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: 6195131
• 负责人: TING-KAI K LI
• 金额: $ 52.03万
• 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/6195131
• 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：（改编自研究者摘要） 本研究的长期目标是调查 大鼠对乙醇自身给药的乙醇耐受性 选择性地培育高和低口服酒精饮料。一系列的研究 将检查高和低酒精饮用（HAD 1 /LAD I）的重复对 和HAD 2/LAD 2）系，以确定是否存在遗传相关 饮酒倾向与饮酒量之间的关系 对乙醇的运动损伤效应的敏感性和耐受性。一 乙醇敏感性的参数检查，急性（疗程内）和 将进行慢性（疗程之间）耐受。第二系列 研究将检验这一假设，即对 乙醇在乙醇自身给药期间产生。此外， 这种耐受性的变化可能会在乙醇饮用的收购过程中， 反应，并作为大鼠的乙醇饮用史的函数。第三 一系列的研究是基于这样的假设，即高乙醇偏好可能 与神经兴奋状态有关。该状态产生P3 诱发反应电位（ERP）范式中的一个成分， 酒精偏好的P大鼠相对于非偏好的NP大鼠，并可能产生 酒精偏好大鼠的声惊吓反应增强。提出 实验将检查P和NP大鼠，以确定 乙醇对ERP和声惊吓的影响。急性耐受性 将检查乙醇对P和NP大鼠的ERP和运动协调的影响 使用可以维持血液乙醇水平的血液乙醇钳夹程序 在预定的稳定状态下持续延长的时间段。主要的假设是， 将被测试的是，选择性育种的高和低酒精摄入量将 与对厌恶和 乙醇的运动损伤作用和乙醇减弱 CNS过度兴奋的神经生理和行为表现。