DECREASED GABA EFFECTIVENESS IN THE INFERIOR COLLICULUS NEURONS DURING ETHANOL WITHDRAWAL IN RATS SUSCEPTIBLE TO AUDIOGENIC-SEIZURES

The inferior colliculus (IC) is the initiation site in the neuronal ne twork for audiogenic seizure (AGS) in rats undergoing ethanol withdraw al (ETX). Considerable evidence supports a role of gamma-aminobutyric acid (GABA)-mediated inhibition in normal acoustic processing in the I C. Altered GABA-mediated inhibition in the IC is suggested to be impor tant in the control of AGS initiation. The present study used microion tophoresis to examine the effectiveness of GABA on acoustically-evoked neuronal responses in the central nucleus of the IC (ICc). GABA effec tiveness was compared in normal controls and a group of animals displa ying high audiogenic seizure susceptibility (100% AGS) (HAGS), and a g roup exhibiting a low (mean, 33%) incidence of AGS (LAGS). Ethanol was administered for 4 days in three daily doses (9-15 g/kg/day) sufficie nt to maintain a moderate degree of intoxication. Tonic-clonic seizure s were observed in HAGS animals, while LAGS rats exhibited less severe seizures, consisting primarily of wild running. Iontophoretic applica tion of GABA consistently inhibited ICc neuronal firing in controls an d in animals undergoing ETX. However, the mean dose (current) of GABA required to produce a 50% reduction of the ICc neuronal firing in the HAGS group was nearly twice that of the control animals. The mean dose of GABA for 50% inhibition in the LAGS group was about one-half that of the control group. Both of these differences were statistically sig nificant. These data suggest that decreased GABA effectiveness in the IC neurons of HAGS susceptible animals is an important mechanism contr ibuting to the propagation of severe AGS seen during ETX in these anim als.