Chronic, low-level exposure to the cholinesterase inhibitor DFP. II. Time course of behavioral state changes in rats

Rats were repeatedly administered with low doses of diisopropylfluorophosph ate (DFP; 0.2 mg/kg/day, SC), an irreversible cholinesterase (ChE) inhibito r. Control rats received a daily injection of oil vehicle or of saline. Rec ordings 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 tr eatment. DFP administration increased waking at the expense of slow-wave sl eep (SWS), but not of paradoxical sleep (PS); as a result, the PSI SWS rati o 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 pa ralleled the time course of ChE inhibition in the mesopontine cholinergic n uclei and the pontine reticular formation described in the companion articl e. In contrast, after DFP withdrawal, behavioral states returned to control values more rapidly tin 2-4 days) than did ChE activity. These results are discussed regarding the promoting role of cholinergic neurotransmission in brain-activated states. (C) 1999 Elsevier Science Inc.