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mise à jour du 3 avril 2003
Acta Neurobiol Exp
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Circadian variation of yawning behavior
Anias J, Homgren B, Urba Holmogren and Eguibar JR
Departementado de investigaciones biomedicas, Universidad de Puebla , Mexico
Tous les travaux de MR Melis & A Argiolas 
Tous les travaux de M Eguibar & G Holmgren


Yawning is a motor pattern widely represented in the behavioraI repertoire among Vertebrates but its physioiogical significance remains obscure. Apart, from its postulated role in social communication in primates and in man , common-place knowledge associates yawning with the transitional phases between sleep and the waking state, or with conditions of physical and mental tiredness. But very few solid facts, if any, stand out in relation to its underlying physiological mechanisms. Behavioral pharmacology has nevertheless opened some leads in that direction. As yawning behavior is elicitable in rats both by cholinomimetic drugs (physostigmine and pilocarpine) or by low doses of apomorphine or other dopamine (DA) agonists, a tentative model of organization of the central mechanisms controlling yawning has been proposed. In this hypothesis two sets of DA and cholinergic (ACh) neurons, localized somewhere in the brain, are supposed to be organized "in series", the former tonically inhibiting the latter, which exert a direct excitatory influence on the central pattern generator (CPG) of yawning. Apomorphine in low doses, by activation of DA presynaptic autoreceptors, induces yawning by disinhibition of the cholinergic excitatory neurons. Higher doses of DA agonists directly inhibit the ACh neurons and thus suppress yawning behavior. As negative and positive modulating influences by noradrenergic (NE) and serotonergic (5-HT) mechanisms on yawning have also been demonstrated, this apparently simple innate behavior seems to be under the control of a complex constellation of neurotransmitter influences.

Being associated to manifestations with so clear circadian rhythmicity as sleep and activity, it is to be expected that yawning should also appear with a circadian rhythm, and justified to try to correlate it with circadian variations in activity, reported in the literature, of the neurotransmitter systems postulated as subserving the central control and regulation of yawning. Diurnal variations in brain levels of ACh, DA, NE and 5-HT, of their biosynthetic or metabolizing enzymes and of their specific receptors have been vastly explored in the last twenty years. The same is true for different behaviors supposed to be under the influence of these particular neurotransmitters, because those behaviors may be induced or modified by proper pharmacolocgical agonists or antagonists. Nevertheless, until 1980, spontaneous and pharmacologically-induced yawning behavior had escaped this detailed scrutiny for diurnal variations. By that time ~Anias~ described that both apomorphine- and physostigmine-induced yawning in Wistar rats presented a clear circadian rhythm. In these rats, kept under a controlled 12 h-12 h light-dark (LD) cycle (lights on at 7 a.m.), pharmacologically--elicited yawning frequency was lowest between 3 and 8 a.m. and showed a high irregular plateau from 10 a.m. to 23 p.m. Due to the very low spontaneous yawning frequency in Wistar rats (below 1 yawn/hour), no circadian variation in this behavior was noticed in absence of pharmacological manipulations.

As some progress has been made in our Animal House in Puebla in the selective breeding of a "high yawning frequency" line of SpragueDawley rats, it is now possible for us to communicate observations on the circadian rhythm of spontaneous yawning.

Our results are based on three groups of young adult male rate, from the F4, F5 and F6 generations, observed during December-January, March-April, and September-October. The first two groups, formed by eight F4 and six F5 animals, were kept and observed in the same laboratory room, under natural illumination (a big 6 ml glass window facing East). They were housed in groups of two or three animals, in transparent acrylic boxes (47 X 43 X 20 cm) containing a layer of wood shavings, covered by a galvanized iron wire top, with a depression to serve as food container and to hold a water bottle. For the observation of yawning during dark hours, the animals were illuminated from the side or from above with a 25 W red lamp placed at approximately 40 cm distance. The animals were manipulated only three times a week, when changed to clean cages. They had ad libitum access to food (standard laboratory rodent pellets) and drinkinc, water. The third group, of six F6 rats, was observed in the Animal House of the C.R.I.R.A. (Centro Regional de Investigaciones en Reproducciôn Animal, Panotla, Tlaxcala, México) where rats were kept under a 14-10 LD schedule, with lights automatically turned on from midnight to 1400, and at an ambient temperature within 19-24'C. This group of rats, when two months old, was accustomed to these new conditions for 25 days before the observation of yawning began.

