The neurobehavioral consequences of N-methyl-D-aspartate (N-MDA) administration in rats

Evidence is accumulating which suggests that brain damage associated with certain neurodegenerative conditions may be at least partially produced by the overactivation of N-methyl-D-aspartate receptors (N-MDA). To systematically examine the overactivation of N-MDA receptors, N-MDA was administered directly to the frontal cortex and to the hippocampus in rats. It was found that cortical application (1, 2, or 4 mg) had no effect on motor activity 1, 2, or 3 wk after surgery. Four mg N-MDA failed to affect acquisition of a water maze task despite large decreases in cortical width at the site of application. In addition, no alterations in striatal, hippocampal, or cortical cholineacetyltransferase (CHAT) activity were detected after cortical application. Intrahippocampal N-MDA (0, 2.5, 5.0, 10.0, 20.0 micrograms/site) increased motor activity in a dose dependent manner 1, 2, and 3 wk post-surgery. Furthermore, 10 micrograms/site significantly impaired water maze acquisition. Intrahippocampal N-MDA also increased hippocampal CHAT activity and resulted in a loss of pyramidal and dentate granule cells. These results suggest that N-MDA may serve as a useful tool in studying the effects of glutaminergic hyperfunction and its role in neurodegenerative disorders which involve the overactivation of N-MDA receptors.