Baseline and Stress‐Induced Plasma Corticosterone Concentrations of Mice Selectively Bred for High Voluntary Wheel Running

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis is important in regulating energy metabolism and in mediating responses to stressors, including increasing energy availability during physical exercise. In addition, glucocorticoids act directly on the central nervous system and influence behavior, including locomotor activity. To explore potential changes in the HPA axis as animals evolve higher voluntary activity levels, we characterized plasma corticosterone (CORT) concentrations and adrenal mass in four replicate lines of house mice that had been selectively bred for high voluntary wheel running (HR lines) for 34 generations and in four nonselected control (C) lines. We determined CORT concentrations under baseline conditions and immediately after exposure to a novel stressor (40 min of physical restraint) in mice that were housed without access to wheels. Resting daytime CORT concentrations were approximately twice as high in HR as in C mice for both sexes. Physical restraint increased CORT to similar concentrations in HR and C mice; consequently, the proportional response to restraint was smaller in HR than in C animals. Adrenal mass did not significantly differ between HR and C mice. Females had significantly higher baseline and postrestraint CORT concentrations and significantly larger adrenal glands than males in both HR and C lines. Replicate lines showed significant variation in body mass, length, baseline CORT concentrations, and postrestraint CORT concentrations in one or both sexes. Among lines, both body mass and length were significantly negatively correlated with baseline CORT concentrations, suggesting that CORT suppresses growth. Our results suggest that selection for increased locomotor activity has caused correlated changes in the HPA axis, resulting in higher baseline CORT concentrations and, possibly, reduced stress responsiveness and a lower growth rate.

Acute stress-induced changes in hormone and lipid levels in mouse plasma

“…To undertake the present study, we first measured the concentrations of selected hormones and plasma lipids in a normal (unstressed) mouse group (Table 1). While the values showed significant individual differences, overall levels were consistent with previous results (Malisch et al 2007;Fuchsl et al 2013).…”

Erythropoietin elevates but not voluntary wheel running in mice

“…For each of the two samples, approximately 75l of blood was obtained through retroorbital sinus puncture (Hoff, 2000;Malisch et al, 2007) using heparinized microhematocrit tubes (Fisher Scientific, Pittsburgh, PA, USA). This original sample was split into two duplicate 20l samples in precalibrated microhematocrit tubes (Drummond Scientific Company, Broomall, PA, USA).…”

Within-lifetime trade-offs but evolutionary freedom for hormonal and immunological traits: evidence from mice bred for high voluntary exercise

“…Mice from the four replicate HR lines run 2.5-3.0 times more revolutions per day than those from four non-selected control (C) lines when given access to wheels (Garland et al, 2011a). In addition, these HR mice evolved baseline levels of circulating CORT that are approximately twice those of C mice (Malisch et al, 2007;Malisch et al, 2008).…”

“…The elevated baseline CORT levels in HR mice potentially increase energy availability during exercise, and hence could be an adaptation (Malisch et al, 2007;Malisch et al, 2008), but the high CORT could also result in a chronic suppression of the inflammatory response (Malisch et al, 2009b), which could be viewed as a cost or trade-off.…”

“…We quantified sickness behavior in two complementary ways: an observational behavioral assay (Table1) and subsequent voluntary wheel running. We also quantified CORT levels in a later generation of mice to ensure that they were still higher in HR than in C mice, as expected from previous studies Malisch et al, 2007;Malisch et al, 2008).…”