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Adolescent binge drinking and effects on adult brain and behavior: the importance of sex differences

青少年酗酒及其对成人大脑和行为的影响：性别差异的重要性

基本信息

批准号：
9081749
负责人：
Heather N. Richardson
金额：
$ 36.62万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9081749
关键词：
Abstinence Address Adolescence Adolescent Adolescent Development Adult Affect Age Alcohol abuse Alcohol consumption Alcohols Animal Model Axon Behavior Control Behavioral Biochemical Brain Injuries Cognitive Cognitive deficits Data Demyelinations Dependence Detection Development Dose Drug abuse Emotions Ensure Female Female Adolescents Fiber Functional disorder Genetic Predisposition to Disease Gonadal Hormones Grant Heavy Drinking Hormonal Hormones Human Image Imaging Techniques Individual Inflammation Injury Investigation Knowledge Lead Life Literature Male Adolescents Medial Memory impairment Mental Health Mental disorders Methods Modeling Molecular Myelin Nature Neurons Oligodendroglia Oxidative Stress Pathology Pattern Play Prefrontal Cortex Prevalence Process Production Rattus Relapse Research Resolution Risk Rodent Model Role Sex Characteristics Short-Term Memory Signal Transduction Speed Testing Testosterone Therapeutic Intervention Thick Time Transmission Electron Microscopy Woman Work addiction adolescent binge drinking alcohol effect alcohol exposure alcohol use disorder base binge drinking brain behavior combat density drinking drinking behavior early adolescence early alcohol use fluorescence imaging frontal lobe gender difference hormone deficiency insight knowledge base male myelination new therapeutic target novel postnatal pre-clinical protective effect public health relevance relating to nervous system remyelination repaired research study response sex therapeutic target underage drinking white matter

项目摘要

DESCRIPTION (provided by applicant): Early onset of alcohol use is associated with cognitive deficits and enhanced vulnerability to alcohol use disorder in adulthood. Individuals may be vulnerable to alcohol at this time because the frontal lobes are undergoing significant myelination throughout adolescence to enhance working memory and increase control of behaviors and emotions in adulthood. Myelination is a process in which oligodendrocytes wrap white fatty sheaths around axons of mature neurons to an optimal thickness that ensures high-speed propagation of electrical signals along an axon and enhances neural connectivity. Imaging studies suggest that heavy drinking may increase addiction risk and mental health vulnerability in adulthood by disrupting myelination during adolescent development. Alternatively, these relationships could be due to shared genetic predispositions rather than result from alcohol exposure. We have used a preclinical animal model of voluntary binge drinking to begin dissecting the causal nature of these relationships between alcohol and myelinated fiber tracks in the frontal lobes. Our findings indicate adolescent binge drinking induces prefrontal myelin loss and enhances drinking risk in adulthood. The current proposal combines powerful biochemical, neuroanatomical, and behavioral approaches to gain insight into how alcohol differentially affects prefrontal myeloarchitecture in males and females and empirically test the role of pubertal hormones in heightened vulnerability to alcohol during adolescent development. These studies should lead to a greater understanding of myelination and potentially reveal new therapeutic targets to combat alcohol use disorder.