Differential cognitive, behavioral, and neurochemical responses to acute chlorpyrifos exposure in normotensive compared to hypertensive adult rats

IF 2.8 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology Pub Date : 2025-11-01 Epub Date: 2025-10-19 DOI:10.1016/j.ntt.2025.107565

Gabriel Gavazza Noé , Larissa de Jesus Corrêa , Janne Ketly da Silva Oliveira , Karoline de Oliveira Sant'Anna , Vitor Sampaio Minassa , Andrew Vieira Aitken , Karla Nivea Sampaio , Vanessa Beijamini

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引用次数: 0

Abstract

Clinical and preclinical evidence points to a bilateral association between cardiovascular diseases (CVD) and mental disorders such as anxiety and depression. We previously reported that exposure to organophosphate (OP) compounds, such as chlorpyrifos (CPF), promotes cardiovascular damage and behavioral alterations in normotensive rats. Also, spontaneously hypertensive rats (SHR), a well-established rodent model of hypertension, exhibit more severe symptoms of acute CPF toxicosis and higher mortality rates, likely due to lower plasma butyrylcholinesterase (BuChE) activity. The potential role of pre-existing hypertension in increasing susceptibility to acute OP toxicity, particularly in relation to psychiatric disorders, remains an open question. Given this, we investigated whether SHR are more susceptible than normotensive Wistar rats to the damage caused by acute CPF exposure on innate (elevated plus maze, EPM; light-dark transition, LDT; and open field tests) and learned (contextual fear conditioning) anxiety-like behaviors. A single dose of CPF (20 mg/kg) induced an anxiolytic-like behavior in SHR exposed to the EPM and no effect in Wistar rats. CPF acute intoxication increased fear expression in both strains, but impaired memory extinction only in Wistar rats. CPF inhibited BuChE in Wistar at all tested doses (10, 20 and 30 mg/kg), whereas inhibition occurred only at the highest dose in SHR. CPF also decreased acetylcholinesterase (AChE) activity in the hippocampus and prefrontal cortex of both strains. In summary, acute intoxication with CPF induces strain-dependent behavioral changes. SHRs intoxicated with CPF may not be the most suitable model for studying anxiety susceptibility to OP intoxication in previously hypertensive rats.

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与高血压大鼠相比，正常大鼠对毒死蜱急性暴露的认知、行为和神经化学反应的差异

临床和临床前证据表明，心血管疾病（CVD）与焦虑和抑郁等精神障碍之间存在双边关联。我们之前报道过暴露于有机磷（OP）化合物，如毒死蜱（CPF），会促进正常血压大鼠的心血管损伤和行为改变。此外，自发性高血压大鼠（SHR），一种公认的高血压啮齿动物模型，表现出更严重的急性CPF中毒症状和更高的死亡率，可能是由于血浆丁基胆碱酯酶（BuChE）活性较低。预先存在的高血压在增加急性OP毒性易感性中的潜在作用，特别是与精神疾病有关，仍然是一个悬而未决的问题。鉴于此，我们调查了SHR是否比正常的Wistar大鼠更容易受到急性CPF暴露对先天（升高加上迷宫、EPM、明暗转换、LDT和开放场地测试）和习得（情境恐惧条件反射）焦虑样行为造成的损害。单剂量CPF（20 mg/kg）在暴露于EPM的SHR中诱导焦虑样行为，而对Wistar大鼠无影响。CPF急性中毒增加了两种毒株的恐惧表达，但只损害了Wistar大鼠的记忆消失。CPF在所有测试剂量（10、20和30 mg/kg）下均抑制Wistar中的BuChE，而在SHR中仅在最高剂量时发生抑制。CPF还降低了海马和前额叶皮层乙酰胆碱酯酶（AChE）的活性。综上所述，CPF急性中毒可诱导菌株依赖性行为改变。CPF中毒的SHRs可能不是研究既往高血压大鼠OP中毒焦虑易感性的最合适模型。(243字)。

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来源期刊

Neurotoxicology and teratology 医学-毒理学

CiteScore

5.60

自引率

10.30%

发文量

审稿时长

58 days

期刊介绍： Neurotoxicology and Teratology provides a forum for publishing new information regarding the effects of chemical and physical agents on the developing, adult or aging nervous system. In this context, the fields of neurotoxicology and teratology include studies of agent-induced alterations of nervous system function, with a focus on behavioral outcomes and their underlying physiological and neurochemical mechanisms. The Journal publishes original, peer-reviewed Research Reports of experimental, clinical, and epidemiological studies that address the neurotoxicity and/or functional teratology of pesticides, solvents, heavy metals, nanomaterials, organometals, industrial compounds, mixtures, drugs of abuse, pharmaceuticals, animal and plant toxins, atmospheric reaction products, and physical agents such as radiation and noise. These reports include traditional mammalian neurotoxicology experiments, human studies, studies using non-mammalian animal models, and mechanistic studies in vivo or in vitro. Special Issues, Reviews, Commentaries, Meeting Reports, and Symposium Papers provide timely updates on areas that have reached a critical point of synthesis, on aspects of a scientific field undergoing rapid change, or on areas that present special methodological or interpretive problems. Theoretical Articles address concepts and potential mechanisms underlying actions of agents of interest in the nervous system. The Journal also publishes Brief Communications that concisely describe a new method, technique, apparatus, or experimental result.