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THE EFFECT OF TOPICAL APPLICATION OF DIETHYL‐α‐FLUOROGLUTARATE ON THE METABOLISM AND ELECTRICAL ACTIVITY IN VIVO OF CAT CEREBRAL CORTEX 1
Author(s) -
Cohen H. P.,
Vasconetto C.,
Ayala G.F.
Publication year - 1972
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1972.tb01362.x
Subject(s) - creatine , glutamate receptor , amino acid , chemistry , excitatory postsynaptic potential , cerebral cortex , in vivo , inhibitory postsynaptic potential , metabolism , citric acid cycle , biochemistry , stimulation , alanine , endocrinology , biology , medicine , receptor , microbiology and biotechnology
— The effect of topical application of diethyl‐α‐fluoroglutarate on the primary response of cat cerebral cortex to thalamic stimulation was investigated, and samples of the involved tissue and of homologous contralateral control tissue were removed at appropriate times for biochemical analyses. Changes in electrocortical response were first noted 30–40 min after topical application of 10 μ1 (52.7 μmol) of the drug to the pericruciate gyrus . A rapid reduction in amplitude of the surface negative component of the primary response was observed initially, followed by amplitude reduction and rapid disappearance of the primary response throughout the cortical field within a few minutes after the change first observed at the surface. The effects were interpreted either as a direct action of the drug on the somadendritic membrane or an inhibition of the excitatory synaptic impingement. Analyses of the tissues removed at the time of maximum electrocortical response indicated profound metabolic changes, including depletion of energy reserves and several Krebs cycle intermediates. Large increases in tissue levels of glucose, glucose 6‐phosphate, and pyruvate were found. Changes in amino acids comprised depletion of glutamate with increased tissue levels of aspartate, GABA, NH 3 , threonine, serine and alanine. Tissues were also removed at 10 min after topical application of the drug but before the advent of electrocortical changes. Decreased levels of glutamate were associated with a rise in tissue aspartate. Tissue levels of the other amino acids were unchanged. Glucose, glucose 6‐phosphate and pyruvate levels were increased, lactate and ATP levels were unchanged, and P‐creatine, α‐KG and malate levels were reduced. We believe that the observed pattern of changes represents responses of the cerebral cortex to either a block in the synthesis of glutamate or in oxidation of pyruvate, with consequent interference with oxidative and energy metabolism and eventual depression of cortical electrical activity.