Behavioral consequences of organophosphorus poisoning: Insights from human exposures and rodent models

The risks of exposure to organophosphorus (OP) chemicals, predominantly used as pesticides as well as chemical warfare agents (NA, nerve agents), remain a present concern. Human studies have revealed severe neurological and psychiatric consequences of acute or chronic exposures. In order to improve the medical management of exposed patients, it is crucial to develop preclinical models that can investigate transient and persistent neurofunctional impairments. However, most research has focused on treatments that reduce mortality and seizures and restore cholinesterase activity in the short term. Few studies have evaluated the long-term benefits of these therapies. In this review, we summarize behavioral studies that assess the impact of OP exposure on affective, cognitive, and sensorimotor functions in humans and rodent models. To distinguish the specific neurobehavioral alterations induced by different OP compounds, we differentiate between lethal, single or repeated (chronic or sub-chronic) low-dose exposures to NA or pesticides. The review provides critical insights into the methodologies used to assess these alterations. Additionally, the study focuses on behavioral parameters used to evaluate treatment efficacy. Novel strategies aim to address the multifactorial consequences of OP exposure beyond seizure control, including neuroinflammation, excitotoxicity, and/or oxidative stress. Our research indicates the need for rigorous, long-term behavioral studies that incorporate multimodal analyses and longitudinal follow-up to detect delayed deficits and validate therapeutic benefits.