BEHAVIORAL, ELECTROPHYSIOLOGICAL AND HISTOPATHOLOGICAL CHANGES FOLLOWING SUSTAINED STIMULATION OF THE PERFORANT PATHWAY INPUT TO THE HIPPOCAMPUS - EFFECT OF THE NMDA RECEPTOR ANTAGONIST, CGP-39551

Sustained stimulation of the perforant path has been shown to damage the CA1 area and impair spatial memory in rats. The pattern of cell death is similar in human epileptics, who also exhibit memory deficits. In this study we demonstrate that the learning/memory impairment in water maze test and the development of interictal spikes that also followed stimulation-induced damage were antagonized by CGP 39551. Pretreatment with this NMDA receptor antagonist also slightly diminished somatostatin cell loss in the hilus but not CA1 pyramidal cell damage. These results indicate that the impairment of spatial learning/memory seems to be dependent not only on the degree of cell degeneration in the CA1 subfield of the hippocampus but also on the frequency of interictal spikes, at least in this model of epilepsy.