Changes in Excitatory Amino Acid Receptor Binding in the Intact and Decorticated Rat Neostriatum Following Insulin‐Induced Hypoglycemia

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Abstract
An involvement of excitatory amino acid (EAA) transmitter–receptor interactions in the development of hypoglycemia‐induced neuronal damage has been suggested. We report here on the binding to EAA receptors in the rat caudate nucleus and cerebral cortex, during and following severe insulin‐induced hypoglycemia with an isoelectric EEG of 10 or 30 min duration. The binding of α[3H]amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid ([3H]AMPA) to quisqualate receptors, [3H]kainic acid (KA) to kainate receptors, and [3H]glutamate to N‐methyl‐D‐aspartate (NMDA)‐sensitive sites was determined by quantitative autoradiography. During EEG isoelectricity, AMPA binding was reduced by approximately 40%, which could represent quisqualate receptor desensitization. One hour following glucose‐induced recovery, AMPA binding was no longer different from control level. As the recovery period was prolonged to 1 or 4 weeks, AMPA binding decreased. The decrease was more pronounced in the dorsolateral than in the ventromedial part of the striatum. This correlates with the distribution of neuronal damage, and probably reflects loss of receptor binding sites due to cell death. During the period of EEG silence there was a tendency toward an increase in NMDA displaceable glutamate binding. Following 4 weeks of recovery, binding to NMDA receptors was significantly decreased. Glutamate binding to NMDA‐sensitive sites was remarkably resistant to neuronal necrosis and was not significantly different from control values in the dorsolateral caudate 1 week following the hypoglycemic coma. No changes in KA binding were found until 1 week posthypoglycemia, when a significant reduction in binding was noted in the lateral striatum. Two weeks following partial unilateral cortical ablation, binding to NMDA receptors in the striatum decreased in the lesioned hemisphere in control animals and remained significantly lower than in the contralateral hemisphere during EEG isoelectricity. In contrast, no hemispheric differences in AMPA binding were observed. The lack of desensitization of NMDA receptors during EEG isoelectricity and their relative resistance to neuronal necrosis could be of significance for the development of hypoglycemic neuronal damage.