ETHANOL WITHDRAWAL INDUCES INCREASED FIRING IN INFERIOR COLLICULUS NEURONS ASSOCIATED WITH AUDIOGENIC-SEIZURE SUSCEPTIBILITY

Ethanol withdrawal (ETX) in ethanol-dependent rats results in suscepti bility to seizures, including generalized tonic-clonic audiogenic seiz ures (AGS). The inferior colliculus (IC) is strongly implicated in AGS initiation during ETX, but IC neuronal mechanisms subserving AGS are unclear. The present study examined IC (central nucleus) single neuron al firing during repeated (4 day) intragastric ethanol administration and during ETX. This involved microwire electrodes implanted chronical ly into freely moving rats and acoustic stimulation in intensities up to 105 dB SPL. During initial ethanol administration the animals were stuporous, and IC spontaneous neuronal firing and acoustically evoked firing at high stimulus intensities were significantly reduced. This f iring reduction is consistent with the action of ethanol to enhance ga mma-aminobutyric acid (GABA)-mediated inhibition, which is prominent i n IC neurons at high stimulus intensities. During ETX the animals were agitated, and spontaneous IC neuronal firing and acoustically evoked firing at all stimulus intensities were significantly increased during the period of AGS susceptibility. Previous studies indicate that IC n euronal responses are tightly regulated by GABA and glutamate. The IC firing increases during ETX in the present study may involve the down- regulation of GABAA receptors and supersensitivity of glutamate recept ors reported to occur during ETX Previous studies also indicate that f ocal blockade of GABAA receptors or activation of glutamate receptors produces AGS susceptibility in normal rats. Therefore, the IC neuronal firing increases observed in the present study may play a critical ro le in initiation of AGS during ethanol withdrawal. (C) 1995 Academic P ress, Inc.