Induction of a Catabolic State in Rats by Dexamethasone: Dose or Time Dependency?

Abstract

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 G ₉ received 1.50 mg/kg/d of DEX by intraperitoneal (IP) injection for 3, 5, 7, or 9 days, respectively. Groups G_3PF, G_5PF, G_7PF, or G_9PF were pair-fed to groups G₃, G₅, G7, or Gg, 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 G_0.75, G_1.50, and G_2.50 received 0.75, 1.50, and 2.50 mg/kg/d, respectively, of DEX by IP injection for 5 days. Group PF was pair-fed to group G_2.50 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. (Journal of Parenteral and Enteral Nutrition 24:30-36, 2000)