Sleep. 14(2):116-120 © 199 I Association of Professional Sleep Societies Effects of Sleep Deprivation on Sleepiness and Increased REM Sleep in Rats Selectively Bred for Cholinergic Hyperactivity *Priyattam 1. Shiromani, *lavier Velazquez-Moctezuma, tDavid Overstreet, *Mark Shalauta, *Sam Lucero, and *Cheryl Floyd *Department of Psychiatry (V-116A), San Diego VA Medical Center, and University of California, San Diego, La Jolla, California 92161, U.S.A.; and tSchool of Biological Sciences, Flinders University, Bedford Park, South Australia 5042, Australia Summary: In this study we employed a modification of the multiple sleep latency test (MSLT) to determine whether rats of a strain with increased cholinergic activity were sleepier compared to randomly bred control rats. Seven rats each from the Flinders sensitive line (FSL, hypercholinergic) and Flinders resistant line (FRL, age- matched controls) were kept awake for 20 min and then allowed to sleep ad libitum for 20 min. The regimen of 20 min of wakefulness followed by 20 min of sleep was repeated 12 times during the day. There were no differences in latency to sleep or to rapid eye movement (REM) sleep or in percent total sleep time, drowsy, or slow-wave sleep between FSL rats and FRL rats. However, FSL rats showed a significant increase in REM sleep compared to FRL rats. This selective increase in REM sleep may be coupled to an increase in brain muscarinic receptors in the FSL rats. Key Words: Sleep-REM sleep-Acetylcholine-Narcolepsy-Depression-Hypercholinergic. Recently, a line of rats that display increased central cholinergic sensitivity has been developed. The Flin- ders sensitive line (FSL) rats were developed by tively breeding rats showing a large hypothermic response to the irreversible anticholinesterase, diiso- propyl fluorophosphate (DFP)(l). Compared to ran- domly bred controls or age-matched rats showing a small hypothermic response to DFP (Flinders resistant line- FRL) , FSL rats show increased concentrations of muscarinic receptors in the striatum and hippocam- pus (2,3). No changes were found in levels or turnover of acetylcholine (ACh) in these brain regions. These data suggest that the increased cholinergic activity in FSL rats is derived from postsynaptic receptor mech- anisms rather than from changes at the presynaptic level. Considering the link between the cholinergic system and rapid eye movement (REM) sleep (4), we exam- ined the sleep patterns and found that FSL rats exhib- ited a 35% increase in REM sleep compared to FRL rats (5). The FSL rats also entered into REM s1e:ep Accepted for publication July 1990. Address correspondence and reprint requests to Priyattam J. Shi- romani, Research (151C), VA Medical Center, 940 Belmont Street, Brockton, MA 02401, U.S.A. from drowsy sleep more often and their interval be- tween REM sleep episodes was significantly shorter. In order to further investigate sleep in these rats we used a modification of the multiple sleep latency test (MSLT) to determine whether 20-min periods of sleep deprivation would reveal greater changes in sleep pa- rameters in the FSL rats compared to FRL controls. The MSLT is used in humans to assess sleepiness and the presence of abnormal sleep-onset REM sleep epi- sodes (6,7). METHODS Ninety-day-old male FSL and FRL rats derived from the breeding colony at San Diego and weighing about 400 g were used in this study. Seven FSL and seven FRL rats were each implanted under anesthesia with cortical screw electrodes to record electroencephalo- graphic (EEG) activity, and flexible wires were sewn into the nuchal muscles to record electromyographic (EMG) activity. Since initial selection and derivation from Sprague-Dawley rats, FRL rats have been main- tained by selectively breeding successive generations of rats which showed a small hypothermic response to the cholinergic agonist oxotremorine. FSL rats, on the other hand, were derived by mating rats showing 116 Downloaded from https://academic.oup.com/sleep/article/14/2/109/2742769 by guest on 16 December 2022