INIA: System Mechanisms in Stress-Alcohol Interactions

INIA：压力-酒精相互作用的系统机制

• 批准号: 7674444
• 负责人: DOUGLAS B MATTHEWS
• 金额: $ 15.74万
• 依托单位: BAYLOR UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7674444
• 关键词: GABA receptor; NMDA receptors; alcoholic beverage consumption; alcoholism /alcohol abuse; anxiety; behavior test; behavioral /social science research tag; behavioral genetics; cooperative study; dissection; gene expression; gene targeting; genetic models; genetic susceptibility; genetically modified animals; genotype; laboratory mouse; learning; neurobiology; neurochemistry; neurophysiology; protein structure function; self medication; serotonin receptor; stress

DESCRIPTION (provided by applicant): The neurobiological mechanisms that underlie the transition from controlled to uncontrolled, or excessive, drinking are not completely understood. Excessive drinking has been demonstrated following several different ethanol exposure paradigms in monkeys, rats and mice. Furthermore, the initiation and maintenance of ethanol self-administration involves several brain regions including the nucleus accumbens, amygdala and hippocampus. In addition, specific neurotransmitter receptor subtypes and/or transporters within these brain regions have been implicated in excessive ethanol self-administration. Recently, it has been demonstrated that acute stress administration can result in high levels of ethanol self-administration and reinstatement of ethanol self-administration in drug free animals. However, it is currently unknown if the initiation of excessive drinking is influenced by interactions between stress, specific brain regions, and specific genes. The current proposal will 1) investigate the neurobiological relationship between stress, anxiety and excessive drinking in knockout mice; 2) investigate the neurobiological relationship between chronic ethanol administration, stress and ethanol self-administration in knockout mice; and 3) identify significant neurobiological abnormalities in the relationship between stress and acute ethanol administration in knockout mice. These studies will fill a major gap in understanding the relationship between stress, brain regions, genetics and the development of excessive drinking.

描述（由申请人提供）： 从受控到的过渡为基础的神经生物学机制 尚不完全了解不受控制的或过多的饮酒。过多的 几次不同的乙醇暴露后已证明饮酒 猴子，大鼠和小鼠的范式。此外，启动和 维持乙醇自我给药涉及多个大脑区域 包括伏隔核，杏仁核和海马。此外， 特定的神经递质受体亚型和/或转运蛋白 大脑区域已与过度乙醇自我给药有关。 最近，已经证明可以导致急性应力给药 在高水平的乙醇自我给药和恢复乙醇 在无毒品动物中进行自我管理。但是，目前尚不清楚是否 过量饮酒的启动受到之间的相互作用的影响 压力，特定的大脑区域和特定基因。当前的建议将 1）研究压力，焦虑和 淘汰小鼠饮用过多； 2）研究神经生物学 慢性乙醇给药，压力和乙醇之间的关系 在淘汰小鼠中的自我管理； 3）确定重要 压力与急性之间关系的神经生物学异常 淘汰小鼠的乙醇给药。这些研究将填补主要空白 在理解压力，大脑区域，遗传学和 饮酒过多的发展。

项目成果

High-throughput behavioral phenotyping in the expanded panel of BXD recombinant inbred strains.

• DOI: 10.1111/j.1601-183x.2009.00540.x
• 发表时间: 2010-03-01
• 期刊: Genes, brain, and behavior
• 作者: Philip VM;Duvvuru S;Gomero B;Ansah TA;Blaha CD;Cook MN;Hamre KM;Lariviere WR;Matthews DB;Mittleman G;Goldowitz D;Chesler EJ
• 通讯作者: Chesler EJ

Chronic intermittent ethanol exposure during adolescence blocks ethanol-induced inhibition of spontaneously active hippocampal pyramidal neurons.

青春期慢性间歇性乙醇暴露可阻断乙醇诱导的自发活跃海马锥体神经元的抑制。

• DOI: 10.1111/j.1530-0277.2006.00020.x
• 发表时间: 2006
• 期刊: Alcoholism, clinical and experimental research.
• 作者: Tokunaga,Sayaka;Silvers,JanelleM;Matthews,DouglasB
• 通讯作者: Matthews,DouglasB

Behavioral effects of ethanol in cerebellum are age dependent: potential system and molecular mechanisms.

乙醇对小脑的行为影响取决于年龄：潜在的系统和分子机制。

• DOI: 10.1111/j.1530-0277.2010.01303.x
• 发表时间: 2010
• 期刊: Alcoholism, clinical and experimental research
• 作者: VanSkike,CandiceE;Botta,Paolo;Chin,VivienS;Tokunaga,Sayaka;McDaniel,JanelleM;Venard,Jacob;Diaz-Granados,JaimeL;Valenzuela,CFernando;Matthews,DouglasB
• 通讯作者: Matthews,DouglasB

Reduced dopamine release in the nucleus accumbens core of adult rats following adolescent binge alcohol exposure: age and dose-dependent analysis.

• DOI: 10.1007/s00213-014-3712-1
• 发表时间: 2015-02
• 期刊: PSYCHOPHARMACOLOGY
• 影响因子: 3.4
• 作者: Zandy, Shannon L.;Matthews, Douglas B.;Tokunaga, Sayaka;Miller, Anthony D.;Blaha, Charles D.;Mittleman, Guy
• 通讯作者: Mittleman, Guy

Dopamine dynamics associated with, and resulting from, schedule-induced alcohol self-administration: analyses in dopamine transporter knockout mice.

• DOI: 10.1016/j.alcohol.2010.12.006
• 发表时间: 2011-06
• 期刊: Alcohol (Fayetteville, N.Y.)
• 作者: Mittleman G;Call SB;Cockroft JL;Goldowitz D;Matthews DB;Blaha CD
• 通讯作者: Blaha CD