Ethanol withdrawal induces increased firing in inferior colliculus neurons associated with audiogenic seizure susceptibility.
Ethanol withdrawal (ETX) in ethanol-dependent rats results in susceptibility to seizures, including generalized tonic-clonic audiogenic seizures (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 neuronal firing during repeated (4 day) intragastric ethanol administration and during ETX. This involved microwire electrodes implanted chronically 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 firing reduction is consistent with the action of ethanol to enhance gamma-aminobutyric acid (GABA)-mediated inhibition, which is prominent in 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 neuronal 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 receptors reported to occur during ETX. Previous studies also indicate that focal 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 role in initiation of AGS during ethanol withdrawal.
Faingold
C L
CL
Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield 62794, USA.
Riaz
A
A
D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004198:Disease Susceptibility; D000431:Ethanol / Q000008:administration & dosage* / Q000009:adverse effects*; D007245:Inferior Colliculi / Q000166:cytology / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000431:Ethanol; D005680:gamma-Aminobutyric Acid