Dr. B. Engelsen was on leave during the performance of these studies from the Department of Neurology, University Hospital of Bergen, N-5016 Haukeland Sykehus, Norway.
2-Amino-7-Phosphonoheptanoic Acid Inhibits Insulin-Induced Convulsions and Striatal Aspartate Accumulation in Rats with Frontal Cortical Ablation
Article first published online: 5 OCT 2006
Journal of Neurochemistry
Volume 49, Issue 1, pages 121–127, July 1987
How to Cite
Chapman, A. G., Engelsen, B. and Meldrum, B. S. (1987), 2-Amino-7-Phosphonoheptanoic Acid Inhibits Insulin-Induced Convulsions and Striatal Aspartate Accumulation in Rats with Frontal Cortical Ablation. Journal of Neurochemistry, 49: 121–127. doi: 10.1111/j.1471-4159.1987.tb03403.x
- Issue published online: 5 OCT 2006
- Article first published online: 5 OCT 2006
- Received August 7, 1986; revised December 18, 1986; accepted December 18, 1986.
- Corticostriatal lesion;
- Excitatory amino acids;
- 2-Amino-7-phosphonoheptanoic acid;
- Aspartate turnover
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%. Le-sioning 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 was 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.