Document Detail


Attenuation of epileptiform bursting by baclofen: reduced potency in elevated potassium.
MedLine Citation:
PMID:  3780917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Baclofen is an analog of the inhibitory neurotransmitter, GABA, which is used clinically to control spasticity. Recent evidence has accumulated showing this compound to have profound inhibitory effects upon hippocampal neural activity at both the cellular and circuit levels, and to attenuate epileptiform bursting in the hippocampal slice. However, it does not appear as an anticonvulsant on most traditional drug screens. Baclofen can produce inhibition by increasing potassium conductance, and therefore may fail to appear efficacious in typical anticonvulsant screens due to techniques that cause rapid and massive increases in interstitial potassium. We tested the hypothesis that baclofen is less effective at attenuating epileptiform bursting in the hippocampal slice under conditions of elevated extracellular potassium. Male Sprague-Dawley rats were decapitated and hippocampal slices were prepared. Epileptiform bursting was induced by bathing the slices in an artificial cerebrospinal fluid solution which contained either 7.0 mM K+ or 30 microM bicuculline methiodide, or by stimulus train-induced bursting. In each of these media, baclofen was applied in a random presentation of concentration format. Baclofen attenuated epileptiform bursting in both bicuculline and elevated K+, although considerably higher concentrations were necessary to attenuate bursting in high K+ than in bicuculline or after stimulus train-induced bursting. These results further support the antiepileptic actions of baclofen and provide evidence that this drug may be of value for attenuating epileptiform activity when there is not a tonic elevation of interstitial brain potassium.
Authors:
H S Swartzwelder; C P Sutch; W A Wilson
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Experimental neurology     Volume:  94     ISSN:  0014-4886     ISO Abbreviation:  Exp. Neurol.     Publication Date:  1986 Dec 
Date Detail:
Created Date:  1987-01-21     Completed Date:  1987-01-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  726-34     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects
Animals
Baclofen / pharmacology*
Bicuculline / pharmacology
Epilepsy / physiopathology*
Hippocampus / drug effects*
Male
Neural Inhibition / drug effects
Potassium / pharmacology*
Rats
Rats, Inbred Strains
Chemical
Reg. No./Substance:
1134-47-0/Baclofen; 485-49-4/Bicuculline; 7440-09-7/Potassium

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


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