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      A Systematic Review and Meta-Analysis of the Relationship Between Social Dominance Status and Common Behavioral Phenotypes in Male Laboratory Mice

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          Abstract

          Background: Social dominance status (e.g., dominant or subordinate) is often associated with individual differences in behavior and physiology but is largely neglected in experimental designs and statistical analysis plans in biomedical animal research. In fact, the extent to which social dominance status affects common experimental outcomes is virtually unknown. Given the pervasive use of laboratory mice and culminating evidence of issues with reproducibility, understanding the role of social dominance status on common behavioral measures used in research may be of paramount importance.

          Methods: To determine whether social dominance status—one facet of the social environment—contributes in a systematic way to standard measures of behavior in biomedical science, we conducted a systematic review of the existing literature searching the databases of PubMed, Embase, and Web of Science. Experiments were divided into several domains of behavior: exploration, anxiety, learned helplessness, cognition, social, and sensory behavior. Meta-analyses between experiments were conducted for the open field, elevated plus-maze, and Porsolt forced swim test.

          Results: Of the 696 publications identified, a total of 55 experiments from 20 published studies met our pre-specified criteria. Study characteristics and reported results were highly heterogeneous across studies. A systematic review and meta-analyses, where possible, with these studies revealed little evidence for systematic phenotypic differences between dominant and subordinate male mice.

          Conclusion: This finding contradicts the notion that social dominance status impacts behavior in significant ways, although the lack of an observed relationship may be attributable to study heterogeneity concerning strain, group-size, age, housing and husbandry conditions, and dominance assessment method. Therefore, further research considering these secondary sources of variation may be necessary to determine if social dominance generally impacts treatment effects in substantive ways.

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          Most cited references66

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          Conducting Meta-Analyses inRwith themetaforPackage

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            SYRCLE’s risk of bias tool for animal studies

            Background Systematic Reviews (SRs) of experimental animal studies are not yet common practice, but awareness of the merits of conducting such SRs is steadily increasing. As animal intervention studies differ from randomized clinical trials (RCT) in many aspects, the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies. The Cochrane Collaboration developed a Risk of Bias (RoB) tool to establish consistency and avoid discrepancies in assessing the methodological quality of RCTs. A similar initiative is warranted in the field of animal experimentation. Methods We provide an RoB tool for animal intervention studies (SYRCLE’s RoB tool). This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies. To enhance transparency and applicability, we formulated signalling questions to facilitate judgment. Results The resulting RoB tool for animal studies contains 10 entries. These entries are related to selection bias, performance bias, detection bias, attrition bias, reporting bias and other biases. Half these items are in agreement with the items in the Cochrane RoB tool. Most of the variations between the two tools are due to differences in design between RCTs and animal studies. Shortcomings in, or unfamiliarity with, specific aspects of experimental design of animal studies compared to clinical studies also play a role. Conclusions SYRCLE’s RoB tool is an adapted version of the Cochrane RoB tool. Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies. This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the methodological quality of animal studies.
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              Shyness and boldness in humans and other animals.

              The shy-bold continuum is a fundamental axis of behavioral variation in humans and at least some other species, but its taxonomic distribution and evolutionary implications are unknown. Models of optimal risk, density- or frequency-dependent selection, and phenotypic plasticity can provide a theoretical framework for understanding shyness and boldness as a product of natural selection. We sketch this framework and review the few empirical studies of shyness and boldness in natural populations. The study of shyness and boldness adds an interesting new dimension to behavioral ecology by focusing on the nature of continuous behavioral variation that exists within the familiar categories of age, sex and size. Copyright © 1994. Published by Elsevier Ltd.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                20 January 2021
                2020
                : 14
                : 624036
                Affiliations
                [1] 1Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida , Gainesville, FL, United States
                [2] 2Division of Animal Welfare, Veterinary Public Health Institute, Universität Bern , Bern, Switzerland
                [3] 3Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center , Lubbock, TX, United States
                [4] 4Department of Civil, Environmental, and Construction Engineering, Texas Tech University , Lubbock, TX, United States
                [5] 5Department of Biology, College of Liberal Arts and Sciences, University of Florida , Gainesville, FL, United States
                Author notes

                Edited by: Tim Karl, Western Sydney University, Australia

                Reviewed by: Aki Takahashi, University of Tsukuba, Japan; Thiago C. Moulin, Uppsala University, Sweden

                *Correspondence: Justin A. Varholick j.a.varholick@ 123456gmail.com

                This article was submitted to Pathological Conditions, a section of the journal Frontiers in Behavioral Neuroscience

                Article
                10.3389/fnbeh.2020.624036
                7855301
                33551768
                e0372fba-64b8-4147-a4b0-771019040b7d
                Copyright © 2021 Varholick, Bailoo, Jenkins, Voelkl and Würbel.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 October 2020
                : 15 December 2020
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 71, Pages: 13, Words: 10257
                Funding
                Funded by: European Research Council 10.13039/501100000781
                Award ID: 322576
                Categories
                Behavioral Neuroscience
                Systematic Review

                Neurosciences
                social dominance,behavior,systematic review,meta-analysis,reproducibility,preclinical,experimental design

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