Impact of Adolescent Alcohol Exposure on Prefrontal Cortical Function in the Adul

青少年酒精暴露对成人前额皮质功能的影响

基本信息

批准号：
8530113
负责人：
L Judson Chandler
金额：
$ 31.76万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-05 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8530113
关键词：
Address Adolescence Adolescent Adult Affect Alcohol abuse Alcohol consumption Alcohols Attention Behavior Behavior Control Behavioral Biological Neural Networks Brain Chronic Cognitive Consumption Decision Making Development Dopamine Dopamine D2 Receptor Dose Drug abuse Electrodes Electrophysiology (science)Emotions Epidemiology Epigenetic Process Equilibrium Ethanol Exhibits Exposure to Functional disorder Health Histone Acetylation Human Image Immunohistochemistry In Vitro Interneurons Intoxication Label Legal Life Measurement Medial Mediating Methodology Microdialysis Modeling Modification Morphology Neurobiology Neurons Pattern Performance Pharmaceutical Preparations Play Population Prefrontal Cortex Procedures Process Public Health Rattus Research Risk Risk Behaviors Risk-Taking Rodent Role Safety Short-Term Memory Slice Task Performances Testing Unsafe Sex Ventral Tegmental Area Vertebral column adolescent alcohol exposure age group alcohol exposure analog cognitive function critical period dopaminergic neuron drinking executive function experience extracellular flexibility hippocampal pyramidal neuron in vivo information processing innovation multidisciplinary neurochemistry neuropathology novel research study response underage drinking young adult

项目摘要

DESCRIPTION (provided by applicant): The consumption of alcohol during adolescence and young adulthood is a serious public health problem. In this age group, alcohol is often consumed in large quantities in repeated binge-like episodes that result in serve levels of intoxication. In addition to legal ramifications and concerns with physical safety, these patterns of alcohol consumption appear to adversely impact continued neuromaturation during the transition from adolescence to adulthood. The prefrontal cortex (PFC) controls higher-order cognitive functions such as working-memory, behavioral flexibility, and impulse control (collectively referred to as executive cognitive function). Adolescence represents a critical period of refinement of the neurocircuitry of the PFC that supports maturation of executive cognitive functioning. Deficits in executive cognitive function are associated with loss of control over behavioral processes such as attention and emotion, and with increased engagement in risky behaviors such as unprotected sex and drug-taking. The latter includes a reduced ability to discontinue drug-taking once initiated resulting in escalation in, and loss of control over, consumption. The overarching hypothesis of this research component of the NADIA consortium is that repeated binge-like exposure to alcohol during adolescence produces a neuropathology of the PFC that manifests in the adult as deficits in executive cognitive function and behavioral control. This hypothesis will be tested by an innovative and multidisciplinary set of experiments that utilize state-of the- art methodologies and procedures in a rat model of adolescent intermittent ethanol (AIE) exposure. The overarching hypothesis will be tested by four specific aims that will: 1) Determine the effects of AIE exposure on epigenetic modifications (histone acetylation) in identified populations of excitatory pyramidal and inhibitory interneurons in the medial PFC and dopamine (DA) projection neurons in the ventral tegmental area; 2) Determine the effects of AIE exposure upon DA modulation of excitatory pyramidal and inhibitory GABAergic interneurons in the adult medial PFC; 3) Determine the effects of AIE exposure and re-exposure to alcohol during adulthood on executive cognitive function using tasks that assess working memory, behavioral flexibility, and risk-taking behavior; and 4) Assess the effects of AIE exposure and reexposure to alcohol during adulthood on cognitively modulated synchronous activity and organization of neuronal ensembles in the mPFC. Together, these studies will yield novel and exciting new finding and will significantly advance our understanding of the effect of adolescent alcohol exposure on cognitive function and behavioral control in the adult.

描述（由申请人提供）：青春期和成年期间的酒精消费是一个严重的公共卫生问题。在这个年龄段，通常会在重复的暴饮暴食发作中大量食用酒精，从而导致中毒水平。除了对物理安全的法律影响和关注点外，这些饮酒方式似乎对从青春期到成年期过渡期间的神经饱和持续不利。前额叶皮层（PFC）控制高阶认知功能，例如工作记忆，行为灵活性和脉冲控制（统称为执行认知功能）。青春期代表了支持执行认知功能成熟的PFC神经记录的关键时期。执行认知功能的缺陷与失去对行为过程（如注意力和情感的行为过程）的控制以及对危险行为（如无保护性和吸毒之类的危险行为）的参与有关。后者包括一旦开始启动毒品的能力降低，导致升级和失去控制能力。 NADIA联盟的这一研究成分的总体假设是，青春期中反复的暴饮暴食暴露在青春期中会产生PFC的神经病理学，该神经病理在成年人中表现为执行认知功能和行为控制的缺陷。该假设将通过一组创新和多学科的实验集来检验，这些实验将在青少年间歇性乙醇（AIE）暴露的大鼠模型中利用最新的方法和程序进行检验。总体假设将通过四个特定目的来测试：1）确定AIE暴露对表观遗传学修饰（组蛋白乙酰化）的影响，对兴奋性金字塔和抑制性抑制性抑制性元中的刺激型PFC和多巴胺（DA）抑制性神经元的抑制性群体（DA）的抑制性神经元（DA）在肠门夹角区域中的神经元（DA）; 2）确定AIE暴露对成人内侧PFC兴奋性锥体和抑制性GABA能中间神经元调节的影响； 3）使用评估工作记忆，行为灵活性和冒险行为的任务，确定AIE暴露和对酒精重新暴露对执行认知功能的影响； 4）评估AIE在成年期间暴露和重新暴露酒精对MPFC中认知调制的同步活动和神经元集合的组织的影响。这些研究将共同产生新颖而令人兴奋的新发现，并会大大提高我们对青少年酒精暴露对成人认知功能和行为控制的影响的理解。