Dexamethasone changes brain monoamine metabolism and aggravates ischemic neuronal damage in rats

Background: Glucocorticoids have been reported to aggravate ischemic brain damage. Because changes in the activities of various neuronal systems are c losely related to the outcome of ischemic damage, the authors evaluated the effects of dexamethasone on the monoaminergic systems and ischemic neurona l damage. Methods: The right middle cerebral artery was occluded for 2 h, and the tis sue concentrations of monoamines and their metabolites were determined in t he cerebral cortex and the striatum of rats. The turnover of 5-hydroxytrypt amine was compared in animals injected with saline and those injected with dexamethasone twice (2 mg/kg in each injection) by evaluating the probeneci d-induced accumulation of 5-hydroxyindoleacetic acid. The turnovers of nore pinephrine and dopamine were estimated from the alpha-methyl-p-tyrosine-ind uced depletion of norepinephrine and dopamine, respectively. The effect of dexamethasone on the infarct volume was evaluated by triphenyltetrazolium c hloride stain in rats subjected to 2 h of occlusion. Results: Dexamethasone did not affect the cortical 5-hydroxytryptamine or 5 -hydroxyindoleacetic acid contents. However, it suppressed the turnover of the cortical 5-hydroxytryptamine on both sides. Dexamethasone reduced the t urnover of the striatal 5-hydroxytryptamine and facilitated the dopamine tu rnover. In rats subjected to 2 h of occlusion and 2 h of reperfusion, the i nfarct volume was 10.5 times greater in the group that received dexamethaso ne than in the animals that received saline. Conclusions: Dexamethasone suppresses the inhibitory serotonergic system an d facilitates the excitatory dopaminergic system in the rat telencephalon. This may be a mechanism by which dexamethasone aggravates ischemic neuronal injury.