Studies on sound-induced epilepsy in mice

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Abstract
The cerebral concentrations of pyridoxal-5$^{\prime}$-phosphate and divalent transition metal ions (Cu$^{2+}$ and Zn$^{2+}$) are appreciably higher in the seizure-susceptible strain of mouse (DBA/2J) than those in normal strains (CBA/Ca and Parkes). By injecting metal ions intracranially and pyridoxal-5$^{\prime}$-phosphate intraperitoneally, we could render the normal mouse prone to sound-induced epilepsy. The behaviour of the treated mouse in response to a loud sound was essentially identical to that of the seizure-susceptible strain of mouse. The levels of glutamate and aspartate in its inferior colliculus were elevated and the concentration of $\gamma $-aminobutyrate was lowered. Glutaminase inhibitors, 6-diazo-5-oxo-L-norleucine (DON) and o-diazo-acetyl-L-serine (azaserine), and a transaminase inhibitor, 4-amino-3-isoxazolidone (L-cycloserine), when injected intraperitoneally, protected the seizure-susceptible mouse from undergoing convulsions, whereas pyridoxal-5$^{\prime}$-phosphate and methionine sulphoximine, a glutamine synthetase inhibitor, exacerbated its epileptic condition. We propose a possible sequence of biochemical events associated with susceptibility to audiogenic seizures.