Long Term Effects of the Administration of Quisqualic Acid into the Substantia Nigra of Rats
Dr. Leah Chase, Hope College
Dr. Christopher Barney, Hope College
Dr. John Shaughnessy, Hope College
Previous in vitro studies in rat hippocampal slices have demonstrated that the non-NMDA receptor and mGluR agonist, quisqualic acid (QUIS) causes sensitization of pyramidal cell neurons which persists for hours following the removal of QUIS from the extracellular medium. This effect is not blocked by antagonists of either non-NMDA receptors but is blocked by non-transportable inhibitors of the cystine/glutamate exchanger, System xc-. Based on these studies, we hypothesized that QUIS may trigger a slowly developing neurodegeneration. In this study, QUIS and/or S-4-carboxyphenylglycine (CPG), a non-transportable inhibitor of system xc- was injected into the substantia nigra of rats. The rats’ motor performance, anxiety, and spatial learning were tested for 25 weeks post-injection. QUIS injections into the substantia nigra led to changes in performance in the Morris Water Maze five months following injection. QUIS-treated rats traveled a greater distance and took longer to find a hidden platform than did rats not treated with QUIS. However, there were no other motor effects observed as a result of QUIS treatment. QUIS had no effect on performance on the Rotarod task or the hanging wire task. There also was no reliable effect of QUIS on gate or risk taking behavior. These results indicate that central administration of QUIS into the substantia nigra has minimal effects on the behavior of rats. Previous studies in which QUIS was injected into the hippocampus led to changes in spatial learning ability, as predicted, five months following QUIS injection. However, the results from the substantia nigra-injected rats suggest there may be fewer neurons in this region of the brain, unlike the hippocampus, which are susceptible to QUIS excitotoxicity.
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