Pathological effects of MK-801 in the rat posterior cingulate/retrosplenial cortex.
Many N-methyl-D-aspartate (NMDA) antagonists cause vacuolization and necrosis in the posterior cingulate/retrosplenial (PC/RS) cortex of rats after single-dose administration. This article reviews a series of investigational studies that have characterized this effect. All the studies have used single doses of MK-801 in rats. Techniques employed were light microscopy, transmission electron microscopy, quantitative enzyme-linked immunosorbent assay (ELISA), and cell counting. Our studies demonstrated: (1) formation of vacuoles within 30 minutes of treatment, (2) dose-dependent necrosis of susceptible PC/RS neurons, (3) increased glial fibrillary acidic protein in response to neuronal necrosis, (4) significantly greater necrosis in female than in male rats, and (5) increases in necrosis along a rostrocaudal gradient within the PC/RS cortex. In addition, these studies illustrate a number of variables that impact the expression and detection of neuronal vacuolization and necrosis in rats after treatment with MK-801.
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Eli Lilly and Company, Greenfield, IN, USA.
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced* / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D016291:Dizocilpine Maleate / Q000633:toxicity*; D005260:Female; D008297:Male; D051381:Rats
D016291:Dizocilpine Maleate