Adolescent Alcohol and Prefrontal Cortical Function in the Adult

青少年酒精与成人前额皮质功能

基本信息

批准号：
9756243
负责人：
L Judson Chandler
金额：
$ 33.64万
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 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9756243
关键词：
Acute Address Adolescence Adolescent Adult Adverse effects Agonist Alcohol consumption Alcohols Area Behavior Behavior Control Behavior assessment Behavioral Brain Cell Nucleus Clinical Cognitive deficits Consumption Data Decision Making Development Drug effect disorder Electrophysiology (science)Ethanol Exhibits Functional disorder Funding Future Goals Histone Deacetylase Inhibitor Illicit Drugs Impairment In Vitro Intoxication Knowledge Legal Measures Mediating Methodology Midbrain structure Morphology National Institute on Alcohol Abuse and Alcoholism Neurons Neurotransmitters Neurotrophic Tyrosine Kinase Receptor Type 2 Pathway interactions Pattern Pharmaceutical Preparations Pharmacogenetics Pharmacology Prefrontal Cortex Procedures Process Property Public Health Rattus Regulation Research Resistance Rewards Risk-Taking Safety Short-Term Memory Signal Transduction Slice Stains Structure System Testing Time Vertebral column adolescent alcohol abuse adolescent alcohol effect adolescent alcohol exposure age group alcohol exposure alcohol seeking behavior behavior measurement brain behavior cognitive enhancement cognitive function critical period drinking drug of abuse executive function experimental study flexibility frontal lobe innovation interest multidisciplinary neuropathology novel novel strategies novel therapeutic intervention optogenetics positive allosteric modulator pre-clinical public health relevance receptor 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 high levels of intoxication. In addition to legal ramifications and concerns with physical safety, these patterns of alcohol consumption appear to adversely impact continued brain and behavioral maturation 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. 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. Consistent with this, we have demonstrated that adolescent intermittent ethanol (AIE) exposure results in behavioral deficits in adulthood. Specifically, thes studies reveal that AIE-exposed adult rats exhibit inflexible decision-making that is consistent with prefrontal dysfunction. The studies under this renewal component of the NADIA consortium will build upon these observations through the following four specific aims: 1) Test the hypothesis that AIE-induced deficits in behavioral flexibility in adulthood are associated with circuit-specific alterations of PFC projections to subcortical structures. 2) Test the hypothesis that prelimbic PFC inputs to the RMTg mediate AIE-induced reduction in adult sensitivity to the aversive actions of ethanol. 3) Test the hypothesis that AIE facilitates the development of inflexible habitual ethanol seeking through disruption of PFC-mediated control of response strategy selection. 4) Test the hypothesis that pharmacologic and pharmacogenetic enhancement of cognitive function can restore behavioral flexibility in the AIE-exposed adult. These studies involve an innovative and multidisciplinary set of experiments that utilize state-of-the-art methodologies and procedures. Together, these studies will yield novel and exciting new findings and will significantly advance our understanding of the effect of adolescent alcohol exposure on cognitive function and behavioral control in the adult, and identify novel therapeutic approaches for treatment.

描述（通过应用程序提供）：青少年和成年时期酒精的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中大量食用酒精，从而导致高水平的中毒。除了对身体安全的法律影响和关注，这些饮酒模式在从青少年到成年期的过渡期间似乎对持续的大脑和行为成熟产生了不利影响。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）。青少年代表了支持执行认知功能成熟的PFC神经记录的关键时期。 NADIA联盟的这一研究成分的总体假设是，在青春期生产过程中，反复的暴饮暴食暴露于饮酒中，PFC的神经病理学在成年人中表现为执行认知功能和行为控制中定义的。与此一致，我们已经证明了青少年间歇性乙醇（AIE）的暴露会导致成年后的行为定义。具体而言，研究表明，暴露于AIE的成年大鼠表现出僵化的决策，这与前额叶功能障碍一致。 NADIA财团的这种更新成分下的研究将通过以下四个特定目的基于这些观察结果：1）检验以下假设：成年后AIE诱导的行为灵活性缺陷与PFC项目的电路特异性变化有关，对皮层结构的电路特异性改变。 2）检验以下假设：RMTG的前PFC输入介导了AIE诱导的成人敏感性对乙醇的厌恶作用的降低。 3）检验了AIE伴侣通过破坏PFC介导的对响应策略选择的控制而发展的假设，即AIE伴侣发展了不灵活的习惯性乙醇寻求。 4）检验以下假设：认知功能的药理和药物遗传学增强可以恢复AIE暴露的成年人的行为灵活性。这些研究涉及使用最新方法和程序的创新和多学科实验集。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成年人对青少年酒精暴露对认知功能和行为控制的影响的理解，并确定新颖的治疗方法的治疗方法。