Increased responsiveness of pontine reticular formation neurons associated with audiogenic seizure susceptibility during ethanol withdrawal.
Susceptibility to audiogenic seizures (AGS) is observed during ethanol withdrawal (ETX). The pontine reticular formation (PRF) is implicated in the propagation pathway for AGS during ETX. The present study examined the changes in single PRF neuronal firing patterns produced by ethanol and during ETX following repeated intragastrically administered ethanol. Microwire electrode bundles were implanted into PRF and single neuronal responses in freely moving rats were examined. During initial ethanol administration the animals were stuporous, and spontaneous and acoustically-evoked PRF neuronal firing were reduced significantly. During ETX the animals were susceptible to AGS and displayed agitated and irritable behavior. At this time a significant increase in spontaneous and acoustically-evoked PRF neuronal firing was observed. Repetition-induced response attenuation (habituation) of PRF neuronal responses was significantly diminished during ETX, leading to an exaggerated acoustic startle response, which may be a physiological basis for AGS. Previous reports indicate that ethanol enhances the effects of GABA and decreases the effects of glutamate. The PRF neuronal firing increases during EXT in the present study may involve the down-regulation of GABAA receptors and supesensitivity of glutamate receptors reported to occur during ETX, which could contribute to AGS susceptibility. The PRF neuronal firing increases observed in the present study in concord with previous observation of AGS blockade by PRF microinjections during ETX further support an important role of this brain region in the propagation of AGS during ethanol withdrawal.
Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield 62794.
C L
CL
Faingold
A
A
Riaz
D000161:Acoustic Stimulation; D000435:Alcoholic Intoxication / Q000503:physiopathology; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D006185:Habituation, Psychophysiologic; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011149:Pons / Q000502:physiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D012154:Reticular Formation / Q000502:physiology / Q000503:physiopathology*; D012640:Seizures / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D011963:Receptors, GABA-A; D000431:Ethanol; D005680:gamma-Aminobutyric Acid