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The Pulsatile Characteristics of Hypothalamo-Pituitary-Adrenal Activity in Female Lewis and Fischer 344 Rats and Its Relationship to Differential Stress Responses¹

Neuroendocrine Research Group, Department of Anatomy, School of Medical Sciences (R.J.W., S.A.W., C.D.I.), Bristol, United Kingdom BS8 1TD; and the Department of Medicine, University of Bristol, Bristol Royal Infirmary (R.J.W., S.A.W., S.L.L.), Bristol, United Kingdom BS2 8HW

Address all correspondence and requests for reprints to: Dr. Richard Windle, Department of Anatomy, School of Medical Sciences, University of Bristol, University Walk, Bristol, United Kingdom BS8 1TD. E-mail: r.j.windle{at}bris.ac.uk

The dynamic patterns of basal and stimulated hypothalamo-pituitary-adrenal (HPA) activity of freely moving female Lewis and Fischer 344 rats were compared using an automated blood-sampling system. Both strains showed pulsatile corticosterone release throughout the 24 h cycle. Lewis rats showed clear circadian variation in both pulse frequency (8.4 ± 0.4 pulses between 1700–2300 h vs. 5.3 ± 0.8 pulses between 0500–1100 h; P < 0.05) and height (198 ± 27 ng/ml between 1700–2300 h vs. 107 ± 14 ng/ml between 0500–1100 h; P < 0.05). Fischer rats exhibited pulses of similar frequency and height to those in Lewis rats during the evening, but showed no circadian variation, resulting in higher mean daily corticosterone concentrations. Although both strains showed behavioral and HPA responses to white noise stress (10 min; 114 dB), Fischer rats showed much greater increases in total activity, grooming, and rearings, and two important differences in the corticosterone responses were observed. First, in Lewis rats a clear relationship existed between basal and stimulated HPA activities, in that a significant response was seen only when the stress coincided with the rising (secretory active) phase of a basal pulse. Noise stress coinciding with a falling (nonsecretory) phase elicited no significant response. In contrast, Fischer rats showed similar responses regardless of the underlying pulse phase. Second, after the peak response at 20 min (Lewis, 237 ± 67 ng/ml; Fischer, 390 ± 57 ng/ml), corticosterone levels fell rapidly in Lewis rats, but remained maximally elevated for 20 min in Fischer rats, resulting in a significantly greater integrated response. The corticosterone response to iv CRF was unaffected by pulse phase in both strains, suggesting that a suprapituitary mechanism mediates the phase-dependent response to stress in the Lewis strain. CRF-induced corticosterone levels rose more rapidly in Fischer rats, peaking at 10 min (473 ± 95 ng/ml) compared with 30 min (390 ± 75 ng/ml) in Lewis rats, suggesting greater pituitary sensitivity in this strain. Thus, differences in both central and pituitary control of the HPA axis contribute to the strain difference in stress responsiveness between female Lewis and Fischer rats.

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