乏经验证据来支持这一观点。虽然目标导向和习惯性行为被认为是中介的 通过分别在背内侧纹状体和背外侧纹状体中分离神经系统，我们所知的要少得多。 关于惩罚如何影响由这些系统指导的既定行为。没有明确的认识 对于是什么驱使成瘾患者抵制惩罚，成功的治疗策略的开发将继续下去 被阻挠。这个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递质抵抗。中心假设是惩罚抵抗源于 从未能从习惯性反应转向目标导向控制，这是由于皮质招募减少所致 丘脑传入背内侧纹状体。这个项目的具体目标是：确定习惯性的作用 惩罚抵抗反应，识别参与惩罚抵抗和感觉的纹状体成分 活动，并确定纹状体的输入，调节对惩罚的反应。将对这些目标进行调查 使用一种系统水平的方法，包括翻译相关的成瘾动物模型，光遗传学 工具，以及为评估对可卡因的习惯性反应而开发的一种新的结果贬值程序。 这些研究将为实地普遍使用的理论框架提供关键的新证据，以及 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 尽管有负面后果。

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.