Similarities and dissimilarities in the effects of benzodiazepines and specific serotonin reuptake inhibitors (SSRIs) in the defensive marble burying test: A systematic review and meta-analysis

One problem areas of animal models and tests for neuropsychiatric disorders is unclear reproducibility, including both internal and external validity. One way to examine external validity is with systematic reviews and meta-analyses, a standard practice in clinical research that is relatively neglected in preclinical research. Considering the need to evaluate the validity and reproducibility of frequently used animal models, this study presents a meta-analysis of the effects of prototypic benzodiazepines and specific serotonin reuptake inhibitors (SSRIs) in the mouse defensive marble burying test (MBT). These drug groups were selected because although they differ in their biological targets as well as in their clinical use, they are both commonly used for the treatment of anxiety disorders. A PubMed literature search was performed to identify studies that examined the effects of benzodiazepines (diazepam, alprazolam, chlordiazepoxide, clonazepam) or SSRIs (fluoxetine, citalopram, escitalopram, fluvoxamine, paroxetine) in the MBT in mice. For benzodiazepines, 73 experiments were included. Benzodiazepines effect size was 2.04 and Q statistics was 1959 with a significant correlation between dose and effect size (r = 0.31, p = 0.007). For SSRIs we identified 47 experiments. Effect size of SSRIs was 2.24 and Q statistics was 493.38. No correlation was found between dose and effect size (r = 0.23, p = 0.12). The current results support the external validity of the defensive marble burying test as a screening test for anxiolytic effects. However, these results indicate that significant attention should be given to the administration schedules of benzodiazepines and SSRIs.