Noe_2025_Neurotoxicol.Teratol__107565

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. (243 words).