ALCOHOL TOLERANCE IN RAT LINES SELECTED FOR PREFERENCE

优先选择的大鼠系的酒精耐受性

• 批准号: 6345825
• 负责人: TING-KAI K LI
• 金额: $ 9.96万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6345825
• 关键词: alcoholic beverage consumption; behavior test; behavioral genetics; behavioral habituation /sensitization; drug tolerance; evoked potentials; family genetics; genetic susceptibility; laboratory rat; neurophysiology; preference; psychomotor function; reflex; self medication; startle reaction

DESCRIPTION: (Adapted from the Investigator's Abstract) The long term objective of this research is to investigate the relationship of ethanol tolerance to the self-administration of ethanol in lines of rats selectively bred for high and low oral ethanol drinking. One series of studies will examine the replicate pairs of high and low alcohol drinking (HAD 1 /LAD I and HAD2/LAD2) lines to determine whether there is a genetic correlation between the predisposition to consume high and low amounts of alcohol and the sensitivity and tolerance to the motor-impairing effects of ethanol. A parametric examination of ethanol sensitivity, acute (within-session) and chronic (between-session) tolerance will be carried out. A second series of studies will test the hypothesis that tolerance to the aversive effects of ethanol develops during ethanol self-administration. Furthermore, the magnitude of this tolerance may change during the acquisition of the ethanol drinking response and as a function of the rats' ethanol drinking history. A third series of studies is based on the hypothesis that high ethanol preference may be associated with a state of neuroexcitability. This state produces a P3 component in an evoked response potential (ERP) paradigm that is reduced in alcohol-preferring P rats relative to non-preferring NP rats and may produce an enhanced acoustic startle response in alcohol-preferring rats. Proposed experiments will examine P and NP rats to determine any line differences in the effects of ethanol on ERP and acoustic startle. Acute tolerance to the effects of ethanol on ERP and motor coordination in P and NP rats will be examined using a blood ethanol clamp procedure which can maintain blood ethanol levels at a predetermined steady state for prolonged periods. The main hypothesis that will be tested is that selective breeding for high and low alcohol intake will be correlated with differential tolerance development to the aversive and motor-impairing effects of ethanol and to the ability of ethanol to attenuate neuro-physiological and behavioral manifestations of CNS hyperexcitability.

描述：（根据调查员的摘要进行了改编） 这项研究的长期目标是调查 乙醇对乙醇在大鼠线中的自我给药的耐受性 有选择地繁殖高口服乙醇和低口服乙醇。一系列研究 将检查高饮酒和低饮酒的重复对（有1个 /小伙子I 并有2/lad2）线以确定是否存在遗传相关性 在消费高量和低酒精的倾向与 对乙醇的运动障碍作用的敏感性和耐受性。一个 参数检查乙醇敏感性，急性（会议内）和 将执行慢性（会议间）公差。第二系列 研究将检验以下假设 乙醇在乙醇自我给药过程中发展。此外，大小 在获取乙醇饮酒期间，这种耐受性可能会改变 反应和与大鼠乙醇饮酒史的关系。第三 一系列研究基于以下假设：高乙醇偏好可能 与神经脱颖而出的状态相关。该状态产生P3 诱发响应电位（ERP）范式中的组成部分减少 相对于非偏爱的NP大鼠，饮酒的P大鼠占P大鼠，可能会产生 在饮酒大鼠中增强了气声反应。建议的 实验将检查P和NP大鼠，以确定该线的任何差异 乙醇对ERP和声学惊吓的影响。对影响的急性耐受性 将检查ERP上的乙醇和P和NP大鼠的运动协调 使用可以维持血液乙醇水平的血液乙醇夹具 在长时间的预定稳态下。主要假设是 将测试的是，高酒精摄入量的选择性育种将 与厌恶性的差异耐受性发展相关， 乙醇的运动障碍作用以及乙醇减弱的能力 中枢神经系统过度兴奋性的神经生理和行为表现。