Bell Richard L, Rodd Zachary A, Lumeng Lawrence, Murphy James M, McBride William J
Department of Psychiatry, Indiana University School of Medicine, USA.
Addict Biol. 2006 Sep;11(3-4):270-88. doi: 10.1111/j.1369-1600.2005.00029.x.
The alcohol-preferring, P, rat was developed by selective breeding to study ethanol drinking behavior and its consequences. Characterization of this line indicates the P rat meets all of the criteria put forth for a valid animal model of alcoholism, and displays, relative to their alcohol-non-preferring, NP, counterparts, a number of phenotypic traits associated with alcohol abuse and alcoholism. Behaviorally, compared with NP rats, P rats are less sensitive to the sedative and aversive effects of ethanol and more sensitive to the stimulatory effects of ethanol. Neurochemically, research with the P line indicates the endogenous dopaminergic, serotonergic, GABAergic, opiodergic, and peptidergic systems may be involved in a predisposition for alcohol abuse and alcoholism. Paralleling the clinical literature, genetically selected P rats display levels of ethanol intake during adolescence comparable to that seen during adulthood. Binge drinking has been associated with an increased risk for health and other problems associated with ethanol abuse. A model of binge-like drinking during the dark cycle indicates that P rats will consume 6 g/kg/day of ethanol in as little as three 1-hour access periods/day, which approximates the 24-hour intake of P rats with free-choice access to a single concentration of ethanol. The alcohol deprivation effect (ADE) is a transient increase in ethanol intake above baseline values upon re-exposure to ethanol access after an extended period of deprivation. The ADE has been proposed to be an animal model of relapse behavior, with the adult P rat displaying a robust ADE after prolonged abstinence. Overall, these findings indicate that the P rat can be effectively used in models assessing alcohol-preference, a genetic predisposition for alcohol abuse and/or alcoholism, and excessive drinking using protocols of binge-like or relapse-like drinking.
嗜酒的P品系大鼠是通过选择性育种培育出来的,用于研究乙醇饮用行为及其后果。该品系的特征表明,P大鼠符合为酒精中毒有效动物模型提出的所有标准,并且相对于不嗜酒的NP品系大鼠,表现出许多与酒精滥用和酒精中毒相关的表型特征。在行为方面,与NP大鼠相比,P大鼠对乙醇的镇静和厌恶作用不太敏感,而对乙醇的刺激作用更敏感。在神经化学方面,对P品系的研究表明,内源性多巴胺能、5-羟色胺能、γ-氨基丁酸能、阿片样物质能和肽能系统可能与酒精滥用和酒精中毒的易感性有关。与临床文献一致,经基因选择的P大鼠在青春期的乙醇摄入量水平与成年期相当。暴饮已被认为与乙醇滥用相关的健康和其他问题风险增加有关。在暗周期进行的类似暴饮的饮酒模型表明,P大鼠每天只需在三个1小时的饮酒时间段内就能摄入6克/千克的乙醇,这接近自由选择单一浓度乙醇的P大鼠24小时的摄入量。酒精剥夺效应(ADE)是指在长时间剥夺乙醇摄入后重新接触乙醇时,乙醇摄入量会短暂高于基线值。ADE被认为是复发行为的动物模型,成年P大鼠在长期禁欲后会表现出强烈的ADE。总体而言,这些发现表明,P大鼠可有效地用于评估酒精偏好、酒精滥用和/或酒精中毒的遗传易感性以及使用类似暴饮或类似复发饮酒方案进行过度饮酒的模型。