MK-801 NEUROTOXICITY IN THE GUINEA-PIG CEREBRAL-CORTEX - SUSCEPTIBILITY AND REGIONAL DIFFERENCES COMPARED WITH THE RAT

N-methyl-D-aspartate (NMDA) receptor antagonists induce transient vacu ole formation in neurons of the retrosplenial cortex and, after higher doses, necrosis in the same region, To our knowledge, all studies dem onstrating these effects have been carried out in rats or mice. The pr esent study investigated whether vacuolization occurs in the guinea pi g, rats being used as controls, Female Dunkin-Hartley guinea pigs (age 15-18 weeks) were given a single subcutaneous injection of saline or the non-competitive NMDA antagonist dizocilpine maleate [(+)-MK-801; 1 , 4, or 12 mg/kg]. Female Sprague-Dawley rats (age 16 weeks) received saline or MK-801 (1 mg/kg), Whatever the dose of MK-801, guinea pigs s howed only occasional vacuolated neurons in the retrosplenial cortex, However, affected neurons (mainly large pyramidal cells of layer V) we re found in the frontoparietal neocortex. The reaction was limited aft er 1 mg/kg, and seemed to reach a maximum at 4 mg/kg, Rats injected wi th 1 mg/kg MK-801 showed an intense vacuole reaction in neurons from l ayers III-IV of the retrosplenial cortex, but no affected neurons were noted in neocortical areas, We conclude that there are significant sp ecies differences in susceptibility to, and location of, vacuolization induced by NMDA receptor antagonists. (C) 1997 Wiley-Liss, Inc.