Sleep-wake disturbances in an animal model of chronic cholinergic insufficiency

Rats reared on a diet in which choline is replaced with N-aminodeanol (NADE), undergo > 50% replacement of brain acetylcholine with acetylated NADE, a false cholinergic transmitter. We examined amounts of sleep and wakefulness in 7 littermate pairs of rats fed either NADE-substituted, or a choline control diet for > 100 days after weaning. During the lights-on portion of the 12/12 h light/dark cycle, NADE rats spent more time awake, and less time in both non-REM and REM sleep compared to littermate controls. Average durations of waking episodes were significantly increased in NADE rats. During the 12 h dark period, there were no between-group differences in sleep-waking amounts. Behavioral hyper-responsiveness which interferes with sleep onset, combined with reduced activity in brainstem cholinergic mechanisms involved in REM sleep generation may underlie daytime sleep-waking disturbances in NADE rats.