Impact of gestational chlorpyrifos exposure on Attention Deficit Hyperactivity Disorder

The organophosphate Chlorpyrifos (CPF) is classified as a moderately toxic agent that targets the brain and nervous system of organisms, including humans [1-3]. As a pesticide that took off in use en mass since 1965, CPF was most notably used to treat 50 different nut, fruit, vegetable, and cereal crops, alongside turf fields and golf courses [6]. Despite continuing evidence suggesting significant health risks [9-11], a federal ban on CPF usage did not occur until 2021, and the long-term effects of extended exposure remain unknown. Recent evidence indicates that exposure to CPF may increase the risk of developing attention deficit hyperactive disorder (ADHD). Data from our lab shows that noradrenergic fiber density in the cortex, a substrate widely involved in the pathophysiology of ADHD is substantially disrupted in CPF exposed rats. We hypothesize that developmental CPF exposure may be a rodent model for ADHD. Herein, we will investigate the consequences of gestational CPF exposure in the adult by (1) analyzing the effects of gestational day 6-20 CPF exposure on decision making and cortical NE binding in adult rats, (2) determining the effects of selective NE reuptake blockade and NE receptor antagonism on decision making of CPF­ exposed rats, and finally (3) identifying cortical DNA methylation altered by gestational CPF-exposure. These results will provide valuable information to improve our understanding of the long-term consequences of CPF exposure on decision making and LC-NE cortical neurocircuitry, identify possible pharmacological treatment modalities, and determine inheritability of cortical DNA methylation that may predict ADHD-like pathophysiology in subsequent generations.