Long term consequences of adolescent alcohol use on behavioral inhibition

青少年饮酒对行为抑制的长期影响

基本信息

批准号：
10533163
负责人：
BITA MOGHADDAM
金额：
$ 22.14万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10533163
关键词：
Adolescence Adolescent Adolescent Development Adult Affect Alcohol consumption Alcohols Animal Model Animals Anxiety Disorders Association Learning Behavior Behavioral Behavioral Model Behavioral Paradigm Behavioral inhibition Brain Brain region Clinical Communication Computer Analysis Control Animal Corpus striatum structure Cues Data Development Dorsal Electrophysiology (science)Ethanol Event Exposure to Feeling suicidal Female Future Genetic Impairment Impulsivity Individual Knowledge Laboratories Lateral Lead Learning Link Literature Medial Mediating Mental Processes Modeling Mood Disorders Neurons Outcome Pathway interactions Protocols documentation Rattus Recording of previous events Research Rewards Risk Factors Rodent Role Signal Transduction Substance Use Disorder Sucrose Suicide attempt Task Performances Testing Water Work addiction adolescent alcohol exposure adverse outcome alcohol exposure alcohol use disorder behavior observation behavioral impairment clinically relevant cue reactivity design designer receptors exclusively activated by designer drugs drinking experience experimental study flexibility genetic approach genetic manipulation intervention effect male mature animal neural neural network novel receptor response underage drinking

项目摘要

PROJECT SUMMARY Adolescence is a “vulnerable” period because certain experiences in this period lead to detrimental lasting effects. A critical example is teenage drinking which may predispose them to life-long adverse consequences including impulsivity and impaired response inhibition. In this exploratory R21 application, we propose to exploit a rodent behavioral model to begin to understand the neuronal basis of the long-term consequences of voluntary adolescent drinking on response inhibition. Using a novel behavioral task, we find that moderate voluntary intake of alcohol during adolescence causes a robust reduction in response inhibition in both male and female adult rats. Guided by basic and clinical literature suggesting that orbitofrontal cortex (OFC) and dorsal striatum (DS) are critical for action-guided learning and impulsivity, we propose two exploratory aims to begin to understand the computational and circuit-based involvement of these two regions in mediating or modulating impaired response inhibition in adults with a history of adolescent alcohol drinking. In Aim 1, we will record from multiple units and local field potentials (LFPs) simultaneously in lateral OFC and medial DS during task performance to determine if neural encoding of relevant task events and OFC-DS coordinated activity is affected in correlation with behavioral changes. In Aim 2, we will use a chemogenetic approach to manipulate OFC-DS connections to determine the potential causative role of this pathway on the sustained impact of adolescent alcohol use on adult impulsivity. Regardless of the outcome, completion of this exploratory work will provide technical and mechanistic knowledge to support future more comprehensive studies on the neuronal basis of the lasting impact of adolescent alcohol use.

项目概要青春期是一个“脆弱”时期，因为这个时期的某些经历会导致持久的痛苦一个重要的例子是青少年饮酒，这可能会使他们遭受终生的不良后果。包括冲动和反应抑制受损。在这个探索性 R21 应用中，我们建议：利用啮齿动物行为模型来开始了解长期后果的神经基础通过一项新颖的行为任务，我们发现青少年自愿饮酒对抑制反应有一定的影响。青春期自愿饮酒会导致男性的反应抑制显着减少和雌性成年大鼠的基础和临床文献表明，眶额皮质（OFC）和背侧纹状体（DS）对于行动引导学习和冲动至关重要，我们提出了两个探索性目标开始了解这两个区域在调解或中的计算和基于电路的参与在目标 1 中，我们将调节有青少年饮酒史的成年人的反应抑制受损。在外侧 OFC 和内侧 DS 中同时记录多个单元和局部场电位 (LFP) 任务性能以确定相关任务事件和 OFC-DS 协调活动的神经编码是否在目标 2 中，我们将使用化学遗传学方法来操纵。 OFC-DS 连接以确定该途径对持续影响的潜在因果作用无论结果如何，这项探索性工作的完成都将影响青少年饮酒对成人冲动的影响。提供技术和机械知识以支持未来更全面的神经元研究青少年饮酒的持久影响的基础。