CHRONIC ORTHOSTATIC AND ANTIORTHOSTATIC RESTRAINT INDUCE NEUROENDOCRINE, IMMUNE AND NEUROPHYSIOLOGICAL DISORDERS IN RATS

The tail-cast suspension rat model has been developed in ground labora tories interested in space physiology for extensive study of mechanism s causing the pathophysiological syndrome associated with space flight s, We used individually-caged male rats to explore the effects of acut e and chronic (7d) orthostatic restraint (OR) and head-down anti-ortho static restraint (AOR) on a series of physiological variables; The acu te restraint study showed that (1) the installation of the OR device i nduced an acute reaction for 2 days, with a substantial rise in ACTH ( x2) and CORT (x6), and that (2) the head-down tilt from OR to AOR indu ced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-ce rebro-ventricular pressure (Picv) monitored with an icy telemetric rec ording system, which receded to normal between 60 and 120 min; and (ii ) within 30 min a short-lived 4-fold rise in plasma ACTH and CORT leve ls, Chronic OR induced (1) the suppression of the diurnal ACTH/CORT rh ythm, with increased mean levels, especially for ACTH, (2) a degraded circadian locomotor activity rhythm manifested by a significant reduct ion in the spectral power of the 24h periodicity and a concomitant eme rgence of shorter (ultradian) periodicities, (3) an associated, but le ss pronounced alteration of the diurnal rhythm in body temperature; an d (4) a marked increase in baseline plasma levels of IL-1 beta and an increased reactivity in cytokine release following an E, coli endotoxi n (LPS) challenge. AOR induced (1) a similar obliteration of the circa dian ACTH/CORT rhythm, (2) the loss of close correlation between ACTH and CORT, (3) a generalized increase in baseline plasma IL-1 beta leve ls and (4) more extensive degradation of the circadian periodicity for both locomotor activity and, to a lesser extent, body temperature, re placed by dominant spectral powers for ultradian periodicities (3 to 1 0 h). In conclusion, both experimental paradigms - but AOR more than O R - caused a blockade of the circadian rhythmicity of major physiologi cal variables, the loss of normal correlations between ACTH and CORT, and inflammatory-immune hyperreactivity. These pathophysiological diso rders may all be parts of a complex chronic stress syndrome.