2-Amino-7-Phosphonoheptanoic Acid Inhibits Insulin-Induced Convulsions and Striatal Aspartate Accumulation in Rats with Frontal Cortical Ablation |
| |
Authors: | A. G. Chapman B. Engelsen B. S. Meldrum |
| |
Affiliation: | Department of Neurology, Institute of Psychiatry, De Crespigny Park, London, England |
| |
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).(ABSTRACT TRUNCATED AT 250 WORDS) |
| |
Keywords: | Corticostriatal lesion Excitatory amino acids 2-Amino-7-phosphonoheptanoic acid Convulsions Hypoglycemia Aspartate turnover |
|
|