Effects of Long-Term Voluntary Exercise on the Mouse Hypothalamic-Pituitary-Adrenocortical Axis

Abstract

We studied the effects of long-term (i.e. 4 wk) voluntary exercise on the hypothalamic-pituitary-adrenocortical (HPA) axis in male mice. Voluntary exercise was provided by giving mice access to a running wheel, in which they indeed ran for about 4 km/d. Exercising mice showed similar body weights as control animals but presented less abdominal fat, lighter thymuses, and heavier adrenal glands. Exercise resulted in asymmetric structural changes in the adrenal glands. Whereas control mice had larger left than right adrenals, this condition was abolished in exercising animals, mainly because of enlargement of the right adrenal cortex. Tyrosine hydroxylase mRNA expression in the adrenal medullas of exercising mice was increased. In exercising mice, early-morning baseline plasma ACTH levels were decreased, whereas plasma corticosterone levels at the start of the dark phase were twice as high as those in control animals. To forced swimming and restraint stress, exercising mice responded with higher corticosterone levels than those of the control animals but with similar ACTH levels. However, if exposed to a novel environment, then exercising mice presented decreased ACTH responses. Interestingly, exercising mice showed a decreased corticosterone response to novelty only when the novel environment contained a functioning running wheel. Glucocorticoid receptor levels were unchanged, whereas mineralocorticoid receptor levels were decreased, in hippocampus of exercising animals. Corticotropin-releasing factor mRNA levels in the paraventricular nucleus were lower in exercising mice. Thus, voluntary exercise results in complex, adaptive changes at various levels within the HPA axis as well as in sympathoadrenomedullary and limbic/neocortical afferent control mechanisms. These changes seem to underlie the differential responsiveness of the HPA axis to physical vs. emotional challenges.

Corticosterone and dopamine D2/D3 receptors mediate the motivation for voluntary wheel running in C57BL/6J mice

“…The moderate and short-lasting effects of mifepristone on voluntary running activity suggest that motivating effects may possibly be initiated via a GR-dependent mechanism, but not their persistence. This is in agreement with the observation that GR levels were found to be unaltered by 4 weeks of voluntary wheel running, despite a downregulation of the high affinity mineralocorticoid receptors [13] which may thus contribute more to motivation to exercise than GRs.…”

“…Forced exercise has a stressful component that may contribute to its effects on the brain [11]. Although less stressful than forced exercise [11], voluntary wheel running also activates the hypothalamic pituitary adrenocortical (HPA) axis and elevates plasma levels of the stress hormone corticosterone [12,13]. Interestingly, corticosterone, when induced or administered at sufficient levels, has direct reinforcing and rewarding properties and enhances reinforcing and rewarding effects of abused drugs via activation of the low affinity glucocorticoid receptor (GR) [14][15][16][17][18].…”

Using eye temperature and heart rate for stress assessment in young horses competing in jumping competitions and its possible influence on sport performance

“…However, short, intense stressor(s) can also compromise animal well-being and induce distress as a response to acute stress (Moberg, 2000). In fact, despite the fact that most acute stress responses (like the 'flight or fight response') seem to be beneficial and desirable for the animal (as they promote a physical and physiological adaptation to the environment), some naturally rewarding behaviours, such as exercise, can also induce an acute stress response in a very similar profile to that which produces distress (Droste et al, 2003). As regards horses, different studies have reported either negative or positive physical and physiological effects due to an acute stress response during exercise (Langsetmo et al, 2000;Moberg, 2000).…”

Effects of genetic background and environmental novelty on wheel running as a rewarding behaviour in mice

“…Alternatively, an explanation might be found in one of the properties of wheel running. Voluntary wheel running causes an increase in plasma corticosterone levels in female house mice [11] and male C57 mice [9]. We performed a pilot study aimed at investigating the relation between wheel running and corticosterone in DBA and C57 mice and found that already after 90 min of wheel exposure there was an increase in plasma corticosterone.…”