TY - JOUR T1 - Anxiety-related interventions in rodent defense behaviors: systematic review and meta-analyses JF - bioRxiv DO - 10.1101/020701 SP - 020701 AU - Farhan Mohammad AU - Joses Ho AU - Chun Lei Lim AU - Jia Hern Woo AU - Dennis Jun Jie Poon AU - Bhumika Lamba AU - Adam Claridge-Chang Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/12/18/020701.abstract N2 - Rodent defense behavior assays have been widely used as preclinical models of anxiety to study possible 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 performed 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. ER -