COMPETITIVE AND NONCOMPETITIVE NMDA ANTAGONISTS INDUCE SIMILAR LIMBICDEGENERATION

NEURAL degeneration was observed in a similar set of limbic structures following the continuous administration of several NMDA antagonists ( phencyclidine, dizocilpine, and LY235959). The earliest signs involved terminals and processes, followed by cell bodies. In retrosplenial co rtex the predominant staining showed a distribution very similar to th at observed for cholinergic innervations. Considerable degeneration wa s also observed in entorhinal cortex and its principal output, dentate gyrus of hippocampus, and in olfactory regions such as olfactory tube rcle and tenia tecta, and in piriform cortex. These results, when cons idered together with those from studies of glucose metabolism followin g NMDA antagonists, suggest that a hypermetabolic circuit was involved , and indicate that both competitive and non-competitive NMDA antagoni sts can induce these effects.