ALCOHOL TOLERANCE IN RAT LINES SELECTED FOR PREFERENCE

描述：(改编自《调查者摘要》) 这项研究的长期目标是调查 大鼠对乙醇自身给药的耐受性 专为饮用高、低剂量的口服酒精而选育。一系列研究 我将检查重复的高酒精和低酒精饮酒对(HAD 1/LAD I 和HAD2/LAD2)系，以确定是否存在遗传相关性 在饮酒量高或低的倾向与 对乙醇的运动损伤效应的敏感性和耐受性。一个 急性(会中)和酒精敏感性的参数检查 将实行长期(间歇期)容忍。第二个系列 研究将检验这样一种假设，即对 乙醇在乙醇自我给药过程中形成。此外，震级 这种耐受性可能会在获得酒精饮酒期间发生变化 反应和作为大鼠饮酒史的函数。三分之一 一系列研究是基于这样一个假设，即高度的乙醇偏好可能 与神经兴奋性状态有关。这种状态会产生P3 诱发反应电位(ERP)范例中的组件，在 嗜酒的P鼠与非嗜酒的NP鼠相比，可能产生 酒精嗜好大鼠的声学惊吓反应增强。建议 实验将检查P和NP大鼠，以确定在 乙醇对事件相关电位和听性惊厥的影响对这些影响的急性耐受性 乙醇对P和NP大鼠事件相关电位和运动协调性的影响 使用血液酒精钳夹程序，可以维持血液酒精水平 长时间处于预定的稳定状态。主要的假设是 将受到考验的是高酒精摄入量和低酒精摄入量的选择性育种将 与发展对厌恶者和 乙醇的运动损伤作用及对其衰减能力的影响 中枢神经系统高兴奋性的神经生理和行为表现。

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.