The predictive validity of the rat self-administration model for abuse liability

• Published in: Neuroscience and biobehavioral reviews 2011-01, Vol.35 (3), p.912-938
• Main Authors: O’Connor, Eoin C., Chapman, Kathryn, Butler, Paul, Mead, Andy N.
• Format: Article
• Language: English
• Subjects: Abuse potential; Animals; Behavioral psychophysiology; Biological and medical sciences; Dependence; Disease Models, Animal; Drug Administration Schedule; Food Deprivation; Fundamental and applied biological sciences. Psychology; Humans; Non-human primate; Predictive Value of Tests; Primates; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rat; Rats; Reinforcement; Reproducibility of Results; Research Design; Scheduling; Self Administration; Subjective-effects; Substance-Related Disorders - physiopathology; Substance-Related Disorders - psychology
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2010.10.012

▶ The rat self-administration model has high predictive validity for abuse liability. ▶ This review underwrites the use of rats in assessments of abuse liability. ▶ Methodological variables that may influence predictive validity are discussed. ▶ Opportunities to improve the predictive validity of the model are proposed. 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.