Proceedings of The Physiological Society
University of Bristol (2005) J Physiol 567P, PC63
Stress responses of the HPA axis: relevance of time of day and basal pulsatility in male rats
Atkinson, Helen; Wood, Susan A; Bate, Elizabeth; Lightman, Stafford L;
1. HW LINE, University of Bristol, Bristol, United Kingdom.
Corticosterone (CORT) secretion in the rat is characterised by discrete pulses that vary in amplitude and frequency to produce a diurnal variation in circulating levels (Seale et al, 2004). Furthermore the phase of a pulse can influence the response of the hypothalamic-pituitary-adrenal (HPA) axis to a mild stress such as noise (Windle et al, 1998). This study examines the CORT response of male rats to noise stress at a time when there are no endogenous CORT pulses (early light phase) and when there are hourly CORT pulses (early dark phase). Male rats (14L:10D) were anesthetised and the jugular vein cannulated. Four days later cannulae were connected to an automated blood-sampling system (Windle et al, 1998; Seale et al, 2004). Blood samples were collected at 5 or 10 min intervals commencing at lights on or at lights off. Activation of a white noise generator in the room exposed all animals to 100 dB for 10 min. Animals remained in their home cages from the day of surgery and throughout blood-sampling. CORT levels were measured by radioimmunoassay. Animals were humanely killed at the end of the experiment. During the early light phase (morning), as expected, there was no evidence of endogenous CORT pulsatility. In response to the 10 min noise stress, CORT levels rose rapidly reaching peak values 5-10 min after the noise had ceased, thereafter CORT levels decreased logarithmically at a rate similar to that of the half-life of corticosterone (10 min). Application of a second noise 80 min later, resulted in a similar shape CORT response; however, the total response determined by AUC was significantly lower (82 ± 4%; mean ± sem; n=15; P<0.001; paired t test) than for the first noise exposure. During the early dark phase (evening), CORT pulses were observed prior to noise exposure. There was a clear response to the stress with CORT levels reaching a peak 5-10 min after the noise had ceased. In the evening, however, the decline in CORT levels only lasted 25-30 minutes before the resumption of pulsatility. Application of second noise, 80 min later, resulted in a similar CORT profile to the first noise exposure. Comparison of the AUCs revealed no evidence of adaptation (paired t test). Exposure to noise elicits a reproducible corticosterone profile. Repeating the stress results in adaptation in the morning but not in the evening. The brief secretory response to the stressor is followed by a falling phase that is similar to the hormones half-life, indicative of a lack of secretion during this time. In the evening these periods of HPA inactivity only last 25-30 min whereas in the morning the period of HPA inactivity is prolonged.
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