Brain ?-Aminobutyric acid and acoustic priming in C57BL/6Bg mice

Abstract

An initial auditory stimulus (IAS) to 19-day-old C57BL/6Bg mice is known to induce susceptibility to audiogenic seizures as tested at 28 days of age. Immediately following exposure to the IAS, whole brain levels of γ-aminobutyric acid (GABA) were transiently reduced, whereas the levels of aspartate, glutamate, norepinephrine, and 5-hydroxytryptamine remained unchanged. Pretreatment prior to the IAS with aminooxyacetic acid (AOAA) and hydrazine, two inhibitors of GABA transaminase activity that increase the levels of GABA in the brain, attenuated the acoustic priming of audiogenic seizure susceptibility. Hydroxylamine, a similar pyridoxal antagonist that does not increase GABA levels, had no effect on the acoustic priming by the IAS. Several substances acting on brain GABA system, including β-alanine, diaminobutyric acid, glutamate, and GABA itself, were also found to attenuate the acoustic priming effect of the IAS. These results indicate that GABA may be a neurochemical factor in the sequence of events following the IAS that lead to an increase in audiogenic seizure risk. Since bicuculline had no effect on acoustic priming and did not reverse the effect of AOAA, it is possible that GABA may be involved in a metabolic or regulatory role rather than in its function in postsynaptic inhibition.