Abstract
Chronic stress and extended periods of elevated circulating glucocorticoids have been reported to exacerbate excitotoxicity-induced hippocampal neuronal injury in rat. Despite continued interest in the effects of protracted exposure to stress or glucocorticoids, there has been little examination of how other types of neurotoxicity may be exacerbated or blocked, by stress. Here we examined the effects of chronic supraphysiologic levels of corticosterone on D-3,4-methylenedioxymethamphetamine (D-MDMA)-induced striatal dopaminergic neurotoxicity in the female C57BL/6J mouse. Corticosterone (5 mg, 15 mg or placebo) pellets were implanted to continuously elevate circulating glucocorticoids and create a model of the ultimate effect of chronic activation of the hypothalamic-pituitary-adrenal axis. After 7 days, a neurotoxic regimen of D-MDMA was administered (20 mg/kg s.c. every 2 hx4); thymus, spleen, striatum and hippocampus were collected 72 h later. Significant involution of thymus and spleen confirmed the bioavailability of the corticosterone at both dosages. D-MDMA increased the striatal levels of the astrocyte-localized protein glial fibrillary acidic protein (GFAP, a marker of gliosis); both dosages of corticosterone exacerbat...Continue Reading
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