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.