A single dose of the organophosphate triazophos induces fear extinction deficits accompanied by hippocampal acetylcholinesterase inhibition.

Abstract

Acute organophosphate (OP) poisoning, particularly by suicide attempts, generates high mortality and morbidity. Few studies have systematically addressed the consequences of acute OP intoxication on cognition and memory of survivors. Preclinical evidence suggests that acute OP-induced effects are associated with inhibiting the brain acetylcholinesterase (AChE) enzyme. The OP triazophos has been used worldwide, although its effects on mnemonic processing are yet to be investigated. Based on the above, the present study investigated whether acute triazophos intoxication interferes with the expression and extinction of contextual fear memory in rats. Hippocampal and amygdalar AChE activity and plasma butyrylcholinesterase (BChE) were measured at the end of the experiment to confirm the cholinergic overstimulation. Independent cohorts of animals intoxicated with triazophos were evaluated in the novel object recognition (NOR) test, a less aversive associative memory task. At the dose of 15 mg/kg, triazophos administered immediately after contextual fear conditioning impaired the extinction but not the expression of freezing behavior. Triazophos poisoning induced no changes in the discrimination index in the NOR test. Triazophos inhibited the AChE activity in a time- and brain region-dependent manner. Our findings suggest that fear memory extinction deficits induced by acute triazophos intoxication are accompanied by hippocampal AChE inhibition. The deficient fear extinction associated with acute OP poisoning may represent a behavioral and biochemical phenotype helpful to study mechanisms of neurotoxicity and treatment approach of OP suicide survivors.

• Authors: João Vitor Ferreira Rodrigues, Anna Paula Perin Vidigal, Vítor Sampaio Minassa, Thatiany Jardim Batista, Randriely Merscher Sobreira de Lima, Vinícius Rafael Funck, Leandro S Antero, Leonardo Barbosa Moraes Resstel, Juliana Barbosa Coitinho, Leandro Jose Bertoglio, Karla Nívea Sampaio, Vanessa Beijamini
• Journal: Neurotoxicology and teratology (Neurotoxicol Teratol) 2020 Nov - Dec Vol. 82 Pg. 106929 ISSN: 1872-9738 [Electronic] United States
• PMID: 33031921 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Cholinesterase Inhibitors
• Organophosphates
• Organothiophosphates
• Triazoles
• triazophos
• Acetylcholinesterase

Topics

• Acetylcholinesterase (drug effects, metabolism)
• Animals
• Cholinesterase Inhibitors (toxicity)
• Conditioning, Classical (drug effects)
• Extinction, Psychological (drug effects)
• Fear (drug effects)
• Hippocampus (drug effects, enzymology)
• Male
• Organophosphates (toxicity)
• Organothiophosphates (toxicity)
• Rats
• Rats, Wistar
• Triazoles (toxicity)