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MK‐801 neurotoxicity in the guinea pig cerebral cortex: Susceptibility and regional differences compared with the rat
Author(s) -
Raboisson Patrick,
Flood Karin,
Lehmann Anders,
Berge OddGeir
Publication year - 1997
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19970801)49:3<364::aid-jnr11>3.0.co;2-#
Subject(s) - vacuolization , nmda receptor , neocortex , neurotoxicity , guinea pig , saline , retrosplenial cortex , cortex (anatomy) , excitotoxicity , endocrinology , medicine , antagonist , chemistry , cerebral cortex , neuroscience , biology , toxicity , receptor
N‐methyl‐D‐aspartate (NMDA) receptor antagonists induce transient vacuole formation in neurons of the retrosplenial cortex and, after higher doses, necrosis in the same region. To our knowledge, all studies demonstrating these effects have been carried out in rats or mice. The present study investigated whether vacuolization occurs in the guinea pig, 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 showed only occasional vacuolated neurons in the retrosplenial cortex. However, affected neurons (mainly large pyramidal cells of layer V) were found in the frontoparietal neocortex. The reaction was limited after 1 mg/kg, and seemed to reach a maximum at 4 mg/kg. Rats injected with 1 mg/kg MK‐801 showed an intense vacuole reaction in neurons from layers III–IV of the retrosplenial cortex, but no affected neurons were noted in neocortical areas. We conclude that there are significant species differences in susceptibility to, and location of, vacuolization induced by NMDA receptor antagonists. J. Neurosci. Res. 49:364–371, 1997. © 1997 Wiley‐Liss, Inc.