Chronic, Low-Level Exposure to the Cholinesterase Inhibitor DFP. II. Time Course of Behavioral State Changes in Rats

Abstract

Rats were repeatedly administered with low doses of diisopropylfluorophosphate (DFP; 0.2 mg/kg/day, SC), an irreversible cholinesterase (ChE) inhibitor. Control rats received a daily injection of oil vehicle or of saline. Recordings of the sleep–wake states were obtained in the 6 h following 1, 3, 6, 9, 13, 17, and 21 injections, as well as 2, 4, and 19 days after 9-day treatment. DFP administration increased waking at the expense of slow–wave sleep (SWS), but not of paradoxical sleep (PS); as a result, the PS/SWS ratio was strongly enhanced. These changes developed across days, were maximal after six to nine injections, and were then maintained at that level until cessation of treatment. This time course of behavioral state alterations paralleled the time course of ChE inhibition in the mesopontine cholinergic nuclei and the pontine reticular formation described in the companion article. In contrast, after DFP withdrawal, behavioral states returned to control values more rapidly (in 2–4 days) than did ChE activity. These results are discussed regarding the promoting role of cholinergic neurotransmission in brain-activated states.