Contribution of distinctive outcome measures to the assessment of anxiety in the open field: A meta-analysis of factors mediating open-field test variability in rodent models of anxiety

Abstract

Background: Anxiety and stress-related disorders are severe psychiatric conditions that affect performance in daily tasks. The most common behavioral test to assess a rodent's level of anxiety is a non-invasive open-field test (OFT). To synthesize the many indications of anxiolysis and provide a thorough understanding and more trustworthy conclusions regarding the effects of interventions, a meta-analysis is essential. Methods: Search terms were developed and refined our strategy using MeSH and non-MeSH terms. Here, studies were systematically reviewed on PubMed, Science Direct, Web of Science, Scopus, CINAHL (Ebsco) from July 2023 to September 2024. According to that, 3860 studies were retrieved and after initial and full-text screening 56 studies were included (has stress hormone data) to support finding suitable animal models for future experimental studies on stress-related anxiety. Results: Analyses of the content of reviewed studies supported that stressed female animals present an overall higher time in the center, compared with male animals. The observed difference in time spent in the center between stressed female and male animals can be attributed to various underlying physiological and behavioral mechanisms. On the other hand, the overall effect of stress was not significant on locomotor activity (LA). Stratified subgroup analysis did not find significant effects of species, and meta-regression results showed no significant moderating effects for age and housing conditions. However, a general trend suggested higher LA in control than stressed animals. Conclusion: Anxiety involves multiple interacting psychological drives, meaning no single test can capture all its facets. The OFT's specificity (e.g., showing effects only in stressed females or under certain conditions) should be considered while study is planning. Given the nuanced relationship between locomotion and anxiety, it is imperative to consider additional factors and methodologies when interpreting OFT results.