haut de page

mise à jour du 11 juillet 2002
2000; 41; 178-180
Yawning: an evolutionary perspective
 Effect of time-of-day on the yawning response to apomorphine in normal subjects
Samarthji Lal, Y.Tesfaye, J.X.Thavundayil, A.Skorzewska, G.Schwartz
Douglas Hospital Research Center, Verdun, and Department of Psychiatry, Montreal General Hospital, Montréal, Québec, Canada
A trial of subcutaneously injected apomorphine for parkinsonian
Introduction: Apomorphine (Apo), a dopamine (DA) receptor agonist in animals and man, induces yawning in a variety of species including humans, by stimulating central D2 receptors. Systematic studies of Apo-induced yawning in man have been few. As a result of unexpected circumstances, we were obliged to change the time of our experiments on yawning from the morning to the afternoon. On inspection of our findings, we observed that when Apo was given in the aftemoon, the yawning response was less. We now report our results.

Materials and Methods : Subjects : Two separate groups of normal male volunteers on no medication who were physically healthy, based on medical history, physical examination, routine biochemical screening, hemogram, urinalysis and ECG, and who gave their informed consent served as subjects. All volunteers were asked to keep their sleep habits and their caffeine intake constant at least 2 weeks prior to commencing the study. Shift workers were excluded. Subjects were asked to refrain from over-thecounter drugs such as aspirin as well as alcohol for at least 72 h prior to testing. Subjects using recreational drugs were excluded. The ApoAM group, who were investigated in the morning, consisted of 11 men (mean age 25.5. range 19-31 vearsland the Apo-PM group, who were investigated in the afternoon, consisted of 16 men (mean age 27.6: range 20-35 years).

Procedures : Subjects were informed that they would be tested on three separate occasions. and that on two of these they would receive placebo (physiological saline) and on one occasion Apo HCI (7 pg/kg s.c.). The first session. conducted under single blind conditions, was an adaptation session in which the subjects received placebo. Data from this session were discarded. The remaining two sessions were conducted under double-blind conditions in a balanced design. The Apo AM group arrived at the laboratory after an overnight fast between 8.00 h and 8.30 h. Following attachment of the sensors, one to the forchead just below the hairline and the other under the chin. the subjects rested quietly in the supine position for 30 min. Apo or placebo were administered at 9.00 h. The Apo-PM group arrived ai the laboratory between 12-00 h and 12.30 h. They were allowed to eat breakfast but fasted after 9.00 h. After resting supine for 30 min Apo or placebo was administered at 13.00 h. Following injection, yawning was monitored over a 60-min period with a polygraph by recording displacement of the lowerjaw using a pair of linearized magnetometers as described previously.

Data Analysis : Yawns were identified by inspection of the tracing by two independent raters blind to the treatment code. The yawns were readily distinguished from swallowing, coughing and sneezing, and there was complete concordance between the raters. The number of yawns were tallied and differences between treatments and between groups were analyzed using the Mann-Whitney test for unpaired data and the Wilcoxon sign-rank test for paired data. Data are presented as the mean ± standard deviation (SD).

Results : Apo increased yawning when given in the morning: Apo-AM 18.3 ± 12.5 (mean ± SD) versus placebo-AM 10.7 ± 8.5 (p < 0.02). In contrast, Apo administration in the afternoon showed no significant increase versus placebo: Apo-PM 6.1 ± 5.9 versus placebo-PM 4.1 ± 4.1 (p = NS). The number of yawns after Apo in the morning was significantly greater than after Apo given in the afternoon (p < 0.01). Placebo-induced yawning was significantly greater in the morning than in the afternoon (p < 0.025). When the placebo response was subtracted from the Apo response for each individual, the morning-afternoon difference after Apo remained significant (p < 0.02).

