Global Safety Pharmacology, Drug Safety Research and Development, Pfizer Global Research and Development, Sandwich, CT13 9NJ, UK.
Neurosci Biobehav Rev. 2011 Jan;35(3):912-38. doi: 10.1016/j.neubiorev.2010.10.012. Epub 2010 Oct 29.
The self-administration model is the primary non-clinical approach for assessing the reinforcing properties of novel compounds. Given the now frequent use of rats in self-administration studies, it is important to understand the predictive validity of the rat self-administration model for use in abuse liability assessments. This review of 71 drugs identifies high concordance between findings from rat self-administration studies and two clinical indicators of abuse liability, namely reports of positive subjective-effects and the DEA drug scheduling status. To understand the influence of species on concordance we compare rodent and non-human primate (NHP) self-administration data. In the few instances where discrepancies are observed between rat data and the clinical indicators of abuse liability, rat self-administration data corresponds with NHP data in the majority of these cases. We discuss the influence of genetic factors (sex and strain), food deprivation state and the study design (acquisition or drug substitution) on self-administration study outcomes and highlight opportunities to improve the predictive validity of the self-administration model.
自我给药模型是评估新型化合物强化特性的主要非临床方法。鉴于大鼠在自我给药研究中被频繁使用，了解大鼠自我给药模型在滥用倾向评估中的预测有效性非常重要。本文综述了 71 种药物，发现大鼠自我给药研究的结果与滥用倾向的两个临床指标（即阳性主观效应报告和 DEA 药物分类状态）之间存在高度一致性。为了了解物种对一致性的影响，我们比较了啮齿动物和非人类灵长类动物（NHP）的自我给药数据。在少数情况下，大鼠数据与滥用倾向的临床指标之间存在差异，在这些情况下，大鼠自我给药数据与 NHP 数据大多数情况下一致。我们讨论了遗传因素（性别和品系）、禁食状态和研究设计（获得或药物替代）对自我给药研究结果的影响，并强调了提高自我给药模型预测有效性的机会。
