SL 82.0715, an NMDA antagonist acting at the polyamine site, does not induce neurotoxic effects on rat cortical neurons.
In the present study, we have examined by light and electron microscopy whether SL 82.0715, a polyamine site-directed N-methyl-D-aspartate (NMDA) antagonist, causes pathological changes in cerebrocortical neurons similar to those observed with NMDA receptor channel blockers in the rat brain. Dizocilpine (1, 2 and 5 mg.kg-1, s.c.) induced a dose-dependent vacuolization of the neuronal cytoplasm in specific neurons of the retrosplenial and posterior cingulate cortices (layers III and IV) even at the lowest dose studied, at 6 h post-injection. In contrast, SL 82.0715 (10 and 30 mg.kg-1 i.p., 6 h post-injection) did not induce such morphological alterations. These results indicate that NMDA receptor blockade is not necessarily associated with alterations of cortical neuronal morphology.
Duval
D
D
Synthelabo Recherche (L.E.R.S.), Biology Department, Bagneux, France.
Roome
N
N
Gauffeny
C
C
Nowicki
J P
JP
Scatton
B
B
D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D016291:Dizocilpine Maleate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D010880:Piperidines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014617:Vacuoles / Q000187:drug effects
D015317:Biogenic Polyamines; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C058083:eliprodil