Efeito da exposição aguda ao clorpirifós nas respostas autonômicas e comportamentais em ratos no medo condicionado ao contexto: a influência de diferentes condições experimentais no desfecho
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Data
2025-08-28
Autores
Noé, Gabriel Gavazza
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Universidade Federal do Espírito Santo
Resumo
Organophosphates (OPs) are a class of compounds widely used worldwide. Evidence suggests that different exposure patterns to OP compounds induce cardiovascular, respiratory, behavioral, cognitive, motor, oxidative/nitrosative, and inflammatory impairments. In previous studies, we observed that a single-dose intoxication with chlorpyrifos (CPF), an OP, caused behavioral impairments in contextual fear conditioning (CFC). However, we did not evaluate whether acute intoxication would impair the autonomic response in CFC. Furthermore, studies show that the use of anesthetics, such as ketamine and xylazine, can interfere with behavioral and cardiovascular responses. Therefore, we investigated the behavioral, autonomic, and biochemical effects of acute exposure to CPF in rats subjected to CFC, exploring how variations in experimental conditions, such as protocol order, anesthesia, surgery, and time, can influence the results obtained. To this end, adult Wistar rats were subjected to the CFC test. The CFC was divided into three sessions: conditioning, extinction, and recall extinction. Exposure to CPF (20 mg/kg, i.p.) always occurred after conditioning. Autonomic (mean arterial pressure, MAP, and heart rate, HR) and behavioral (freezing) parameters were recorded during the extinction and recall extinction sessions. Four different protocols were performed: Protocol 1 – femoral artery cannulation surgery under ketamine/xylazine (80/10 mg/kg) anesthesia 24 h before conditioning and the effect of CPF on the CFC 24 h after intoxication; Protocol 2 – cannulation surgery 24 h after conditioning and the effect of CPF on the CFC 48 h after intoxication; Protocol 3 – extinction session 48 h after conditioning and CPF administration, in the absence of surgery and anesthesia; Protocol 4 – anesthesia with the ketamine/xylazine mixture, 24 h after conditioning, in the absence of surgery. At the end of the experiments, the animals were euthanized for sample collection to assess acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzyme activity, and to quantify nitrosative stress markers (NO2-, NO3-, and total NO) in the hippocampus and trunk. In protocol 1, acute CPF intoxication impaired extinction and increased fear expression 24 h after intoxication without affecting MAP or HR. Conversely, in protocol 2, acute CPF exposure altered the pressor and tachycardic responses of intoxicated animals that underwent surgery 24 h after conditioning, without affecting behavioral responses. In protocols 3 and 4, acute CPF poisoning impaired fear extinction, while the anesthetic combination of ketamine and xylazine and the anesthetic combination with CPF also impaired the extinction of conditioned fear. In all four protocols, it was observed that poisoning led to cholinesterase inhibition. Furthermore, acute CPF poisoning altered the levels of NO2-, NO3-, and total NO in animals 72 h after poisoning. Thus, it is concluded that acute CPF poisoning of rats impairs behavioral and cardiovascular responses in the CFC, and that the anesthetic combination and surgery may interfere with these results.
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Palavras-chave
Organofosforado , Medo condicionado ao contexto , Estresse nitrosativo