The efficacy of γ-aminobutyric acid type A receptor (GABA _AR) subtype-selective positive allosteric modulators in blocking tetramethylenedisulfotetramine (TETS)-induced seizure-like behavior in larval zebrafish with minimal sedation.

ABSTRACT: The chemical threat agent tetramethylenedisulfotetramine (TETS) is a γ-aminobutyric acid type A receptor (GABA _AR) antagonist that causes life threatening seizures. Currently, there is no specific antidote for TETS intoxication. TETS-induced seizures are typically treated with benzodiazepines, which function as nonselective positive allosteric modulators (PAMs) of synaptic GABA_ARs. The major target of TETS was recently identified as the GABA_AR α2β3γ2 subtype in electrophysiological studies using recombinantly expressed receptor combinations. Here, we tested whether these in vitro findings translate in vivo by comparing the efficacy of GABA_AR subunit-selective PAMs in reducing TETS-induced seizure behavior in larval zebrafish. We tested PAMs targe

SUBMITTER: Mundy PC 

PROVIDER: S-EPMC8514104 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature