The purpose of this review is to discuss ways to think about and study sex differences in preclinical animal models. We use the framework of addiction, in which animal models have excellent face and construct validity, to illustrate the importance of considering sex differences. There are four types of sex differences: qualitative, quantitative, population, and mechanistic. A better understanding of the ways males and females can differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating. We have outlined major quantitative, population, and mechanistic sex differences in the addiction domain using a heuristic framework of the three established stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Female rats, in general, acquire the self-administration of drugs and alcohol more rapidly, escalate their drug taking with extended access more rapidly, show more motivational withdrawal, and (where tested in animal models of "craving") show greater reinstatement. The one exception is that female rats show less motivational withdrawal to alcohol. The bases for these quantitative sex differences appear to be both organizational, in that estradiol-treated neonatal animals show the male phenotype, and activational, in that the female phenotype depends on the effects of gonadal hormones. In animals, differences within the estrous cycle can be observed but are relatively minor. Such hormonal effects seem to be most prevalent during the acquisition of drug taking and less influential once compulsive drug taking is established and are linked largely to progesterone and estradiol. This review emphasizes not only significant differences in the phenotypes of females and males in the domain of addiction but emphasizes the paucity of data to date in our understanding of those differences.

中文翻译：

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动物模型中的性别差异：关注成瘾。

本文的目的是讨论在临床前动物模型中思考和研究性别差异的方法。我们使用成瘾的框架（其中动物模型具有出色的面孔和构造效度）来说明考虑性别差异的重要性。性别差异有四种类型：定性，定量，总体和机制。更好地了解男性和女性之间的差异方式将有助于科学家设计实验，以更好地表征他们正在研究的新现象中性别差异的存在与否。我们使用成瘾周期的三个既定阶段的启发式框架概述了成瘾领域中的主要定量，人口和机械性别差异：暴饮暴食/中毒，戒断/负面影响，和专注/期待。通常，雌性大鼠较快地获得药物和酒精的自我给药，随着服药的扩展而迅速增加其用药量，表现出更多的动机性戒断，并且（在“渴望”的动物模型中进行了测试）显示出更大的恢复性。一个例外是雌性大鼠对酒精的动机戒断较少。这些数量上的性别差异的基础似乎是组织性的，因为雌二醇处理的新生动物表现出雄性表型，而活化性则表现出雌性表型取决于性腺激素的作用。在动物中，可以观察到发情周期内的差异，但差异较小。这种激素作用在获得药物过程中似乎最为普遍，一旦确立了强制药物的作用，其影响就较小，并且很大程度上与孕酮和雌二醇有关。这篇综述不仅着重于成瘾领域中男女表型的显着差异，而且强调了迄今为止我们对这些差异的理解尚缺乏数据。