Effect of voluntary wheel running on circadian corticosterone release and on HPA axis responsiveness to restraint stress in Sprague-Dawley rats

Abstract

Adaptations of the hypothalamic-pituitary-adrenal (HPA) axis to voluntary exercise in rodents are not clear, because most investigations use forced-exercise protocols, which are associated with psychological stress. In the present study, we examined the effects of voluntary wheel running on the circadian corticosterone (Cort) rhythm as well as HPA axis responsiveness to, and recovery from, restraint stress. Male Sprague-Dawley rats were divided into exercise (E) and sedentary (S) groups, with E rats having 24-h access to running wheels for 5 wk. Circadian plasma Cort levels were measured at the end of each week, except for week 5 when rats were exposed to 20 min of restraint stress, followed by 95 min of recovery. Measurements of glucocorticoid receptor content in the hippocampus and anterior pituitary were performed using Western blotting at the termination of the restraint protocol. In week 1, circadian Cort levels were twofold higher in E compared with S animals, but the levels progressively decreased in the E group throughout the training protocol to reach similar values observed in S by week 4. During restraint stress and recovery, Cort values were similar between E and S, as was glucocorticoid receptor content in the hippocampus and pituitary gland after death. Compared with E, S animals had higher plasma ACTH levels during restraint. Taken together, these data indicate that 5 wk of wheel running are associated with normal circadian Cort activity and normal negative-feedback inhibition of the HPA axis, as well as with increased adrenal sensitivity to ACTH after restraint stress.

Voluntary wheel running initially increases adrenal sensitivity to adrenocorticotrophic hormone, which is attenuated with long-term training

“…lation surgery (P Ͻ 0.05), as has previously been reported (14). However, following surgery, all groups continued to gain weight as expected.…”

“…Thus, unlike with forced exercise, voluntary exercise may increase adrenal sensitivity to ACTH. In line with this hypothesis, we have previously shown that long-term wheel running (6 wk) in rats yields a normal GC response to restraint stress, despite attenuated ACTH levels (14). However, it is still unclear 1) if voluntary wheel running increases adrenal sensitivity to exogenous ACTH administration; 2) if the increased adrenal sensitivity to ACTH is sustained with prolonged training; and 3) how these apparent changes in adrenal sensitivity occur.…”

“…Cannulation surgeries were performed on either the day before the introduction to the running wheels (S2 and E2 rats) or after 6 wk of treatment (S8 and E8 rats), as previously described (14). Briefly, all animals had a microrenathane tube (MRE O40, 0.040 in.…”

“…On the 7th day (2-wk groups) or on the 49th day (8-wk groups), whole blood was sampled at 2100, 0300, and 1000 via a tail nick bleed to obtain diurnal plasma CORT concentrations, as described previously (14). During nighttime sampling (2100, 0300), the lights were kept off, and the only source of light was a battery-operated headlamp (white light).…”

“…One week following cannulation surgery, rats underwent a standardized 20-min restraint stress protocol at 0800, as previously described (14). During the restraint protocol, an initial blood sample was taken to establish baseline CORT and ACTH concentrations (time 0), after which the animal was placed in a clear, plastic, aerated restraint stress tube (Harvard Apparatus, Holliston, MA) for 20 min.…”