Individual differences in drug dependence in rats: The role of genetic factors and life events
Individual differences in drug dependence in rats: The role of genetic factors and life events
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DOI：
10.1016/j.ejphar.2005.09.032
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发表时间：
2005-12-05
影响因子：
5
通讯作者：
Cools, AR
中科院分区：
文献类型：
--
作者：
Ellenbroek, BA;van der Kam, EL;Cools, AR
药物依赖和成瘾是一种慢性精神疾病，在经济损失、保健费用和司法问题方面对社会产生深远影响。药物成瘾的一个关键问题是，其病因学涉及哪些因素，特别是什么介导了从使用到滥用的大便。与大多数其他精神疾病一样，成瘾最好用所谓的三击模型来描述，该模型指出疾病是遗传因素、早期谎言事件和晚期环境因素之间相互作用的结果。然而，这些因素的确切性质仍有待阐明。本综述讨论了这三种不同的命中目前正在调查的动物模型的结果。阿扑吗啡敏感（APO-SUS）和阿扑吗啡不敏感（APO-UNSUS）大鼠，最初选择的基础上，他们的行为反应的多巴胺能激动剂阿扑吗啡，最近被发现是遗传不同的基因拷贝数的一个组成部分的γ-分泌酶复合物称为Aph-1b。而APO-UNSUS大鼠有三个拷贝的基因，APO-SUS大鼠有1或2个拷贝。此外，我们已经表明，这些大鼠表现出可卡因和酒精自我管理的差异，以及早期的生活事件和后期的环境因素可以改变这种自我管理的行为。因此，迄今为止的数据支持这样的假设，即APO-SUS和APO-UNSUS大鼠提供了一种有趣的药物依赖性动物模型，其中基因和环境相互作用。最后，我们提出了一个理论模型，可以解释这种基因-环境相互作用。(c)2005 Elsevier B. V.保留所有权利。
Drug dependence and addiction is a chronic mental illness that has far reaching consequences for society in terms of economic loss, health costs and judicial problems. A crucial question in drug addiction, is what factors are involved in its aetiology, and especially what mediates the shit from use to abuse. As in most other mental illnesses, addiction can best be described using the so-called three hit model, which states that a disease results from an interaction between genetic factors, early lie events and late environmental factors. However, the precise nature of these factors still remains to be elucidated.This present review discusses the results from an animal model in which these three different hit are currently being investigated. The apomorphine susceptible (APO-SUS) and apomorphine unsusceptible (APO-UNSUS) rats, originally selected on the basis of their behavioural response to the dopaminergic agonist apomorphine, were recently found to be genetically different in the number of gene copies of a component of the gamma-secretase complex called Aph-1b. Whereas APO-UNSUS rats have three copies of the gene, APO-SUS rats have either 1 or 2 copies. In addition we have shown that these rats show differences in cocaine and alcohol self-administration, and that both early life events and late environmental factors can alter this self-administration behaviour. Thus, the data so far support the hypothesis that the APO-SUS and APO-UNSUS rats offer an interesting animal model for drug dependence in which genes and environment interact. We finally propose a theoretical model which can explain this gene-environment interaction. (c) 2005 Elsevier B.V. All rights reserved.