Neural systems mediating the extinction and inhibition of cocaine seeking

介导可卡因寻求的灭绝和抑制的神经系统

基本信息

批准号：
10610379
负责人：
RYAN T LALUMIERE
金额：
$ 44.29万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-15 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10610379
关键词：
Amygdaloid structure Behavior Behavioral Brain region Cell Nucleus Cocaine Cocaine Dependence Consumption Custom Data Development Drug usage Elements Etiology Extinction Face Failure Frequencies Future Goals Heterogeneity Hippocampus Human Impairment Implant Individual Knowledge Laboratories Medial Mediating Modeling Neural Pathways Neurons Neurosciences Nucleus Accumbens Output Pathway Analysis Pathway interactions Pharmaceutical Preparations Play Prefrontal Cortex Process Rattus Relapse Research Rodent Role Site Structure Structure of paraventricular nucleus of thalamus System Testing Thalamic structure Training Work cocaine relapse cocaine seeking cocaine self-administration cocaine use craving design effective therapy experimental study insight learning extinction multi-electrode arrays neural neural circuit novel strategies optogenetics public health relevance

项目摘要

Relapse to cocaine use remains a significant challenge in the treatment of cocaine addiction, yet our understanding of those neural systems that enable individuals to inhibit cocaine seeking and relapse remains poor. The long-term goal of our laboratory is to identify the neural circuits and the changes in those circuits that underlie the inhibition of cocaine-seeking behavior, using rat models of cocaine seeking. The current proposal builds upon the findings we have obtained in recent years as well as new approaches we have developed in our laboratory. In our studies, rats undergo cocaine self-administration, extinction training and reinstatement testing of their cocaine seeking. We have found that the infralimbic cortex is a central component of the systems involved in the extinction and inhibition of cocaine-seeking behavior. Activity in the infralimbic cortex is necessary for the normal encoding of the extinction learning as well as extinction expression. For example, infralimbic activation inhibits cocaine seeking following extinction training. However, the larger circuit in which the infralimbic cortex performs these functions remains unclear. In particular, as evidence suggests functional heterogeneity within the infralimbic cortex in terms of its role in cocaine seeking, understanding the larger circuitry may provide insight into these issues. The proposed work will focus on the specific pathways projecting into and out of the infralimbic that account for its role in extinction and inhibition of cocaine seeking. The work will include approaches that have not, to our knowledge, been used in studies of cocaine seeking and, therefore, will enable notable progress in our knowledge of these systems. In particular, our studies will use multi-site recordings of neural activity during cocaine seeking to understand how a network of brain regions coordinates behavior. Moreover, the proposed studies will use optogenetic approaches to examine how different pathways mediate different aspects of the extinction and inhibition of cocaine seeking. The findings from this work will reveal those specific pathways and network activity related to the IL with regard to the extinction/inhibition of cocaine seeking. Furthermore, the proposed work will both 1) examine changes in IL-based circuits as a consequence of cocaine self-administration and extinction and 2) manipulate these circuits to determine how they functionally control the inhibition of cocaine seeking. The findings from the studies will furnish critical new basic knowledge of the neural systems underlying the suppression of cocaine seeking that will potentially lead to the development of more effective treatments that strengthen such systems in cocaine-addicted individuals.

可卡因吸毒复发仍然是治疗可卡因成瘾的一个重大挑战，但我们对那些使个人能够抑制可卡因寻求和复吸的神经系统的理解仍然存在贫穷的。我们实验室的长期目标是识别神经回路以及这些回路的变化使用大鼠可卡因寻求模型来抑制可卡因寻求行为。目前的提案建立在我们近年来获得的发现以及我们开发的新方法的基础上我们的实验室。在我们的研究中，大鼠接受可卡因自我给药、灭绝训练和恢复测试他们对可卡因的寻求。我们发现边缘下皮层是大脑的核心组成部分参与消除和抑制可卡因寻求行为的系统。边缘下皮层的活动是对于消退学习和消退表达的正常编码是必需的。例如，边缘下激活抑制了消退训练后对可卡因的寻求。然而，较大的电路边缘下皮层执行这些功能的情况仍不清楚。特别是，有证据表明功能性边缘下皮质内的异质性就其在可卡因寻求、理解更大的作用方面的作用而言电路可以提供对这些问题的深入了解。拟议的工作将侧重于具体途径投射到下边缘系统中和之外，这解释了其在消除和抑制可卡因寻求方面的作用。据我们所知，这项工作将包括尚未用于可卡因寻求研究的方法因此，这将使我们对这些系统的了解取得显着进展。特别是，我们的研究将使用可卡因期间神经活动的多站点记录来寻求了解大脑网络如何区域协调行为。此外，拟议的研究将使用光遗传学方法来检查不同的途径如何介导可卡因寻求的消除和抑制的不同方面。这这项工作的结果将揭示与 IL 相关的那些特定途径和网络活动消除/抑制对可卡因的寻求。此外，拟议的工作将 1）检查基于 IL 的回路是可卡因自我施用和消除的结果，2) 操纵这些确定它们如何在功能上控制对可卡因寻求的抑制的电路。研究结果来自研究将为抑制可卡因的神经系统提供重要的新基础知识寻求这可能会导致开发出更有效的治疗方法来增强此类系统可卡因成瘾者。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Theta oscillations in rat infralimbic cortex are associated with the inhibition of cocaine seeking during extinction.

DOI：
10.1111/adb.13106
发表时间：
2022-01
期刊：
Addiction biology
影响因子：
3.4
作者：
Müller Ewald VA;Kim J;Farley SJ;Freeman JH;LaLumiere RT
通讯作者：
LaLumiere RT

Infralimbic Projections to the Nucleus Accumbens Shell and Amygdala Regulate the Encoding of Cocaine Extinction Learning.

下边缘对伏核壳和杏仁核的投射调节可卡因灭绝学习的编码。

DOI：
10.1523/jneurosci.2023-22.2022
发表时间：
2023
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Nett,KelleE;Zimbelman,AlexaR;McGregor,MatthewS;AlizoVera,Vanessa;Harris,MollyR;LaLumiere,RyanT
通讯作者：
LaLumiere,RyanT

Theoretical Considerations for Optimizing the Use of Optogenetics with Complex Behavior.

优化复杂行为光遗传学应用的理论考虑。