Amino acid changes in the mouse brain during audiogenic seizures and recovery

Abstract

Presensitized mice of the A2G strain were subjected to the sound provided by the sustained ringing of a 100 db electric doorbell. The animal responded with a phase of running behavior beginning 10 sec after the onset of the auditory stimulus and lasting about 40–50 sec; this phase was followed by generalized tonic-clonic convulsions, catatonic state and recovery. The brain concentration of glutamate and glutamine decreased significantly during the running behavior phase and dropped further at the moment of maximal convulsions, whereas that of aspartate and GABA remained unchanged during running behavior and decreased during seizures. During the phase of recovery the normal levels were rapidly restored; glutamine showed the highest rate of accumulation, in contrast to GABA, showing the slower one. Subcutaneous administration of GABA led to a significant increase in the brain concentration of GABA and glutamate, which was roughly proportional to the administered dose. Maximal increases were observed 30 min after administration and returned to normal in 150 min. Systemically administered GABA afforded a protection against sound-induced seizures, decreasing the percentage of the number of animals convulsing. In spite of this protection, the concentration of amino acids in brain from pretreated mice, regardless if they convulsed or not, was essentially the same as that found in the brain of nonexposed control mice; however, a marked decrease was observed in GABA and, to a much lesser degree, in glutamate when compared with pretreated non-exposed controls. The results led to the conclusion that the brain concentration of GABA was not a determining factor in the production of sound-induced seizures.