The cns site of glucocorticoid negative feedback during
lipopolysaccharide and psychological stress-induced fevers.
Morrow, Lee E., Jennifer L. McClellan, John J. Klir, Matthew J.
Kluger.
Department of Physiology, The University of Michigan Medical
School, Ann Arbor, MI 48109, College of Medicine, The University of
Iowa, Iowa City, IA 52242, Department of Physiology, Ohio State
University College of Medicine, Columbus, OH 43210, Institute for
Basic and Applied Medical Research, The Lovelace Institutes, 2425
Ridgecrest Dr. SE, Albequerque, NM 87108, Phone: 505 262-7531, FAX:
505 262-7043
APStracts 3:0153R, 1996.
The CNS Site of Glucocorticoid Negative Feedback During
Lipopolysaccharide and Psychological Stress-induced Fevers.
Glucocorticoids exert negative feedback in the anterior hypothalamus
(AH) during lipopolysaccharide (LPS)-induced fevers, but the central
location of their negative feedback during psychological stress
-induced fever has not been determined. To confirm that glucocorticoid
modulation of LPS fever occurs in the AH, adrenalectomized animals
were injected intrahypothalamically (ih) with either 0.25 ng of
corticosterone or vehicle followed by 50 [mu]g/kg LPS
intraperitoneally (ip). Animals pretreated with corticosterone
developed significantly smaller fevers (P = 0.007) than animals given
vehicle. To determine if glucocorticoid modulation during
psychological stress-induced fever may occur in the hippocampus, the
fornix was transected to block hippocampal communication with the AH.
This resulted in significantly larger psychological stress-induced
fevers (P = 0.02) compared to sham operated animals. There were no
differences between these groups for LPS-induced fevers (P = 0.92).
To determine where in the hippocampus glucocorticoids might exert
their negative feedback during psychological stress, rats were
microinjected with either 1 ng RU38486 (a type II glucocorticoid
receptor antagonist) or vehicle into the dentate gyrus prior to
exposure to the open-field. There were no differences between the
psychological stress-induced fevers of the RU38486 and vehicle
-injected groups, supporting the hypothesis that these fevers are
modulated elsewhere in the hippocampus. Our data support the
hypothesis that glucocorticoids modulate LPS-induced fever in the
anterior hypothalamus and do not involve the hippocampus, and that
psychological stress-induced fevers are modulated by neural
connections between the hippocampus and the hypothalamus. The precise
sites of action of glucocorticoid negative feedback on stress-induced
fevers in the hippocampus (or other brain regions) is not yet known.
Received 1 June 1995; accepted in final form 8 April 1996.
APS Manuscript Number R330-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96