Jun 23, 2016

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

Neuroscience and Biobehavioral Reviews
Farhan MohammadAdam Claridge-Chang

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.

  • References299
  • Citations13

Mentioned in this Paper

Study
Nervousness
Serotonin Reuptake Inhibitor [EPC]
Meta-Analysis (Publications)
Meta Analysis (Statistical Procedure)
CRHR1 gene
Genes
Receptors, Corticotropin-Releasing Hormone
CRHR1
Serotonin Measurement

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