%0 Journal Article %A Farhan Mohammad %A Joses Ho %A Chun Lei Lim %A Jia Hern Woo %A Dennis Jun Jie Poon %A Bhumika Lamba %A Adam Claridge-Chang %T Anxiety-related interventions in rodent defense behaviors: systematic review and meta-analyses %D 2015 %R 10.1101/020701 %J bioRxiv %P 020701 %X Background Assays measuring defense behavior in rodents, including the elevated plus maze, open field and light-dark box assays, have been widely used in preclinical models of anxiety to study the ability of therapeutic interventions to modulate the anxiety-like state. However, many important proposed anxiety-modulating factors, including genes, drugs and stressors have had paradoxical effects in these assays across different studies.Objectives We performed a systematic review and meta-analysis of the literature on the effect of anxiety-targeted interventions on rodent defense behaviors in three commonly-used assays: the elevated plus maze, open field and light-dark box assays. Our aim was to determine the effect sizes of a panel of purported anxiety-related interventions across three assays.Data Sources Using PubMed and EMBASE search phrases to identify articles, a systematic review was conducted on a panel of ten anxiety-linked interventions: diazepam, 5-HT1A receptor knockout and overexpression, SERT knockout and overexpression, pain, restraint, social isolation, corticotropin-releasing hormone and Crhr1. In addition, an ad hoc literature search was used to identify articles studying the effects of two genes that are not related to anxiety behaviours in rodents: adenylyl cyclase 1 and synaptotagmin.Study Eligibility Criteria Articles were included if they contained data on the effects of any one of the abovementioned anxiety factors on one of the three rodent defense behaviors.Synthesis Methods Systematic meta-analyses were conducted; synthesis of the data was performed using random effects models of Hedges’ g.Results Eight of the ten anxiety-related interventions had statistically significant effects on rodent defense behavior, while Htr1a overexpression and Crh knockout did not. Evidence for publication bias was found in three interventions: diazepam, Htt knockout, and social isolation.Limitations This meta-analysis excluded unpublished and non-English studies; publication bias and heterogeneity were identified in several meta-analyses.Conclusions The synthetic data support eight of the ten proposed anxiety factors as having moderate or large effects on rodent anxiety as measured by ARDEB assay (diazepam, Htr1a knockout, Htr1a overexpression, Htt knockout, Htt overexpression, pain, restraint and Crhr1 knockout). Two interventions has small effects on rodent anxiety: social isolation and Crh knockout. %U https://www.biorxiv.org/content/biorxiv/early/2015/11/18/020701.full.pdf