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1 novembre 2001
Yawning as an aura for an L-Dopa induced "on" in Parkinson's disease
JL Goren JH Friedman
Memorial Hospital of Rhode Island Pawtucket USA
A trial of subcutaneously injected apomorphine for parkinsonian
reponses in Yawning in Parkinson's disease Colosimo C, F Evidente...
Friedman JH. Yawning, or Not Having Enough To Do. Medicine & Helath Rhode Island. 2012;95(8):234

Yawning is a poorly understood phenomenon that occurs in humans as well as most vertebrates(1). Yawns are slow, involuntary gaping movements of the mouth that begin with a slow inspiration and end with a larger expiration (1). They are frequently but not always associated with stretching (1). Yawning bas been associated with boredom, fatigue, sleepiness, a variety of pathologie states, and many drugs. Dopamine agonists and cholinergic agonists induce yawning (2,4) whereas cholinergic receptor antagonists and dopamine antagonists block this effect (5).

As best we could determine, yawning has not been associated with treated or untreated Parkinson's disease (PD). Since biochemical and pharmacologic evidence points to a central role for cholinergic and dopamaminergic mechanisms, the occurrence of yawning in treated PD patients may shed light on this poorly understood, although possibly unimportant, phenomenon. We were impressed by one patient's story-that his "ons" were always preceded by yawns although he was feeling neither sleepy nor more alert. A second patient also volunteered a similar yawning experience. We report this phenomenon mostly for its theoretical interest for the understanding of yawning.

Patient report : A 58-year-old man was diagnosed with PD at age 44. He has been treated with carbidopa-levodopa since age 47. Clinical fluctuations in response to L-dopa began at age 50. Trials of pergolide, bromocriptine, and amantadine were net tolerated. Sinemet controlled release induced worsening dyskinesias. When "on" the patient had good mobility and walked independently. When "off" he could not get up from a chair, tap his feet when seated, or walk. He reported that the yawning bad been an aura for turning "on" from L-dopa since the age of 54. The yawns always preceded turning "on," but voluntary yawning did not induce air "on." The yawning generally preceded turning "on" by 3 to 6 minutes and was often associated with stretching. At the time when his yawning was observed he was taking carbidopa-levodopa 25/ 250 one-half tablet every 60 to 90 minutes throughout the day and most of the night. His last dose had been about 15 minutes before. He took no other medications. He was mobile for about 2 hours in the morning, 2 hours in the afternoon, and 1 hour at night. He was observed in the "off" state, unable for move his legs or to walk. He yawned, without stretching, and denied sleepiness or change in his level of alertness. About 5 minutes later he suddenly turned "on," and was able to stand easily and walk without difficulty. No dyskinesias were present.


Yawning is considered a primitive behavior associated with changes in arousal levels, with most yawning taking place during transitions from sleeping to waking and from wakin. An increase in yawning is a reliable predictor of achange in arousal levels (6). However, yawning may be only one of many mechanisms that cause a change in level of alertness and may simply be a marker of the change (an epiphenomenon) or a mechanism to maintain some level of activity(1,6).

The physiologic mechanism of yawning is poorly understood. Anencephalics, having only a brainstem and rudimentary midbrain structure, still yawn, thus indicating that some neural circuits necessary for yawning are most likely near the respiration center in the medulla. The neural mechanism probably involves both respiratory and motor components, because hemiplegics are unable to separate these acts. In fact, hemiplegics may perform involontary stretching movements of their otherwise paralyzed arm while yawning. Lesion experiments suggest that the Striatum is critically involved in the yawning process. Apomorphine when administered directly into the caudate nucleus and the paraventricular nucleus, induces yawning, suggesting that a central dopaminergic system may be related to yawning(2,4).

Based on experimental findings, the yawning induced by cholinesterase inhibitors and moscarinic receptor agonists involves cholinergic activation alone. The yawning responses to dopamine receptor agonists.- on the other hand, seem to require both dopaminergic and cholinergic activation, because muscarinic receptor antagonists block yawning induced by both dopamine and cholinergic agonists, whereas dopamine receptor antagonists block only yawning induced by dopamine agonists(5).

However, the pharmacology is far more complicated than this. Various neuropeptides, such as alpha melanocyte stimulating hormone and oxytocin, will induce yawning when injected into rat ventricles (7) This is increased by pretreatment with pindolol, a ß-adrenoreceptor antagonist, although pindolol does itself induce yawning. Oxytocinpindolol yawning is blocked by scopolamine, an anticholinergic, but not by spiperone, a dopamine-type receptor blocker(5) In addition, a wide variety of drugs produce yawning, as well as some drug withdrawal syndromes.

If yawning is a dopamine-mediated phenomenon in humans it should be seen in PD patients treated with L-dopa and dopamine agonists. The occurrence of the yawn is clearly a transient phenomenon, signaling a change of state (always "off" to "on"), but was not associated with a change in level of arousal, at least as perceived by the patients or by one author (JHF). Our observations may lead to further understanding of yawning, which may hopefully have an impact on our understanding of the dopamineacetylcholine systems in PD.

Address correspondence and reprint requests to Dr. Joseph H. Friedman. Memorial Hospital of Rhode Island


  1. Provine R. Yawning. In: Carskadon MA, ed, Encyclopedia of sleep and dreaming. New York: McMillan press, 1993:651-654
  2. Melis MR, Stancampiano R, Argiolas A. Hippocampal oxytocin mediates apomorphine-induced penile erections and yawning. Pharmacol Behav 1992;42:61-66.
  3. Zarrindast MR, Toloui V, Hashemi B Effect of GABAergic drugs on physostigmine-induced yawning in rats. Psychopharmacology (Berl) 1995: 122:297-300.
  4. Zarrindast MR, Fatehi F, Mohagheghi-Badi M. Effects of adenosine agents on apomorphine-induced yawning in rats. Psychopharmacolog. (Berl) 1995;122:292-296.
  5. Protais P, Dubuc I, Constentin J. Pharmacological characteristics of dopamine receptors involved in dual effects of dopamine agonists on yawning behavior in rats. Eur J Pharmacol 1983,94:271-280.
  6. Baenninger R. Binkley S, Baenninger M. Field observations of yawning activity in humans. Physiol Behav 1996;59A21-425.
  7. Fujikama NI, Yiamada K. Nagashima M. Furukawa T. Involvement of adrenoreceptors in regulation of the yawning induced by neuropeptides, oxytocin and alpha-melanocyte stimulaing hormone in rats. Pharmacol Biochem Behav 1995:503:339-343.