Discussion : Yawning is under the control of several neurotransmitters and neuropeptides subserved by different neural mechanism. Yawning induced by Apo is mediated by activation of central D2 receptors located in the paraventricular nucleus of the hypothalamus which contains nerve endings from the incertohypothalamic DA system. Nitric oxide formation may be involved in the process as an intracellular messenger. Central muscarinic and oxytocinergic links are important mediators of Apo effects. Activation of D 1 receptors has a facilitatory role. DA autoreceptors have been implicated in the yawning response but more recent evidence points to the stimulation of postsynaptic DA receptors in both animals and man.

In the rat, there is a circadian variation in tyrosine hydroxylase activity, DA turnover, DA levels and number of DA receptors. A change in receptor number could explain our present rindings of a difference in yawning response depending on time of day of Apo administration. In the rodent, a time-of-day effect on the yawning response to Apo has been described which is linked to the light-dark cycle. This diurnal variation is also noted with spontaneous yawning.

In the rat, fasting for 24 h influences Apo-induced yawning. In the present study, both groups of men were fasting, but the Apo-AM group fasted longer. Accordingly, this difference may have influenced our findings. In the rat, fasting decreases the yawning response to Apo. However, the influence of fasting on yawning in man is unknown. Our results show an increase in yawning in subjects tested in the morning, ie. those fasting longer. Constant stress and intermittent stress differentially affect Apo-induced yawning in the rat. The response is also influenced by paradoxical sleep deprivation. The influence of such factors in man is unknown. The yawning response to both Apo and placebo decreases with age. In the present study, there was no significant difference in age between the two groups of subjects.

In man, psychological factors such as boredom, lack of stimulus interest, suggestion induced by observing, reading and thinking about yawning may induce yawning. Baenninger, however, found little influence of boredom and contagiousness of yawning. Recently, Baenninger et al. showed that yawning frequency was unrelated to the prior amount of sleep, times of awaking or retiring, but was consistent with the view that yawning is predictive of an increase in activity level. The response to placebo under experimental conditions noted previously and confirmed in the present study indicates that suggestion plays some role in spontaneous yawning. It is possible that subjects tested in the morning were more drowsy and hence the increase in yawning. Though tiredness and drowsiness have anecdotally been associated with yawning, a relationship between drowsiness and yawning frequency has not been observed experimentally. In a field study of taxi drivers Sakai and Takashi reported an increase in yawning burst especially when the subjects were feeling drowsy. Drowsiness, however, was not quantified.

  1. Lal S, Tesfaye Y, Thavundayil JX, Skorzewewska A, Schwartz G Effect of time-of-day on yawning response to apomorphine in normal subjects Neuropsychobiology 2000; 41(4): 178-180
  2. Lal S, Grassino A, Thavundayil JX, Bubrovsky B A simple method for study of yawning in man induced by the dopamine receptor agonist, apomorphine. Progr Neuropsychopharmacol Biol Psychiatry 1987; 11; 223-228
  3. -Lal S, Y Tesfaye et al Apomorphine: clinical studies on erectile impotence and yawning. Prog Neuropsychopharmacol Biol Psychiatry (1989) 13(3-4): 329-39
  4. -Tesfaye Y, Lal S Hazard of yawning Canadian Med Assoc J 1990;142;1;p15
  5. -Tesfaye Y, Lal S, Skorzewska A Hazard of yawning Canadian Med Assoc J 1991;145;12;p1560
  6. -Skorzewska A, Tesfaye Y , Krishnan B, Schwartz G, Thavundayil J, Lal S Effect of scopolamine on spontaneous yawning in men. Neuropsychobiology 1993;27(1):17-20
  7. -Lal S Apomorphine in the evaluation of dopaminergic function in man Prog Neuropsychopharmacol Biol Psychiatry 1988; 12(2-3): 117-64
  8. Lal S, Thavundayil JX, Ng Ying Kin NM, Dai X, Schwartz G, Montoya A. Induction of tolerance of dopaminergic responses in man. J Neural Transm. 2008