Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22904, USA.
Pharmacol Biochem Behav. 2018 Jan;164:50-61. doi: 10.1016/j.pbb.2017.06.006. Epub 2017 Jun 15.
An increasing emphasis has been placed on the development and use of animal models of addiction that capture defining features of human drug addiction, including escalation/binge drug use, enhanced motivation for the drug, preference for the drug over other reward options, use despite negative consequences, and enhanced drug-seeking/relapse vulnerability. The need to examine behavior in both males and females has also become apparent given evidence demonstrating that the addiction process occurs differently in males and females. This review discusses the procedures that are used to model features of addiction in animals, as well as factors that influence their development. Individual differences are also discussed, with a particular focus on sex differences. While no one procedure consistently produces all characteristics, different models have been developed to focus on certain characteristics. A history of escalating/binge patterns of use appears to be critical for producing other features characteristic of addiction, including an enhanced motivation for the drug, enhanced drug seeking, and use despite negative consequences. These characteristics tend to emerge over abstinence, and appear to increase rather than decrease in magnitude over time. In females, these characteristics develop sooner during abstinence and/or following less drug exposure as compared to males, and for psychostimulant addiction, may require estradiol. Although preference for the drug over other reward options has been demonstrated in non-human primates, it has been more difficult to establish in rats. Future research is needed to define the parameters that optimally induce each of these features of addiction in the majority of animals. Such models are essential for advancing our understanding of human drug addiction and its treatment in men and women.
人们越来越重视开发和使用能够捕捉人类药物成瘾定义特征的动物成瘾模型，包括药物滥用/狂欢、增强对药物的动机、对药物的偏好超过其他奖励选择、不顾负面后果而使用药物以及增强药物寻求/复发易感性。鉴于有证据表明，男性和女性的成瘾过程存在差异，因此也需要研究男性和女性的行为。本文讨论了用于在动物中模拟成瘾特征的程序，以及影响其发展的因素。还讨论了个体差异，特别关注性别差异。虽然没有一种程序能够始终如一地产生所有特征，但已经开发出不同的模型来关注某些特征。使用模式的不断升级/狂欢似乎对于产生其他成瘾特征至关重要，包括对药物的增强动机、增强的药物寻求以及不顾负面后果而使用药物。这些特征往往在禁欲期间出现，并随着时间的推移似乎会增加而不是减少。在女性中，这些特征在禁欲期间或在暴露于较少药物后比男性更早出现，并且对于精神兴奋剂成瘾，可能需要雌二醇。尽管在非人类灵长类动物中已经证明了对药物的偏好超过其他奖励选择，但在大鼠中更难建立。未来的研究需要确定在大多数动物中最佳诱导这些成瘾特征的参数。这些模型对于我们理解男性和女性的人类药物成瘾及其治疗至关重要。
