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: 6371382
• 负责人: TING-KAI K LI
• 金额: $ 66.8万
• 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: 2000-07-12 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6371382
• 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：（改编自研究者的摘要） 本研究的长期目标是调查以下因素之间的关系： 大鼠对自我施用乙醇的乙醇耐受性 选择性培育用于高或低口服乙醇饮用量。一系列研究 将检查高酒精度和低度酒精饮酒的重复对（HAD 1 /LAD I 和 HAD2/LAD2) 系以确定是否存在遗传相关性 摄入大量酒精和少量酒精的倾向之间 对乙醇运动损伤作用的敏感性和耐受性。一个 乙醇敏感性参数检查，急性（会话内）和 将进行慢性（疗程间）耐受。第二个系列 研究将检验这样的假设：对不良影响的耐受性 乙醇在自我给药过程中产生。此外，幅度 在获得乙醇饮用过程中，这种耐受性可能会发生变化 反应以及大鼠乙醇饮用史的函数。第三个 系列研究基于这样的假设：高乙醇偏好可能 与神经兴奋状态有关。这个状态产生一个P3 诱发反应电位（ERP）范式中的一个组成部分，其减少 与不偏好 NP 大鼠相比，偏好酒精的 P 大鼠可能会产生 增强嗜酒大鼠的声音惊吓反应。建议的 实验将检查 P 和 NP 大鼠以确定 乙醇对 ERP 和声惊吓的影响。对影响的急性耐受性 将检查乙醇对 P 和 NP 大鼠 ERP 和运动协调的影响 使用血液乙醇钳夹程序可以维持血液乙醇水平 长时间处于预定的稳定状态。主要假设是 将测试的是，针对高酒精摄入量和低酒精摄入量的选择性育种将 与对厌恶和厌恶事物的不同耐受性发展相关 乙醇的运动损伤作用以及乙醇减弱的能力 中枢神经系统过度兴奋的神经生理和行为表现。