CNS Effects of Alcohol: Cellular Neurobiology

酒精对中枢神经系统的影响：细胞神经生物学

• 批准号: 7617205
• 负责人: George F. Koob
• 金额: $ 182.47万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7617205
• 关键词: ARHGEF5 gene; Abstinence; Accounting; Acute; Address; Adolescence; Adolescent; Adult; Affect; Age; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholism; Alcohols; Amygdaloid structure; Animal Model; Animals; Automobile Driving; Award; Basic Science; Behavior; Behavioral; Biochemical; Boutos; Brain; Cellular Neurobiology; Chronic; Clinical; Communication; Communities; Corticotropin-Releasing Hormone; Dependence; Development; Diagnosis; Dopamine; Drunk driving; Education; Elements; Endocannabinoids; Epidemiologic Studies; Ethanol; Ethanol dependence; Faculty; Funding; Genetic; Genotype; Glutamates; Grant; Heavy Drinking; Hormonal; Human; Hypothalamic structure; Individual; Information Dissemination; Interdisciplinary Study; Intoxication; Lead; Life; Measures; Mentored Research Scientist Development Award; Methods; Mexican Americans; Minority; Modeling; Molecular; Motivation; National Institute on Alcohol Abuse and Alcoholism; Negative Reinforcements; Neuraxis; Neurobiology; Neuroendocrinology; Neuromodulator; Neuropeptides; Neuropharmacology; Neurotransmitters; Nucleus Accumbens; Opioid Peptide; Pharmaceutical Preparations; Phenotype; Pilot Projects; Pituitary Gland; Play; Population; Predisposition; Prevalence; Probability; Procedures; Process; Rattus; Recruitment Activity; Relative (related person); Research; Research Institute; Research Personnel; Residual state; Rewards; Role; Self Administration; Self-Administered; Serotonin; Solutions; Source; Staging; Stress; Structure of terminal stria nuclei of preoptic region; Synapses; System; Testing; Time; Training; Translating; Ventral Tegmental Area; Withdrawal; Work; addiction; adolescent alcohol; adolescent alcohol exposure; alcohol effect; alcohol exposure; alcohol reinforcement; alcohol research; animal model development; basal forebrain; base; binge drinking; clinical phenotype; daily functioning; drinking; gamma-Aminobutyric Acid; insight; member; neural circuit; neuroadaptation; neurobehavioral; neurobiological mechanism; neurochemistry; neuropeptide Y; neuropsychological; neurosteroids; novel; outreach; prevent; programs; response; reward circuitry; young adult

DESCRIPTION (Provided by applicant): The Alcohol Research Center of The Scripps Research Institute (TSRI-ARC) proposes to continue its interdisciplinary program focused on the theme of the central nervous system effects of alcohol. For this renewal application, the TSRI-ARC will be a P60 consisting of 9 components plus an Educational Component. Four core components are proposed: Administrative, Animal Models Development, Biochemical and Pilot. Five research components are proposed: Cellular Neurobiology (Roberto/Siggins), Neuroendocrinology (Rivier), Neuropharmacology Neuropeptides (Zorrilla/Weiss), Neuropharmacology Endocannabinoids (Parsons), and Clinical Neurobehavioral (Ehlers). The overall hypothesis of the TSRIARC is that the function of specific neurotransmitter synapses in select parts of the reward and stress systems that are compromised by chronic ethanol administration account for the development of vulnerability to alcoholism in genetically prone individuals. Two major themes have emerged from our present research 1) the neuropharmacological mechanisms of vulnerability to dependence depend on how specific brain reward and stress circuits change during the transition from initiation of drinking to binge drinking to dependence (Specific Aims 1 &2); 2) the neuropharmacological changes produced by binge drinking in adolescents and young adults may drive excessive drinking and vulnerability to dependence in adults (Specific Aim 3). Progress during the previous funding period has led to a focus on understanding dependence-induced neuroadaptive mechanisms and residual allostatic changes that persist following acute abstinence. The new focus of the ARC is on neuroadaptive changes that are engaged by binge drinking that form a transition from initiation of drinking to dependence and form a crucial part of the basis for inheritable susceptibility to human alcoholism. The TSRI-ARC also supports the Center at Large, which includes: seventeen NIAAA R01's, two U01's, four NIAAA R21's, two NIAAA R37 awards, one NIAAA T32 training grant, one NIAAA K01 award and one NIAAA K99 award. Training and information dissemination to the San Diego community will be effected by the training opportunities of the Center including an NIAAA training grant and the Education Component.

描述（由申请人提供）：斯克里普斯研究所酒精研究中心（TSRI-ARC）提议继续其跨学科项目，重点关注酒精对中枢神经系统影响的主题。对于此更新应用程序，TSRI-ARC 将是由 9 个组件和一个教育组件组成的 P60。提出了四个核心组成部分：行政、动物模型开发、生化和试点。提出了五个研究内容：细胞神经生物学（Roberto/Siggins）、神经内分泌学（Rivier）、神经药理学神经肽（Zorrilla/Weiss）、神经药理学内源性大麻素（Parsons）和临床神经行为学（Ehlers）。 TSRIARC 的总体假设是，奖励和压力系统的特定部分的特定神经递质突触的功能受到长期乙醇注射的损害，导致了遗传倾向个体容易酗酒。我们目前的研究出现了两个主要主题：1）易产生依赖的神经药理学机制取决于从开始饮酒到酗酒再到依赖的过渡过程中特定的大脑奖赏和压力回路如何变化（具体目标1和2）； 2) 青少年和年轻人酗酒所产生的神经药理学变化可能会导致成人过度饮酒并容易产生依赖性（具体目标 3）。上一个资助期间取得的进展使人们关注于了解依赖引起的神经适应机制以及急性戒断后持续存在的残余变稳态变化。 ARC 的新焦点是酗酒引起的神经适应性变化，这些变化形成从饮酒开始到依赖的转变，并构成人类酗酒遗传易感性基础的重要组成部分。 TSRI-ARC 还支持大型中心，其中包括：17 个 NIAAA R01、2 个 U01、4 个 NIAAA R21、2 个 NIAAA R37 奖项、1 个 NIAAA T32 培训补助金、1 个 NIAAA K01 奖项和 1 个 NIAAA K99 奖项。圣地亚哥社区的培训和信息传播将受到该中心的培训机会的影响，包括 NIAAA 培训补助金和教育部分。