Recovery from disrupted ultradian glucocorticoid rhythmicity reveals a dissociation between hormonal and behavioral stress responsiveness

Publication Type:

Journal Article


J Neuroendocrinol, Volume 22, Number 8, p.862-871 (2010)

DOI Name (links to online publication)



Affect; Animal; Animals; AXIS; blood; Corticosterone; Disease; glucocorticoid; Glucocorticoids; Health; Homeostasis; HORMONE; HPA; HPA axis; HPA-axis; Locomotion; Male; MALE-RATS; Netherlands; pharmacology; RAT; Rats; RELEASE; Research; RESPONSIVENESS; se


Abstract Ultradian release of glucocorticoids is thought to be essential for homeostasis and health. Deviation from this pulsatile release pattern is considered to compromise resilience to stress-related disease, even after hormone levels have normalised. Here, we investigate how constant exposure to different concentrations of corticosterone affects diurnal and ultradian pulsatility. The rate of recovery in pulsatile HPA activity after withdrawal of exogenous corticosterone is also examined. Finally, the behavioural and neuroendocrine responsiveness to an audiogenic stressor is studied. Adrenally intact male rats were subcutaneously implanted with vehicle, 40% or 100% corticosterone pellets for 7 days. The continuous release of corticosterone from these implants abolished diurnal and ultradian corticosterone variation as measured with high frequency automated blood sampling. Pellet removal on post-surgery day 8 allowed rapid recovery of endogenous rhythms in animals previously exposed to daily average concentrations (40%) but not after exposure to high concentrations (100%) of corticosterone. Behavioural and neuroendocrine responsiveness to stress was distinctly different between the treatment groups. Audiogenic stimulation one day after pellet removal resulted in a similar corticosterone response in animals previously exposed to 40% corticosterone or vehicle. The 40% pellet group showed, however, less and shorter behavioural activity (i.e. locomotion, risk assessment) to noise stress as compared to 100% corticosterone and vehicle treated animals. In conclusion, unlike the animals impanted with 100% corticosterone, we find that basal HPA axis activity in the 40% group which had mean daily levels of circulating corticosterone in the physiological range, rapidly reverts to the characteristic pulsatile pattern of corticosterone secretion. Upon reinstatement of the ultradian rhythm, despite the fact that these animals did not differ from controls in their response to noise stress, they did show substantial changes in their behavioural response to stress