What Aspects of Human Alcohol Use Disorders Can Be Modeled Using Selectively Bred Rat Lines?
What Aspects of Human Alcohol Use Disorders Can Be Modeled Using Selectively Bred Rat Lines?
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DOI：
10.3109/10826084.2010.482424
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发表时间：
2010-09-01
影响因子：
2
通讯作者：
Froehlich, J. C.
中科院分区：
文献类型：
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作者：
Froehlich, J. C.
利用选择性育种产生用于研究酒精滥用和酗酒的动物模型代表了酒精研究领域的重大进展之一。针对酒精偏好和不偏好酒精选择性培育的大鼠对于酒精研究界的临床前和临床研究人员来说非常有用，可用于研究饮酒的行为、神经生物学和分子基础，识别可能导致酒精滥用和酒精中毒发展的基因，以及评估旨在减少酒精摄入和预防酒精复发的药物的效用。选择性饲养的酒精偏好大鼠（酒精偏好或“P”系）对低剂量酒精增强作用的反应性增强，对中/高剂量酒精的厌恶程度较低，并且能够比选择性饲养的不偏好酒精（酒精不偏好或“NP”系）的大鼠更快地产生对酒精厌恶作用的耐受性，并且维持耐受性的时间更长。低剂量酒精作为 P 大鼠增强剂的效力增强可能会促进和维持饮酒。 P 系对中/高剂量酒精药理作用的厌恶较弱，使得 P 大鼠比 NP 大鼠在摄入后效应变得厌恶之前喝更多的酒精。通过反复自愿饮酒，快速诱导对酒精厌恶作用的耐受性，以及 P 系大鼠持续的酒精耐受性可能有助于维持饮酒。这些都是强大的机制，可以促进和维持大量饮酒行为。尽管这些大鼠品系已被用来解决人类过度饮酒的几个特征，但它们尚未用于模拟人类酒精使用障碍的几个方面。讨论了这些选择性培育的大鼠品系的新应用，这可能会进一步加深我们对导致酒精滥用和酗酒的因素的理解。
The use of selective breeding to produce animal models for the study of alcohol abuse and alcoholism represents one of the major advances in the field of alcohol research. Rats selectively bred for alcohol preference and alcohol nonpreference have been useful to both preclinical and clinical investigators in the alcohol research community for studying the behavioral, neurobiological, and molecular basis of alcohol drinking, for identifying the genes that may contribute to the development of alcohol abuse and alcoholism, and for evaluating the utility of drugs aimed at reducing alcohol intake and preventing alcohol relapse. Rats selectively bred for alcohol preference (alcohol preferring or "P" line) have enhanced responsiveness to the low dose reinforcing effects of alcohol, less aversion to moderate/high doses of alcohol, and are able to develop tolerance to the aversive effects of alcohol more rapidly and to maintain tolerance longer than rats selectively bred for alcohol nonpreference (alcohol nonpreferring or "NP" line). The increased potency of low-dose alcohol as a reinforcer for P rats might be expected to foster and maintain alcohol drinking. Weaker aversion to the pharmacological effects of moderate/high doses of alcohol in the P line would allow P rats to drink more alcohol than NP rats before the postingestional effects become aversive. Rapid induction of tolerance to the aversive effects of alcohol with repeated bouts of voluntary alcohol drinking, as well as persistence of alcohol tolerance in rats of the P line might serve to maintain alcohol drinking. These are powerful mechanisms that may serve to promote and maintain a high alcohol drinking behavior. Although these rat lines have been used to address several characteristics of excessive alcohol consumption in humans, they have not yet been used to model several aspects of human alcohol use disorders. New applications of these selectively bred rat lines are discussed which may further our understanding of the factors contributing to alcohol abuse and alcoholism.