Balance the Forces of Sleep

Understanding Cholinergic Sleep

A new study has found that administration of the serotonin precursor 5-hydroxytryptophan (5-HTP) to adult male hamsters increased both rapid-eye-movement (REM) sleep - a type of sleep related to increased memory performance - and total sleep time.1 This is good news for those who have difficulty sleeping, as is often the case as we age. In fact, along with lower energy levels, inadequate sleep is one of the major complaints related to aging. The two are interrelated.

In the study, methysergide, a drug that stimulates serotonin receptors, facilitated REM sleep, and physostigmine, a drug that inhibits the breakdown of acetylcholine (thereby increasing acetylcholine levels), increased REM sleep without altering the total sleep time. Not surprisingly, the coadministration of these two drugs increased the amount and frequency of REM sleep. By contrast, atropine, a drug that inhibits acetylcholine receptors, made REM sleep disappear, both in the absence and presence of 5-HTP.

This study is highly suggestive that the serotonergic (serotonin-mediated) system involved in REM sleep is regulated by cholinergic (acetylcholine-mediated) receptor activity. While the role of serotonin in sleep has been well established, acetylcholine's participation in this process has not been widely recognized. Yet the cholinergic system is believed to induce and maintain REM sleep. In this regard, acetylcholine may also serve to induce a state of "sleep vigilance" for stimuli that are worth waking up for (the cries of a child, e.g.), while simultaneously acting as a kind of sleep sentry, allowing the "sleeping" mind to distinguish between messages of alarm and the innocuous noises of the night.

Thus, with adequate acetylcholine, the mind is better able to filter out extraneous sounds and other disruptive stimuli. This acetylcholine-assisted filtration mechanism prevents interruptions of sleep by stimuli that are not legitimate triggers for arousal. During sleep, the cholinergic system mediates the transition of states from deep to light sleep, to permit arousal as the occasion warrants.2 While undoubtedly there are reciprocal interactions between cholinergic and adrenergic/serotonergic systems, i.e., it's more complicated (as one would expect) than just cholinergic, acetylcholine is very important. In its role as the guardian of sound sleep, it protects us from awakening with every draft, creak, or murmur - or our spouse's rolling over. Because choline is the primary precursor of acetylcholine, supplemental amounts of this nutrient can help prevent the nonessential disruption of sleep.

It should be possible to sleep well without drugs. What may help is 5-HTP, the precursor of serotonin, as well as choline and vitamin B5, the precursor and cofactor, respectively, of acetylcholine; also the natural hormone melatonin and the herb valerian. These ingredients support proper serotonergic function as well as proper cholinergic function, and so should be supportive of rejuvenating sleep, which helps maintain the body's internal clock. Melatonin and valerian have multiple roles in this regard, including shortening the time needed to fall asleep and improving sleep vigilance.3 (See Goodnight, SleepTight™ – Sep. 1999.)

Melatonin also seems to regulate the tone of cerebral arteries, firming and tightening their structure.4 Last but not least, because acetylcholine is associated with muscle tone, an adequate supply can help strike a balance between contractile (too tight) and relaxing (not tight enough) factors. Because proper muscle tone has been found to play a role in REM sleep,5 these mechanisms lend new meaning to the phrase "sleep tight."


  1. Guha M, Biswas S, Poddar MK. Possible involvement of central cholinergic-serotonergic interaction in natural sleep. Methods Find Exp Clin Pharmacol 1988 Apr;10(4):243-5.
  2. Koyama Y, Imada N, Kayama Y, Kawauchi A, Watanabe H. How does the distention of urinary bladder cause arousal? Psychiatry Clin Neurosci 1998 Apr;52(2):142-5.
  3. Houghton PJ. The scientific basis for the reputed activity of valerian. J Pharm Pharmacol 1999 May;51(5):505-12.
  4. Bubenik GA, Blask DE, Brown GM, Maestroni GJ, Pang SF, Reiter RJ, Viswanathan M, Zisapel N. Prospects of the clinical utilization of melatonin. Biol Signals Recept 1998 Jul-Aug;7(4):195-219.
  5. Kodama T, Lai YY, Siegel JM Enhanced glutamate release during REM sleep in the rostromedial medulla as measured by in vivo microdialysis. Brain Res 1998 Jan 5;780(1):178-81.

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