# Molecular and Behavioral Impacts of Developmental OP Neurotoxicity

> **NIH NIH R15** · MISSISSIPPI STATE UNIVERSITY · 2021 · $436,465

## Abstract

7. PROJECT SUMMARY/ABSTRACT
Repeated developmental exposure to organophosphorus insecticides (OP) results in long term negative
consequences in children including behavioral problems (ADHD) and decreased cognitive abilities and
motor skills. Animal studies have also identified negative effects following repeated developmental
exposure that persist into adulthood which include altered levels of the synaptic components of of multiple
neurotransmitter systems and behavioral dysfunction. The classical action of OP insecticides is stimulation
of the cholinergic system via the inhibition of brain cholinesterase (ChE). However, environmental
exposures typically occur at levels of an OP that do not induce brain ChE inhibition suggesting a different
mechanism of action. Unfortunately, very few studies have been conducted using exposure levels that did
not inhibit brain ChE. Our previous work demonstrated that repeated developmental exposure to the OP
insecticide chlorpyrifos (CPF), at levels that did not inhibit brain ChE, resulted in significant inhibition of fatty
acid amide hydrolase (FAAH), accumulation of its substrate, the endocannabinoid anandamide (AEA), and
altered emotional reactivity. Our preliminary data identified similar effects in adolescent rats exposed either
to CPF or to a specific inhibitor of FAAH. These included increased adolescent exploratory/anxiolytic and
social behaviors and altered transcriptome and proteome in the amygdala This suggests that inhibition of
FAAH is responsible for many of the persistent effects induced by developmental OP exposure. This
application's objective is to further characterize how OP-mediated developmental FAAH inhibition alters
behavior and neurochemistry in adolescence. The observed increased exploratory/anxiolytic behavior
suggests that developmental OP exposure could alter other behaviors including attention, impulsivity, and
risk-related behavior which are behaviors reported to be altered in children exposed to OPs. This will be
determined in Aim 1. The developmental inhibition of FAAH results in transcriptomic/proteomic changes
suggesting altered synaptic components of the GABAergic and glutamatergic systems with tendency
towards GABAergic signaling. The presence of this will be tested in Aim 2. Overall, these studies dive more
deeply into this newly recognized mechanism by attempting to further dissect the components involved and
establish a clearer understanding of the persistent outcomes that are directly connected to the binding of
the OP to the target.

## Key facts

- **NIH application ID:** 10202963
- **Project number:** 1R15ES032959-01
- **Recipient organization:** MISSISSIPPI STATE UNIVERSITY
- **Principal Investigator:** Russell L Carr
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $436,465
- **Award type:** 1
- **Project period:** 2021-05-05 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202963

## Citation

> US National Institutes of Health, RePORTER application 10202963, Molecular and Behavioral Impacts of Developmental OP Neurotoxicity (1R15ES032959-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10202963. Licensed CC0.

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