HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Behavioral assessment of NIH Swiss mice acutely intoxicated with tetramethylenedisulfotetramine.

Abstract
Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison that is thought to trigger seizures by inhibiting the function of the type A gamma-aminobutyric acid receptor (GABAAR). Acute intoxication with TETS can cause vomiting, convulsions, status epilepticus (SE) and even death. Clinical case reports indicate that individuals who survive poisoning may exhibit long-term neuropsychological issues and cognitive deficits. Therefore, the objective of this research was to determine whether a recently described mouse model of acute TETS intoxication exhibits persistent behavioral deficits. Young adult male NIH Swiss mice received a seizure-inducing dose of TETS (0.15mg/kg, ip) and then were rescued from lethality by administration of diazepam (5mg/kg, ip) approximately 20min post-TETS-exposure. TETS-intoxicated mice typically exhibited 2 clonic seizures prior to administration of diazepam with no subsequent seizures post-diazepam injection as assessed using behavioral criteria. Seizures lasted an average of 72s. Locomotor activity, anxiety-like and depression-relevant behaviors and cognition were assessed at 1week, 1month and 2months post-TETS exposure using open field, elevated-plus maze, light↔dark transitions, tail suspension, forced swim and novel object recognition tasks. Interestingly, preliminary validation tests indicated that NIH Swiss mice do not respond to the shock in fear conditioning tasks. Subsequent evaluation of hot plate and tail flick nociception tasks revealed that this strain exhibits significantly decreased pain sensitivity relative to age- and sex-matched C57BL/6J mice, which displayed normal contextual fear conditioning. NIH Swiss mice acutely intoxicated with TETS exhibited no significant anxiety-related, depression-relevant, learning or memory deficits relative to vehicle controls at any of the time points assessed with the exception of significantly increased locomotor activity at 2months post-TETS intoxication. The general absence of long-term behavioral deficits in TETS-intoxicated mice on these six assays suggests that the neurobehavioral consequences of TETS exposure described in human survivors of acute TETS intoxication are likely due to sustained seizure activity, rather than a direct effect of the chemical itself. Future research efforts are directed toward developing an animal model that better recapitulates the SE and seizure duration reported in humans acutely intoxicated with TETS.
AuthorsBrenna M Flannery, Jill L Silverman, Donald A Bruun, Kyle R Puhger, Mark R McCoy, Bruce D Hammock, Jacqueline N Crawley, Pamela J Lein
JournalNeurotoxicology and teratology (Neurotoxicol Teratol) 2015 Jan-Feb Vol. 47 Pg. 36-45 ISSN: 1872-9738 [Electronic] United States
PMID25446016 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Bridged-Ring Compounds
  • Convulsants
  • GABA Modulators
  • tetramethylenedisulfotetramine
  • Diazepam
Topics
  • Adaptation, Ocular (drug effects)
  • Animals
  • Anxiety (chemically induced, drug therapy)
  • Behavior, Animal (drug effects)
  • Bridged-Ring Compounds (toxicity)
  • Cognition Disorders (chemically induced)
  • Convulsants (toxicity)
  • Diazepam (therapeutic use)
  • Dose-Response Relationship, Drug
  • Exploratory Behavior (drug effects)
  • GABA Modulators (therapeutic use)
  • Male
  • Maze Learning (drug effects)
  • Mice
  • Mice, Inbred Strains
  • Neurotoxicity Syndromes (drug therapy, etiology, physiopathology)
  • Recognition, Psychology (drug effects)
  • Seizures (chemically induced)
  • Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: