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

Abstract

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 i.v. 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.

Differential Impact of Audiogenic Stressors on Lewis and Fischer Rats: Behavioral, Neurochemical, and Endocrine Variations

“…This is concordant with earlier reports using female rats (Windle et al, 1998) and suggests that enhanced HPA reactivity of the Fischer rat (as compared to Lewis) is gender independent. While noise did not increase plasma corticosterone in Lewis rats in the present investigation, certain other stressors, including saline injection and restraint, have been reported to increase plasma corticosterone in both strains, although this effect was blunted and transient in the Lewis rats (Baumann et al, 2000;Stohr et al, 2000).…”

“…The observed behavioral response to noise exposure in the present study was very similar to that reported by Windle et al (1998) where female Fischer and Lewis rats displayed striking differences in their behavioral response to loud noise. We noted that, in general, the Fischer rats displayed a more active coping style (increased exploration and grooming), whereas the Lewis strain adopted a more defensive coping strategy (freezing).…”

“…In this regard, the strain differences reported here, as well as by others (Glowa et al, 1991;Gomez et al, 1998;Windle et al, 1998), may be reflective of strain differences in the number and/or sensitivity of pituitary corticotrophs to endogenous CRH and/or glucocorticoids, as suggested by in vitro findings in females of these strains (Zelazowski et al, 1992). Our results also make it tempting to suggest that noise exposure might have protracted effects on CRH changes related to the exposure environment and that Lewis rats might be more sensitive to these cues compared to Fischer rats.…”

“…The latter possibility is supported by the finding that the Fischer and Lewis rats show behavioral differences in response to centrally applied CRH (Glowa et al, 1991), such that exogenously administered CRH makes the Fischer rats behaviorally similar to non-CRH-exposed Lewis rats. Indeed, female Fischer rats show an immediate rise of plasma corticosterone following centrally applied CRH, compared to the relatively delayed increase observed in female Lewis rats (Windle et al, 1998). Likewise, it has been demonstrated that female Fischer rats are more sensitive to CRH-induced ACTH augmentation than Lewis rats (Spinedi et al, 1994).…”

“…Similarly, although efforts were made to minimize diurnal fluctuations of CRH by maintaining a narrow temporal testing window, this does not eliminate the potential peptidergic fluctuations that may occur within this time frame (Ixart et al, 1993). Likewise, Windle et al (1998) have recently demonstrated that the pulsatile release of plasma corticosterone is not only different between female Fischer and Lewis rats, but that noise exposure only evoked an increase in plasma corticosterone in the Lewis rats if the stressor coincided with the increasing phase of endogenous corticosterone release. In contrast, the Fischer rats responded with a surge of corticosterone irrespective of the directional phase of corticosterone at the time of noise exposure.…”