The validity of widely used rodent behavioural tests of anxiety has been questioned, as they often fail to produce consistent results across independent replicate studies. In this study, we assessed the sensitivity of common behavioural tests of anxiety in mice to detect anxiolytic effects of drugs prescribed to treat anxiety in humans. We conducted a pre-registered systematic review of 814 studies reporting effects of 25 anxiolytic compounds using common behavioural tests for anxiety. Meta-analyses of effect sizes of treatments showed that only two out of 17 commonly used test measures reliably detected effects of anxiolytic compounds. We report considerable between-study variation in size and even direction of effects of most anxiolytics on most outcome variables. Our findings indicate a general lack of sensitivity of those behavioural tests and cast serious doubt on both construct and predictive validity of most of these tests. In view of scientifically valid and ethically responsible research, we call for a revision of behavioural tests of anxiety in mice and the development of more predictive tests.
Keywords: Anxiety; Anxiolytics; Behavioural tests; Benzodiazepines; Elevated plus maze; Elevated zero maze; Four-plate test; Holeboard test; Light-dark box; Mouse; Novelty suppressed feeding; Open field test; Pre-clinical; Reproducibility; SNRIs; SSRIs; Sensitivity; Social interaction test; Staircase test; TCAs.
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.