Decreased GABA and increased glutamate receptor-mediated activity on inferior colliculus neurons in vitro are associated with susceptibility to ethanol withdrawal seizures

Cessation of ethanol administration in ethanol-dependent rats results in an ethanol withdrawal (ETX) syndrome, including audiogenic seizures (AGS). The inferior colliculus (IC) is the initiation site fur AGS, and membrane properties of IC neurons exhibit hyperexcitability during ETX. Previous studies observed that ETX alters GABA and glutamate neurotransmission in certain brain sites. The present study evaluated synaptic properties and actions of GABA or glutamate antagonists during ETX in IC dorsal cortex (ICd) neurons in brain slices from rats treated with ethanol intragastrically 3 times daily for 4 days. A significant increase of spontaneous action potentials (APs) was observed during ETX. The width, area and rise time of excitatory postsynaptic potentials (EPSPs) evoked by stimulation in the commissure of IC were significantly elevated during ETX. A fast EPSP was sensitive to block by the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and a slow EPSP was sensitive to the NMDA receptor antagonist, 2-amino-5-phosphonovalerate (AP5). However, during ETX the concentration of CNQX or AP5 needed to block these EPSPs was elevated significantly. Inhibitory postsynaptic potentials (IPSPs) in ICd neurons evoked in both normal and ETX rats were blocked by the GABA(A) antagonist, bicuculline. However, IPSPs during ETX displayed a significantly greater sensitivity to bicuculline. These data indicate that decreased GABA(A)-mediated inhibition and increased glutamate-mediated excitability in IC may both be critical mechanisms of ACS initiation during ETX, which is similar to observations in a genetic form of AGS. The common changes in IC neurotransmission in these AGS forms may be general mechanisms subserving AGS and other forms of auditory system pathophysiology in which the IC is implicated. (C) 2000 Elsevier Science B.V. All rights reserved.