Competitive and non-competitive NMDA antagonists induce similar limbic degeneration

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 cortex the predominant staining showed a distribution very similar to that observed for cholinergic innervations. Considerable degeneration was also observed in entorhinal cortex and its principal output, dentate gyrus of hippocampus, and in olfactory regions such as olfactory tubercle and tenia tecta, and in piriform cortex. These results, when considered together with those from studies of glucose metabolism following NMDA antagonists, suggest that a hypermetabolic circuit was involved, and indicate that both competitive and non-competitive NMDA antagonists can induce these effects.