Neurotoxic Effect of Dexamethasone: Weakening upon the Action of Antidepressants

Abstract

Dose-dependent neurotoxic effects (decrease in the amplitude of field potentials generated by neurons of the СА1 area, dentate gyrus, and dorsal striatum, but not by neurons of layers ІІ and ІІІ of the parietal cortex, recorded in slices of the rat brain) were observed 24 h after i.p. injection оf dexamethasone in doses of 7 and 20 mg/kg. Dexamethasone-induced decreases in the reactivity of glutamatergic synapses in the studied cerebral structures were weakened by a noncompetitive blocker of NMDA receptors, ketamine (30 mg/kg), and an inhibitor of tyrosine protein phosphatases, sodium vanadate (15 mg/kg), if the latter agent was injected 6 h after dexamethasone administration. The neurotoxic effect of dexamethasone was intensified by a coagonist of NMDA receptors, glycine (50 mg/kg), as well as in the case where injections of dexamethasone were combined with single injections of the antidepressant fluoxetine (20 mg/kg) but not when another antidepressant, pyrazidol, was injected in the same dose. Chronic (two weeks) injections of fluoxetine and pyrazidol weakened manifestations of dexamethasone neurotoxicity. On-regulation of NMDA receptors and suppression of expression of neurotrophins are considered probable mechanisms underlying neurotoxicity of this hormone. The effect of chronic injections of antidepressants on the respective processes is discussed.

Adrenergic receptors blockade alleviates dexamethasone-induced neurotoxicity in adult male Wistar rats: Distinct effects on β-arrestin2 expression and molecular markers of neural injury

“…In accordance with previous findings [ 30 – 32 ], the present study showed that dexamethasone injection for 7 days slightly reduced brain weight and survival rate compared to control group. Also, histopathological examination of the cerebral cortex using H&E and Nissl stains showed marked degeneration in the cortical neurons and disruption of its integrity.…”

“…Dexamethasone neurotoxicity has been reported in several previous experimental and clinical studies [ 30 – 32 ]. Intraperitoneal injection of either 7 or 20 mg/kg dexamethasone caused neurotoxicity in the cerebral cortex after 24 hours by increasing the activity of N-methyl D-aspartate (NMDA) receptors and suppression of neurotrophins [ 30 ].…”

“…Dexamethasone neurotoxicity has been reported in several previous experimental and clinical studies [ 30 – 32 ]. Intraperitoneal injection of either 7 or 20 mg/kg dexamethasone caused neurotoxicity in the cerebral cortex after 24 hours by increasing the activity of N-methyl D-aspartate (NMDA) receptors and suppression of neurotrophins [ 30 ]. In addition, low dose dexamethasone (0.2 mg/kg) acutely induced c-Fos expression in the hippocampus of neonatal rats and increased apoptotic marker expression specifically in the subiculum [ 31 ].…”

Effects of Chronic Introduction of Antidepressants on NMDA-Induced Damage to Neurons of the Rat Hippocampus and Cerebral Cortex

“…The technique was described in detail earlier [14]. Briefly, the rats were decapitated under ketamine anesthesia (50 mg/kg, i.p.).…”