Abstract
Metabolic function is integrally related to an individual's susceptibility to, and progression of, disease. Selective breeding for intrinsic treadmill running in rats has produced distinct lines of high- or low-capacity runners (HCR and LCR, respectively) that exhibit numerous physiological differences. To date, the role of intrinsic aerobic capacity on behavior and stress response in these rats has not been addressed and was the focus of these studies. HCR and LCR rats did not differ in their locomotor response to novelty or behavior in the light/dark box. In contrast, immobility in the forced swim test was higher in LCR rats compared with HCR rats, regardless of desipramine treatment. Although both HCR and LCR rats responded to cat odor with decreased exploration and increased risk assessment, HCR rats showed greater contextual conditioning to cat odor. HCR rats exhibited higher expression of corticotropin-releasing hormone in the central nucleus of the amygdala, as well as heavier adrenal and thymus weight. Corticosterone was comparable among HCR and LCR rats at light/dark transitions, and in response to unavoidable cat odor. HCR rats, however, exhibited a greater corticosterone response following the light/dark box. These experiments show that the LCR phenotype associates with decreased risk assessment in response to salient danger signals and passive coping. In contrast, HCR rats show a more naturalistic strategy in that they employ active coping and a more vigilant and cautious response to environmental novelty and salient danger signals. Within this context, we propose that intrinsic aerobic capacity is a central feature mechanistically linking complex metabolic disease and behavior.
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Acknowledgements
This work was supported by NIH Grants No. P01 DA021633 to HA, No. 5T32HD007422-18, and No. UL1RR024986, and the Office of Naval Research Grant No. N00014-09-1-0598 to HA. The LCR and HCR rat resource was supported by Award R24RR017718 to SLB and LGK from the National Center for Research Resources (a component of the National Institutes of Health). We acknowledge the expert care of the rat colony provided by Molly Kalahar and Lori Gilligan.
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Burghardt, P., Flagel, S., Burghardt, K. et al. Risk-assessment and Coping Strategies Segregate with Divergent Intrinsic Aerobic Capacity in Rats. Neuropsychopharmacol 36, 390–401 (2011). https://doi.org/10.1038/npp.2010.144
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DOI: https://doi.org/10.1038/npp.2010.144
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