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

Autor: Rodrigues JVF; Pharmaceutical Sciences Graduate Program, Health Sciences Centre, Federal University of Espírito Santo, Vitória, ES, Brazil., Vidigal APP; Pharmaceutical Sciences Graduate Program, Health Sciences Centre, Federal University of Espírito Santo, Vitória, ES, Brazil., Minassa VS; Pharmaceutical Sciences Graduate Program, Health Sciences Centre, Federal University of Espírito Santo, Vitória, ES, Brazil., Batista TJ; Pharmaceutical Sciences Graduate Program, Health Sciences Centre, Federal University of Espírito Santo, Vitória, ES, Brazil; Physiological Sciences Graduate Program, Health Sciences Centre, Federal University of Espírito Santo, Vitória, ES, Brazil., de Lima RMS; Neuroscience Graduate Program, Health Sciences, Centre, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil., Funck VR; Pitágoras College, Guarapari, ES, Brazil., Antero LS; Medical School, State University of Mato Grosso do Sul, Campo Grande, MS, Brazil., Resstel LBM; Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil., Coitinho JB; Pharmaceutical Sciences Graduate Program, Health Sciences Centre, Federal University of Espírito Santo, Vitória, ES, Brazil; Department of Physiological Sciences, Health Science Centre, Federal University of Espírito Santo, Vitória, ES, Brazil., Bertoglio LJ; Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC, Brazil., Sampaio KN; Pharmaceutical Sciences Graduate Program, Health Sciences Centre, Federal University of Espírito Santo, Vitória, ES, Brazil., Beijamini V; Pharmaceutical Sciences Graduate Program, Health Sciences Centre, Federal University of Espírito Santo, Vitória, ES, Brazil. Electronic address: vanessa.harres@ufes.br.
Jazyk: angličtina
Zdroj: Neurotoxicology and teratology [Neurotoxicol Teratol] 2020 Nov - Dec; Vol. 82, pp. 106929. Date of Electronic Publication: 2020 Oct 06.
DOI: 10.1016/j.ntt.2020.106929
Abstrakt: 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.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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