Rat models for low and high adaptive response to exercise differ for stress‐related memory and anxiety

Physical exercise and fitness may serve as resilience factors to stress exposure. However, the extreme range in human exercise performance suggests that genetic variation for exercise capacity could be a confounding feature to understanding the connection between exercise and stress exposure. To test this idea, we use laboratory rat models selectively bred for a low and high gain in aerobic running capacity in response to training to examine whether an inherent capacity to respond to physical exercise reflects how stress changes neurobiological functioning and regulates fear‐associated memory processing. Utilization of this contrasting rat model system of low and high responders has the potential to guide the interpretation of the reported association with exercise involvement and the reduction of stress‐induced anxiety disorders. Our data show that aerobic fitness may be linked to the ability to regulate fear‐associated memories. We also show that acquired exercise capacity may play a key role in regulating responses to an acute stressor. Exercise sensitivity plays a significant role in the activation of the plasticity‐associated molecule extracellular signal‐regulated kinase, changes in stress hormone activity, and anatomical modifications to the noradrenergic locus coeruleus. These data identify a unique operational mechanism that may serve as translational targets for lessening symptoms of stress and anxiety.