Induction of a catabolic state in rats by dexamethasone: dose or time dependency?
BACKGROUND
Daily injections of dexamethasone (DEX) given to adult rats are a recognized but nonstandardized model of stress. The aim of this work was to establish a reproducible and accurate model of stress in adult rats by chronic injection of DEX in order to standardize it. For this purpose, the effect of the duration of treatment and the effect of DEX dose were tested. To help understand the mechanisms of the catabolic effect of DEX, the study was extended to the metabolism of glutamine (GLN). In experiment 1, 60 male Sprague-Dawley rats (3 months old) were divided into 8 groups of 6 rats: groups G3, G5, G7, and G9 received 1.50 mg/kg/d of DEX by intraperitoneal (i.p.) injection for 3, 5, 7, or 9 days, respectively. Groups G3PF, G5PF, G7PF, or G9PF were pair-fed to groups G3, G5, G7, or G9, respectively. Group AL (n = 12) was healthy rats fed ad libitum.


RESULTS
In treated rats, nitrogen balance reached its lowest value at day 5. After 9 days treatment by DEX, the catabolic state was reduced. An increase in GLN-synthetase activity and a decrease in muscle GLN content were related to DEX per se not to DEX-induced anorexia. In experiment 2, 25 rats were divided into 5 groups of 5 animals. Groups G0.75, G1.50, and G2.50 received 0.75, 1.50, and 2.50 mg/kg/d, respectively, of DEX by i.p. injection for 5 days. Group PF was pair-fed to group G2.50 and group AL was control rats.


RESULTS
DEX induced a decrease in nitrogen balance that was dose-independent. GLN-synthetase activity was increased maximally in gastrocnemius by 0.75 mg/kg.


CONCLUSIONS
Five days of treatment by DEX and a dose of 0.75 mg/kg/d induced a marked catabolic state.
Minet-Quinard
R
R
Department of Biochemistry, Molecular Biology, and Nutrition, Pharmacy School, Clermont Ferrand, France.
Moinard
C
C
Walrand
S
S
Villié
F
F
Normand
B
B
Vasson
M P
MP
Chopineau
J
J
Cynober
L
L
D000818:Animals; D001835:Body Weight; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000494:pharmacology; D005973:Glutamine / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005938:Glucocorticoids; D009124:Muscle Proteins; D005973:Glutamine; D003907:Dexamethasone