Changes in EEG power spectra and behavioral states in rats exposed to the acetylcholinesterase inhibitor chlorpyrifos and muscarinic agonist oxotremorine

Abstract

Organophosphates (OPs) inhibit acetylcholinesterase (AChE) activity causing cholinergic stimulation in the central nervous system (CNS). Cholinergic systems are crucial in electroencephalogram (EEG) generation and regulation of behavior; however, little is known about how OP exposure affects the EEG and behavioral states. We recorded EEG, core temperature and motor activity before and after exposure to the OP pesticide chlorpyrifos (CHP) in adult female rats implanted with telemetric transmitters. The recording and reference electrodes were placed in the occipital and frontal bones, respectively. The animals received CHP, 25 mg/kg, p.o., or oxotremorine (OX), 0.2 mg/kg, s.c. CHP led to a significant increase in delta (0.1–3.5 Hz), slow theta (4–6.5 Hz), gamma 2 (35.5–50 Hz), reduction in fast theta (7–8.5 Hz), alpha/sigma (9–14 Hz), beta 1 (14.5–24 Hz), beta 2 (24.5–30 Hz) and gamma 1 (30.5–35 Hz) powers, slowing of peak frequencies in 1–9 Hz range, hypothermia and decrease in motor activity. The drop in 7–14 Hz was associated with cholinergic suppression of sleep spindles. Changes in behavioral state were characterized by dramatic diminution of sleep postures and exploring activity and prolongation of quiet waking. There was recovery in all bands in spite of continued inhibition of AChE activity [44,45] in rats exposed to CHP. OX-induced EEG and behavioral alterations were similar to CHP except there was no increase in delta and the onset and recovery were more rapid. We did not find a correlation between the EEG and core temperature alterations. Overall, changes in EEG (except in delta band) and behavior following CHP were attributable to muscarinic stimulation. Cortical arousal together with increased quiet waking and decreased sleep after CHP occurred independently from inhibition of motor activity and lowering of core temperature.