title: Chronic orthostatic and antiorthostatic restraint induce neuroendocrine, immune and neurophysiologial disorders in rats.
abstract: The tail-cast suspension rat model has been developed in ground laboratories interested in space physiology for extensive study of mechanisms causing the pathophysiological syndrome associated with space flights. We used individually-caged male rats to explore the effects of acute and chronic (7d) orthostatic restraint (OR) and head-down anti-orthostatic restraint (AOR) on a series of physiological variables. The acute restraint study showed that (1) the installation of the OR device induced 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 induced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-cerebro-ventricular pressure (Picv) monitored with an icv telemetric recording 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 levels. Chronic OR induced (1) the suppression of the diurnal ACTH/CORT rhythm, with increased mean levels, especially for ACTH, (2) a degraded circadian locomotor activity rhythm manifested by a significant reduction in the spectral power of the 24h periodicity and a concomitant emergence of shorter (ultradian) periodicities, (3) an associated, but less pronounced alteration of the diurnal rhythm in body temperature; and (4) a marked increase in baseline plasma levels of IL-1 beta and an increased reactivity in cytokine release following an E. coli endotoxin (LPS) challenge. AOR induced (1) a similar obliteration of the circadian ACTH/CORT rhythm, (2) the loss of close correlation between ACTH and CORT, (3) a generalized increase in baseline plasma IL-1 beta levels and (4) more extensive degradation of the circadian periodicity for both locomotor activity and, to a lesser extent, body temperature, replaced by dominant spectral powers for ultradian periodicities (3 to 10h). In conclusion, both experimental paradigms--but AOR more than OR--caused a blockade of the circadian rhythmicity of major physiological variables, the loss of normal correlations between ACTH and CORT, and inflammatory-immune hyperreactivity. These pathophysiological disorders may all be parts of a complex chronic stress syndrome.
authors.affiliation: Department of Health Sciences and Membrane Interactions, University of Montpellier-2, France.
authors.forename: I
authors.initials: I
authors.lastname: Assenmacher
authors.forename: M
authors.initials: M
authors.lastname: Mekaouche
authors.forename: D
authors.initials: D
authors.lastname: Maurel
authors.forename: G
authors.initials: G
authors.lastname: Barbanel
authors.forename: L
authors.initials: L
authors.lastname: Givalois
authors.forename: J
authors.initials: J
authors.lastname: Boissin
authors.forename: F
authors.initials: F
authors.lastname: Malaval
authors.forename: G
authors.initials: G
authors.lastname: Ixart
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001831:Body Temperature; D002552:Cerebral Ventricles / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism*; D018475:Head-Down Tilt / Q000009:adverse effects / Q000502:physiology*; D019417:Hindlimb Suspension / Q000009:adverse effects / Q000502:physiology*; D007375:Interleukin-1 / Q000378:metabolism; D007427:Intracranial Pressure; D008297:Male; D009043:Motor Activity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000209:etiology* / Q000378:metabolism; D018474:Weightlessness Simulation
chemical_list: D007375:Interleukin-1; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone