Document Detail


Audiogenic seizure susceptibility is induced by termination of continuous infusion of gamma-aminobutyric acid or an N-methyl-D-aspartic acid Antagonist into the inferior colliculus.
MedLine Citation:
PMID:  11520129     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The inferior colliculus (IC) is strongly implicated in seizure initiation in a genetic form of audiogenic seizures (AGS) and in AGS observed during ethanol withdrawal (ETX). Ethanol is known to block the actions of excitatory amino acids (EAA) and enhance the actions of gamma-aminobutyric acid (GABA) in several brain areas, including the IC. The present study investigated the effects on susceptibility to AGS following withdrawal from continuous blockade of N-methyl-D-aspartic acid (NMDA) receptors or continuous activation of GABA receptors in the IC. This involved infusion of GABA (1 M) or a competitive NMDA antagonist, DL-2-amino-7-phosphonoheptanoic acid (AP7, 1 mM), at 0.25 microl/h for 7 days using an Alzet osmotic minipump. Following abrupt termination of the infusion, AGS susceptibility began at 30 min. The incidence of AGS was 38.9 and 56.3% following GABA and AP7 withdrawal, respectively. The AGS behaviors observed during withdrawal, which included wild running and bouncing clonus, were very similar to those evoked by acoustic stimuli during ETX. AGS susceptibility lasted for several hours and in 13% of animals persisted for up to 6 months. The current results support diminished GABAergic and elevated glutamatergic function in the IC as the critical mechanisms and sites for AGS initiation. The present study, coupled with previous evidence that chronic ethanol exposure reduced GABA-mediated inhibition and enhanced EAA-mediated excitation, suggests that these amino acid receptor-mediated alterations in the IC are key elements in initiating AGS during ethanol withdrawal.
Authors:
L Yang; C Long; C L Faingold
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental neurology     Volume:  171     ISSN:  0014-4886     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-08-24     Completed Date:  2001-10-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  147-52     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Affiliation:
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9629, USA.
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MeSH Terms
Descriptor/Qualifier:
2-Amino-5-phosphonovalerate / analogs & derivatives
Acoustic Stimulation / adverse effects
Animals
Behavior, Animal / drug effects
Catheterization
Disease Susceptibility / chemically induced*,  complications
Drug Administration Routes
Epilepsy, Reflex / chemically induced*,  complications,  physiopathology
Excitatory Amino Acid Antagonists*
Inferior Colliculi / drug effects*,  physiopathology
Infusion Pumps, Implantable
Male
Rats
Rats, Sprague-Dawley
Reaction Time / drug effects
Time Factors
gamma-Aminobutyric Acid*
Grant Support
ID/Acronym/Agency:
AA11628/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 56-12-2/gamma-Aminobutyric Acid; 76726-92-6/2-Amino-5-phosphonovalerate; 85797-13-3/2-amino-7-phosphonoheptanoic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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