Yawning occurrence was monitored through the 24 h of the day in twelve to fifteen sessions, irregularly distributed for each group of anirnals over 1 1/2 months. Observation sessions did not last more than two hours, with two observers sitting on opposite sides of the table on which the cages were placed. Observation implied no direct manipulation of the rats, apart from a discrete movement of the boxes on the table, in the first two groups, and carrying them 5 m from a shelf to the table in the third group. These movements of the cages were performed at least 15 min before beginning the clocking of each yawn during the observation period.

The diurnal distribution of yawning frequency (expressed as average yawns/hour) in the two groups-of rats maintained under natural illumination is illustrated in Fig. 2A. Apart from the clear peak shown in the afternoon (late light period), a tendency to exhibit additional lower peaks also seems apparent. When the rats were kept and observed under a 14-10 LD schedule, with artificial illumination and sudden transitions from light to dark (Fig. 2B), the circadian yawning acrophase was displaced in the time of the day, but continued to coincide with the last hour of the light period. This result suggests that the light-to-dark transition might be the "primary synchronizer" of the circadian rhythm of yawning, because the higher frequency of yawns around this time results highly significantly different from a uniform distribution (P < 0.001), using a directional test based on the coefficient of synchronization.

If yawning is a motor pattern under cholinergic activation and subject to DA inhibitory regulation, one might expect that its peak frequency should coincide with hours in the day when cholinergic activity is highest, and dopaminergic activity lowest. It is interesting to note that in two studies in which clear diurnal oscillations of ACh concentrations in the brain have been demonstrated, low levels of the neurotransmitter were measured at the latest part of the light period, coïncident with our observations of maximal yawning frequency. The generaly accepted opinion is that high concentrations of ACh in the brain coincide with low firing rate of the cholinergie neurons, the-1intracellular neurotransmitter being protected from degradation by ACh-esterase. Perhaps even more suggestive are Cahill and Ehret's results on the circadian variation in DA levels, tyrosine hydroxylase activity and turnover rate of dopamine in the rat brain. The lowest turnover rates of DA were calculated for the late light hours. A decrease in dopaminergic activity would, in our hypothesis, liberate the cholinergic neurons exciting yawning from inhibitory control and thus facilitate the expression of this behavioral pattern. Turnover rates of norepinephrine in the brainstem of the rat, also determined by the same authors, show two peaks, at early and late dark period hours, when rats are more active, and according to, our results, yawn more unfrequently than in the last hour before the LD transition.

As some evidence exists in favour of a serotonergic facilitation of pharmacologically-induced yawning, it is important to consider il serotonergic activity may also to the circadian rhythm of spontaneous yawmng. Quay had observed peak 5-HT concentrations in hypothalamus, frontal cortex and lateral portions of the lower brainstem during light hours preceding the LD transition. More recent studies in rats kept in either 12L-12D, or 14L-10D illumination schedules, showed higher 5-HT turnover rates (estimated by 5-HIAA/ 5-HT ratios) during the dark period, when yawning activity is in our experience lower. But as 5-HT rhythms of different shapes take place in different portions of the brain (21, 31), it may not be altogether surprising to encounter difficulties in correlation with a behavioral pattern of which the neuroanatomical structures involved in its control, and regulation are still ignored. On the other hand some doubts exist that total turnover of brain 5-HT may not always reflect the functional serotonergic activity in the brain.

A final quantitative comment. Selective breeding of "high yawning frequency" Sprague-Dawley- rats, in four to six generations, has brought forth an increase in spontaneous yawning frequency to an average (mesor) above 5 yawn/hour, ie, an order of magnitude higher than that observed by us and other authors in Wistar rats. Further analysis of the factors involved in such an important increase in yawning frequency may help in the disclosure of the physiological mechanisms underlying this particular behavioral pattern

Hypothalamic integration of central and peripheral clocks Buijs RM
Apomorphine induced yawning in the rat : influence of fasting and time of day Naselo A