Concordance and incongruence in preclinical anxiety models: Systematic review and meta-analyses

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

卷:68

Review

Mohammad, Farhan¹  Ho, Joses²  Woo, Jia Hem²  Lim, Chun Lei²  Poon, Dennis Jun Jie²  Lamba, Bhumika²  Claridge-Chang, Adam^1,2,3 

[1] Duke NUS Med Sch, Program Neurosci & Behav Disorders, Singapore 138673, Singapore

[2] Agcy Sci Technol & Res, Inst Mol & Cell Biol, Singapore 138673, Singapore

[3] Natl Univ Singapore, Dept Physiol, Singapore 138673, Singapore

关键词: Anxiety;    Defense;    Behavior;    Rodent;    Stress;    Serotonin;    Meta-analysis;    Pain;    Isolation;    Receptor;    Transporter;    Corticotropin releasing hormone;   

DOI  :  10.1016/j.neubiorev.2016.04.011

来源: Elsevier

【 摘 要 】

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 over expression, pain, restraint, social isolation, corticotropin-releasing hormone and Crhr1 were selected for review. Eight interventions had statistically significant effects on rodent anxiety, while Htr1 a overexpression and Crh knockout did not. Evidence for publication bias was found in the diazepam, Htt knockout, and social isolation literatures. The Htr1 a 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. (C) 2016 The Authors. Published by Elsevier Ltd.

【 授权许可】

Free