Environmental enrichment differentially suppresses anxiety-related behaviors, reduces passive avoidance learning, and...

Anxiety disorder risk is influenced by both adverse environmental factors and genetic background. We previously described high-avoidance animal (HAA) and low-avoidance animal (LAA) strains of male Hatano rats that may provide robust models for assessing interactions between genetic background and environment driving anxiety disorder pathogenesis. We examined the potential of environmental enrichment (EE), a non-pharmacological approach, to suppress trait anxiety disorders by comparing anxiety-related behaviors and physiological metrics between HAA and LAA lines exposed to EE or standard housing. At 4 weeks of age, 10-12 male rats from each strain were assigned to EE or standard conditions. EE for 4-5 weeks significantly (p = 0.0002 by Tukey-Kramer's test) reduced anxiety-related behaviors in LAAs in the elevated plus maze test, but had no similar anxiolytic effect in HAAs. In contrast, EE for 11 weeks significantly (p = 0.0072 by Tukey-Kramer's test) reduced passive avoidance memory retention in HAAs, but not in LAAs. Real-time quantitative PCR revealed upregulated expression of Bdnf exons 1, 3, and 4 in the hippocampus of LAAs following EE, while the same treatment increased the expression of Bdnf exon 3 in the hippocampus of HAAs. Alternatively, EE did not alter mRNA expression levels of the BDNF receptor TrkB and the glucocorticoid receptor in hippocampus, or influence plasma corticosterone, prolactin, and testosterone concentrations. These findings have potential clinical implications for anxiety disorders, suggesting that effects of EE may vary depending on an individual's genetic background and underlying biological characteristics.