QUANTITATIVE-ANALYSIS OF FACTORS INFLUENCING NEURONAL NECROSIS INDUCED BY MK-801 IN THE RAT POSTERIOR CINGULATE RETROSPLENIAL CORTEX

A single dose of the non-competitive NMDA receptor antagonist MK-801 ( dizocilpine maleate) induces neuronal necrosis in the posterior cingul ate/retrosplenial (PC/RS) cortex of adult rats. The present studies fu rther characterized this effect and evaluated several variables that a ffect its expression. Male and female rats of two strains (Sprague-Daw ley and Fischer 344) and two ages (70 and 127 days) were given a singl e subcutaneous injection of vehicle (water) or MK-801 (0.5, 1.0 or 5.0 mg/kg). A simple behavioral response (recumbency) and number of necro tic neurons in the PC/RS cortex were evaluated. MK-801 induced dose-de pendent recumbency which was more severe and of longer duration in fem ales of either strain or age. Tn addition, female rats (regardless of strain, dose, or age) consistently had significantly more necrotic PC/ RS neurons than male rats. In a second study, a high dose of MK-801 wa s given intraperitoneally (10 mg/kg) to male and female Sprague-Dawley rats (90-120 days of age). Necrotic neuron counts were determined at 5 separate rostrocaudal levels of the PC/RS cortex. At levels where ne uronal necrosis occurred, the magnitude of the effect was significantl y greater in females than males and the number of necrotic neurons inc reased along a rostral to caudal gradient. Our findings indicate that (1) MK-801 dose dependently induces recumbency and necrosis of PC/RS c ortical neurons in both Sprague-Dawley and Fischer 344 rats, (2) femal e rats of either strain are more sensitive than their male counterpart s, and (3) the extent of necrosis of PC/RS cortical neurons increases along a rostral to caudal gradient.