Selective Breeding for Divergence in Novelty-seeking Traits: Heritability and Enrichment in Spontaneous Anxiety-related Behaviors

Outbred Sprague–Dawley rats can be classified as high responders (HR) or low responders (LR) based on their levels of exploratory locomotion in a novel environment. While this novelty-seeking dimension was originally related to differential vulnerability to substance abuse, behavioral, neuroendocrine and gene expression studies suggest a fundamental difference in emotional reactivity between these animals. Here, we report the first study to selectively breed rats based on this novelty-seeking dimension. Response to novelty was clearly heritable, with a >2-fold difference in behavior seen after eight generations of selection. Three tests of anxiety-like behavior consistently showed significantly greater anxiety in LR-bred rats compared to HR-bred animals, and this difference was diminished in the open field test by administration of the anxiolytic benzodiazepine drug, chlordiazepoxide. Cross-fostering revealed that responses to novelty were largely unaffected by maternal interactions, though there was an effect on anxiety-like behavior. These selected lines will enable future research on the interplay of genetic, environmental and developmental variables in controlling drug seeking behavior, stress and emotional reactivity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42783/1/10519_2006_Article_9058.pd