Nature 274, 490 - 492 (03 August 1978); doi:10.1038/274490a0

Experimental acceleration and slowing of REM sleep ultradian rhythm by cholinergic agonist and antagonist

N. SITARAM, ANGELA M. MOORE & J. CHRISTIAN GILLIN

Biological Psychiatry Branch, Unit on Sleep Studies, National Institute of Mental Health, Bethesda, Maryland 20014
Laboratory of Clinical Psychopharmacology, St Elizabeth's Hospital, NIMH Washington, DC 20032

MAMMALIAN sleep is characterised by the cyclical occurrence of rapid eye movement (REM) and non-REM sleep. In humans, REM sleep (consisting of a desyncronised electroencephalogram (EEG), rapid eye movements, atonic electromyogram (EMG), and usually accompanied by dreaming), occurs every 90−110 min¹ and is presumed to be under the control of an underlying ultradian oscillatory mechanism². The biological basis of the above ultradian rhythm is unknown. Although in humans the amount of REM sleep itself can be experimentally increased³⁻⁶ or decreased⁷⁻⁹ by pharmacological and physiological means, none of these manipulations has been shown to alter the frequency of its presumed oscillator. We demonstrate here that a normal 104-min REM sleep ultradian rhythm can be experimentally shortened to a 56-min rhythm by repeated infusions of arecholine, a cholinergic muscarinic agonist¹⁰. Conversely, scopolamine, a cholinergic muscarinic antagonist¹¹, prolonged the interval between successive REM periods. We speculate that acetylcholine may have a specific role in the timing of the ultradian oscillatory mechanism controlling REM sleep.

References

1.	Dement, W. C. & Kleitman, N. Electroencephalogr. clin. Neurophysiol. 9, 673–690 (1957).
2.	Kripke, D. F. in Advances in Sleep Research (ed. Weitzman. E. D.) 1, 305–325 (Spectrum, Flushing, 1974).
3.	Hartman, E. Psychopharmacologia 9, 242–247 (1966).
4.	Wyatt, R. J., Zarcone, V., Engelman, K., Dement, W. C., Snyder, F. & Sjoerdsma, A. Electroencephalogr. clin. Neurophysiol. 30, 505–509 (1971).
5.	Oswald, I., Thacore, V. R., Adam, K., Brezinova, V. & Burack, R. Br. J. clin. Pharmac. 2, 107–110 (1975).
6.	Torda, C. N.Y. State J. Med. 68, 1135 (1968).
7.	Gillin, J. C., Post, R. M., Wyatt, R. J., Goodwin, F. K., Snyder, F. & Bunney, W. E., Jr Electroencephalogr. clin. Neurophysiol. 35, 181–186 (1973).
8.	Mendelson, W. B., Reichman, J. & Othmer, E. Biol. Psychiat. 10(4), 459–464.
9.	Sagales, T., Grill, S. & Domino, E. F. Clin. pharmac. Ther. 10, 522–529 (1969).
10.	Baker, R. W., Chothia, C. H., Pauling, P. & Petcher, T. J. Nature 230, 439–445 (1971).
11.	Safer, D. J. & Allen, R. P. Biol. Psychiat. 3, 347–355 (1971).
12.	Sitaram, N., Mendelson, W. B., Wyatt, R. J. & Gillin, J. C. Brain Res. 122, 562–567 (1977).
13.	Rechtschaffen, A. & Kales, A. A Manual of Standardized Terminology, Technique and Scoring System for Sleep State of Human Subjects (Department of Health, Education, and Welfare, Washington, DC, 1968).
14.	Moses, J., Lubin, A., Johnson, L. C. & Naitoh, P. Nature 265, 360–361 (1977).
15.	Sitaram, N., Moore, A. M. & Gillin, J. C. Sleep (in the press).
16.	Hobson, J. A., McCarley, R. W. & Wyzinski, P. W. Science 189, 55–58 (1975).
17.	Feinberg, I. J. psychiat. Res. 10, 283–306 (1974).