Differential sensitivity to dexamethasone suppression in an animal model of the DST.
The present study reports the feedback suppression of basal and stimulated corticosterone secretion in rats by low doses of dexamethasone (DEX). DEX suppression of basal secretion 6 hr after administration was observed with doses as low as 0.005 mg/kg. The lowest dose capable of suppressing basal corticosterone levels for 24 hr with a return to normal values by 36 hr was established to be 0.025 mg/kg. The ability of DEX to decrease corticosterone responses to physostigmine, morphine, immobilization, and ether stress was determined. Although the magnitude of the rise in corticosterone did not differ significantly among these evocative stimuli, the degree to which DEX attenuated these responses varied. The response to morphine was completely prevented by 0.025 mg/kg and the rises following ether or immobilization were decreased significantly. In contrast, the response to physostigmine was not affected by DEX. With a higher dose of DEX (0.25 mg/kg), responses to morphine, ether, and immobilization were completely eliminated, but the response to physostigmine was only attenuated partway. The time course of the suppression in basal levels, the attenuation of several stimuli for corticosterone secretion, and the "escape" of physostigmine-induced corticosterone secretion resemble the clinical Dexamethasone Suppression Test of endogenous depression and suggest that this test might be useful in the study of animal models of depression.
Lurie
S
S
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Kuhn
C
C
Bartolome
J
J
Schanberg
S
S
D000818:Animals; D003345:Corticosterone / Q000097:blood*; D003907:Dexamethasone; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006380:Helplessness, Learned / Q000523:psychology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D003907:Dexamethasone; D003345:Corticosterone