权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Alcohol and inhibition in the prefrontal cortex

酒精和前额皮质的抑制

基本信息

批准号：
8549688
负责人：
Michael Charles Salling
金额：
$ 5.22万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-30 至 2014-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8549688
关键词：
Acute Adolescence Adolescent Adult Affect Age Alcohol abuse Alcohol consumption Alcohols American Animal Model Animals Area Attention Awareness Behavior Behavior Control Behavioral Brain Brain region Chronic Complement Control Groups Data Decision Making Dependence Depressed mood Development Disease Dose Electrophysiology (science)Epidemiology Frequencies Functional disorder Funding GABA Antagonists GABA Receptor GABA-A Receptor Glycine Glycine Receptors Goals Healthcare Individual Lead Life Maintenance Measures Mediating Medicine Membrane Memory Mus Neuraxis Neurons Neurotransmitter Receptor Neurotransmitters Output Pathology Personal Satisfaction Pharmaceutical Preparations Physiological Physiological Adaptation Prefrontal Cortex Productivity Property Protocols documentation Public Health Relapse Research Research Proposals Rodent Slice Societies Substance abuse problem Synapses System Testing Thalamic structure Therapeutic Training Whole-Cell Recordings Work addiction alcohol effect alcohol exposure alcohol research alcohol response alcohol sensitivity alcohol use disorder binge drinking brain cell chronic alcohol ingestion cost critical period dentate gyrus design drinking family structure gamma-Aminobutyric Acid hippocampal pyramidal neuron inhibitor/antagonist neurobiological mechanism neuronal excitability neurotransmission novel postnatal prevent receptor research study substance abuser therapeutic development transmission process underage drinking voltage clamp

项目摘要

DESCRIPTION (provided by applicant): The consequences of alcohol abuse on the American public are profound, both in terms of individual well-being and impact on the family structure, as well as the enormous cost to society in terms of lost productivity and associated health care expenses. Despite increasing efforts, our understanding of the neurobiological mechanisms that underlie the effects of alcohol and the development of alcohol use disorders remains incomplete. Epidemiological research has pointed to adolescence as a critical period in the development of alcohol disorders. One area of the brain that appears especially vulnerable to the effects of alcohol is the prefrontal cortex (PFC), which remains immature at the onset of adolescence. The PFC is involved in decision- making, memory and impulse control, behaviors that are often disrupted following consumption of alcohol and are believed to underlie long-term addiction. In the PFC, pharmacologically relevant doses of alcohol are known to depress neuronal activity (Tu et al. 2007), but very little is known of its interactions with the inhibitor receptors, GABA and glycine, within the PFC. This is despite the expression of GABA-A receptor subtypes in the PFC (Hoestgaard-Jensen et al. 2010) that mediate tonic inhibition in other brain regions and demonstrate high sensitivity to alcohol (Wei et al. 2004, Jia et al. 2008). In addition, we note that functional glycine receptors are also present in PFC (Ye et al. 2011) but have received little to no attention. The goal of this research proposal is to examine the pharmacological actions of alcohol on neuronal excitability and on GABA and glycine-mediated synaptic and tonic inhibition in the adolescent PFC, and to determine if chronic alcohol drinking during adolescence leads to specific alterations of inhibition that affect neuronal excitability. Tis information could enhance our understanding of the negative effects of alcohol drinking during adolescence and an increased focus on cellular mechanisms involved can help lead to the development of therapeutic strategies to treat alcohol use disorders.

描述（由申请人提供）：酗酒对美国公众的影响是深远的，无论是在个人福祉和对家庭结构的影响方面，还是在生产力损失和相关医疗费用方面对社会造成的巨大成本方面。尽管越来越多的努力，我们对酒精影响和酒精使用障碍发展的神经生物学机制的理解仍然不完整。流行病学研究指出，青春期是酒精障碍发展的关键时期。大脑中有一个区域似乎特别容易受到酒精的影响，那就是前额叶皮层（PFC），它在青春期开始时还不成熟。PFC参与决策、记忆和冲动控制，这些行为通常在饮酒后被打乱，被认为是长期成瘾的基础。在PFC中，已知药药学上相关剂量的酒精会抑制神经元活动（Tu et al. 2007），但对其与PFC内GABA和甘氨酸抑制剂受体的相互作用知之甚少。尽管在PFC中表达GABA- a受体亚型（Hoestgaard-Jensen et al. 2010），介导大脑其他区域的强直性抑制，并表现出对酒精的高敏感性（Wei et al. 2004, Jia et al. 2008）。