Effect of ethanol on audiogenic seizures in C57BL/6J and DBA/2J mice

DBA/2J mice, 30 or 60 days of age, representing low and no susceptibility to audiogenic seizures (AGS), were injected with 5 g/kg ethanol (ETOH) i.p. and tested for AGS from 5 to 10 1/2 h later. No responsiveness was seen to 6 h in either group. A rapid linear rise in AGS scores to a peak at 9 1/2 to 10 1/2 h was seen in the 30 day-old mice. In the 60 day-old mice, a period of reinduction of susceptibility was found, peaking at 10 h, in mice nominally presumed near-deaf at this age. In a second experiment, C57BL/6J mice were audiogenic-primed at 16 days of age and injected at 21 days. These ages were chosen to represent an intermediate level of AGS in controls. Mice received 4 g/kg of ETOH and were found to be completely protected from AGS through 4 1/2 h, followed by a transient overshoot at 9 h. Data with 4 g/kg show the same time course of suppression of seizures, followed by a brief period of potentiation as has been observed for other seizure-inducing methods. A more complete time course study was then performed using 2 g/kg, the approximate maximal dose tolerated with minimal overt behavioral changes in these mice. At this dose, mice were maximally protected for 2 to 3 h, and the overshoot in AGS scores was found at 5 to 5 1/2 h. The reported studies demonstrate a controlled experimental approach to investigate the biochemical events associated with nervous system function during seizure activity.