title: Concordance and incongruence in preclinical anxiety models: Systematic review and meta-analyses.
abstract: Rodent defense behavior assays have been widely used as preclinical models of anxiety to study possibly therapeutic anxiety-reducing interventions. However, some proposed anxiety-modulating factors - genes, drugs and stressors - have had discordant effects across different studies. To reconcile the effect sizes of purported anxiety factors, we conducted systematic review and meta-analyses of the literature on ten anxiety-linked interventions, as examined in the elevated plus maze, open field and light-dark box assays. Diazepam, 5-HT1A receptor gene knockout and overexpression, SERT gene knockout and overexpression, pain, restraint, social isolation, corticotropin-releasing hormone and Crhr1 were selected for review. Eight interventions had statistically significant effects on rodent anxiety, while Htr1a overexpression and Crh knockout did not. Evidence for publication bias was found in the diazepam, Htt knockout, and social isolation literatures. The Htr1a and Crhr1 results indicate a disconnect between preclinical science and clinical research. Furthermore, the meta-analytic data confirmed that genetic SERT anxiety effects were paradoxical in the context of the clinical use of SERT inhibitors to reduce anxiety.
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, 138673, Singapore.
authors.forename: Farhan
authors.initials: F
authors.lastname: Mohammad
authors.affiliation: Institute for Molecular and Cell Biology, Agency for Science Technology and Research, 138673, Singapore.
authors.forename: Joses
authors.initials: J
authors.lastname: Ho
authors.affiliation: Institute for Molecular and Cell Biology, Agency for Science Technology and Research, 138673, Singapore.
authors.forename: Jia Hern
authors.initials: JH
authors.lastname: Woo
authors.affiliation: Institute for Molecular and Cell Biology, Agency for Science Technology and Research, 138673, Singapore.
authors.forename: Chun Lei
authors.initials: CL
authors.lastname: Lim
authors.affiliation: Institute for Molecular and Cell Biology, Agency for Science Technology and Research, 138673, Singapore.
authors.forename: Dennis Jun Jie
authors.initials: DJJ
authors.lastname: Poon
authors.affiliation: Institute for Molecular and Cell Biology, Agency for Science Technology and Research, 138673, Singapore.
authors.forename: Bhumika
authors.initials: B
authors.lastname: Lamba
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, 138673, Singapore; Institute for Molecular and Cell Biology, Agency for Science Technology and Research, 138673, Singapore; Department of Physiology, National University of Singapore, 138673, Singapore. Electronic address: claridge-chang.adam@duke-nus.edu.sg.
authors.forename: Adam
authors.initials: A
authors.lastname: Claridge-Chang
mesh_terms: D001007:Anxiety; D001008:Anxiety Disorders; D003346:Corticotropin-Releasing Hormone; D006801:Humans; D018019:Receptors, Corticotropin-Releasing Hormone; D012934:Social Isolation
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone
keywords: Anxiety; Behavior; Corticotropin releasing hormone; Defense; Isolation; Meta-analysis; Pain; Receptor; Rodent; Serotonin; Stress; Transporter