Blockage of glucocorticoid, but not mineralocorticoid receptors prevents the persistent increase in circulating basal corticosterone concentrations following stress in the rat.
Exposure to a single session of intense inescapable stressors results in elevations of plasma corticosterone levels selective to the trough of the circadian rhythm that last for several days after stressor cessation. In the present study, we examined whether this stress-induced alteration in the regulation of the circadian trough is dependent upon glucocorticoid and/or mineralocorticoid receptor activation during stress. Pre-treatment with the mineralocorticoid receptor (MR) antagonist, spironolactone (RU-28318; 50 mg/kg, s.c.), and/or the glucocorticoid receptor (GR) antagonist, mifepristone (RU-38486; 50 mg/kg, s.c.) 1 h before inescapable stress (40, 2.0-mA tail-shocks delivered over a 1 h period) had no effect on the acute plasma corticosterone response to inescapable stress. Treatment with the MR antagonist alone did not affect the appearance of basal corticosterone elevations in stressed rats. However, the elevated trough plasma corticosterone levels were no longer evident in rats treated previously with the GR antagonist either alone or in combination with the MR antagonist. GR activation during stressor exposure appears to be necessary for the development of subsequent basal corticosterone elevations.
Moldow
R L
RL
Neurobehavioral Research Laboratory, Department of Veterans Affairs Medical Center, 385 Tremont Avenue, East Orange, NJ 07018-1095, USA. moldow@njneuromed.org
Beck
K D
KD
Weaver
S
S
Servatius
R J
RJ
D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects; D003345:Corticosterone / Q000097:blood*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D000451:Mineralocorticoid Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology*; D013312:Stress, Physiological / Q000378:metabolism*
D000451:Mineralocorticoid Receptor Antagonists; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D015735:Mifepristone; D003345:Corticosterone