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 network for audiogenic seizure (AGS) in rats undergoing ethanol withdrawal (ETX). Considerable evidence supports a role of gamma-aminobutyric acid (GABA)-mediated inhibition in normal acoustic processing in the IC. Altered GABA-mediated inhibition in the IC is suggested to be important in the control of AGS initiation. The present study used microiontophoresis to examine the effectiveness of GABA on acoustically-evoked neuronal responses in the central nucleus of the IC (ICc). GABA effectiveness was compared in normal controls and a group of animals displaying high audiogenic seizure susceptibility (100% AGS) (HAGS), and a group exhibiting a low (mean, 33%) incidence of AGS (LAGS). Ethanol was administered for 4 days in three daily doses (9-15 g/kg/day) sufficient to maintain a moderate degree of intoxication. Tonic-clonic seizures were observed in HAGS animals, while LAGS rats exhibited less severe seizures, consisting primarily of wild running. Iontophoretic application of GABA consistently inhibited ICc neuronal firing in controls and 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 significant. These data suggest that decreased GABA effectiveness in the IC neurons of HAGS susceptible animals is an important mechanism contributing to the propagation of severe AGS seen during ETX in these animals.
N'Gouemo
P
P
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62794-1222, USA.
Caspary
D M
DM
Faingold
C L
CL
D000161:Acoustic Stimulation; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000097:blood; D000431:Ethanol / Q000009:adverse effects* / Q000097:blood; D007245:Inferior Colliculi / Q000166:cytology / Q000502:physiology*; D007478:Iontophoresis; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D015431:Weight Loss / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D002492:Central Nervous System Depressants; D000431:Ethanol; D005680:gamma-Aminobutyric Acid