2‐Amino‐7‐Phosphonoheptanoic Acid Inhibits Insulin‐Induced Convulsions and Striatal Aspartate Accumulation in Rats with Frontal Cortical Ablation
- 1 July 1987
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 49 (1), 121-127
- https://doi.org/10.1111/j.1471-4159.1987.tb03403.x
Abstract
Pretreatment of rats with the excitatory amino acid antagonist 2-amino-7-phosphonoheptanoic acid (2-APH; 0.5 mmol/kg, i.p.) protected against insulin-induced clonic seizures. Complete protection was observed in 38% of the rats and partial protection in an additional 50%. Lesioning of the corticostriatal pathway by frontal cortical ablation caused decreases in the striatal levels of aspartate (-28%) and glutamate (-18%), an increase in striatal glutamine level (45%), and decreased high-affinity uptake of D-[3H]aspartate (-27%) in the lesioned dorsal neostriatum. Insulin-induced hypoglycemia caused a predicted sharp increase in aspartate level (165%) and decreased glutamate (-20%) and glutamine (-38%) levels in the intact striatum. Pretreatment of rats with 2-APH significantly reversed the insulin-induced changes in striatal aspartate, glutamate, and glutamine levels, especially in the intact hemisphere. In normoglycemic control rats, the "metabolic," i.e., concentration in the lesioned hemisphere, aspartate pool constituted 72% and the "synaptic," i.e., the concentration difference between the intact and lesioned hemispheres, 28% of the total striatal aspartate pool. 2-APH had no effect on the level of "metabolic" aspartate in the striata of normoglycemic rats but caused an almost complete suppression of "synaptic" aspartate. Following insulin-induced hypoglycemia, the "metabolic" aspartate pool doubled, whereas the "synaptic" aspartate pool increased 3.5-fold in the absence of 2-APH. The insulin-induced rise in "synaptic" aspartate level was almost completely blocked by 2-APH (a 5% rise instead of a 3.5-fold rise). The turnover of "metabolic" aspartate also affected by 2-APH, but to a lesser extent (a 25% rise in the presence vs. a 94% rise in the absence of 2-APH). The striatal changes in levels of dicarboxylic acids after systemic 2-APH administration can be most simply explained in terms of an action of 2-APH in the cortex blocking excitatory inputs to the corticostriatal pathway.Keywords
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