Document Detail

Acute and chronic acetazolamide administration in DBA and C57 mice: effects of age.
MedLine Citation:
PMID:  3081335     Owner:  NLM     Status:  MEDLINE    
The clinical utility of the carbonic anhydrase (CA) inhibitor acetazolamide (ACTZ) is limited because of rapid development of tolerance to its effects. Tolerance is thought to develop as a result of glial cell proliferation and/or increased CA synthesis. DBA mice, susceptible to audiogenic seizures (AGSs) in an age-dependent manner, have increased CA activity as compared with C57 (non-audiogenic seizure susceptible) mice at 21 and 110 days of age. The present work utilized ACTZ to help determine the relationship between increased CA activity in brain and AGSs in DBA mice. Also, minimal electroshock seizure threshold (EST) was measured at various ages in DBA and C57 mice to determine age-related changes in CNS excitability. EST was significantly lower in DBA as compared with C57 mice at 18 days and between 40 and 115 days of age, suggesting that DBA mice remain hyperexcitable to electrical stimulation after they develop resistance to AGSs. ACTZ ED50s against maximal electroshock seizures (MES) were significantly higher in DBA as compared with C57 mice at 26,36, and 115 days of age. This finding correlates with higher CA activity in this strain at 110 days of age, noted previously. However, at 21 days of age, when CA activity is also higher in DBA versus C57 mice, there were no significant differences in ACTZ ED50s against MES between the strains. ACTZ ED50s against AGSs in DBA mice were considerably lower than ACTZ ED50s against MES in either strain, suggesting that a particular fraction of CA is intimately involved in the production of AGSs.(ABSTRACT TRUNCATED AT 250 WORDS)
F L Engstrom; H S White; J W Kemp; D M Woodbury
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Epilepsia     Volume:  27     ISSN:  0013-9580     ISO Abbreviation:  Epilepsia     Publication Date:    1986 Jan-Feb
Date Detail:
Created Date:  1986-03-28     Completed Date:  1986-03-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2983306R     Medline TA:  Epilepsia     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  19-26     Citation Subset:  IM    
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MeSH Terms
Acetazolamide / administration & dosage,  therapeutic use*
Acoustic Stimulation
Brain Chemistry
Carbonic Anhydrase Inhibitors / administration & dosage,  therapeutic use*
Carbonic Anhydrases / metabolism
Drug Tolerance
Mice, Inbred C57BL / metabolism*
Mice, Inbred DBA / metabolism*
Seizures / drug therapy
Grant Support
Reg. No./Substance:
0/Carbonic Anhydrase Inhibitors; 59-66-5/Acetazolamide; EC Anhydrases

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