mystery of yawning
Le bâillement, du réflexe à la pathologie
Le bâillement : de l'éthologie à la médecine clinique
Le bâillement : phylogenèse, éthologie, nosogénie
 Le bâillement : un comportement universel
La parakinésie brachiale oscitante
Yawning: its cycle, its role
Warum gähnen wir ?
Fetal yawning assessed by 3D and 4D sonography
Le bâillement foetal
Le bâillement, du réflexe à la pathologie
Le bâillement : de l'éthologie à la médecine clinique
Le bâillement : phylogenèse, éthologie, nosogénie
 Le bâillement : un comportement universel
La parakinésie brachiale oscitante
Yawning: its cycle, its role
Warum gähnen wir ?
Fetal yawning assessed by 3D and 4D sonography
Le bâillement foetal
The yawning elicited by alpha-melanocyte-stimulating hormone involves serotonergic-dopaminergic-cholinergic neuron link in rats
K Yamada, T Furukawa
Dopamine agonist-induced yawning in rats: a dopamine D3 receptor mediated behavior
Collins G et al
Sleep-wakefulness, EEG and behavioral studies of chronic cats without neocortex and striatum: the "diencephalic" cat
Villablanca J, Marcus R
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3 juillet 2003
Oxford Science Publications
Neural basis of drug induced yawning
In Neurobiology of stereotyped behaviour
Cooper Steven J, Dourish Colin T
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In a study of human yawning Robert Provine (1986) remarked that yawning is a prominent stereotyped action pattern and releasing stimulus which "does not deserve its current status as a minor behavioural curiosity". Indeed, "yawning may have the dubious distinction of being the least understood, common, humnan behaviour". In contrast, a large body of experimental data has been collected during the past 30 years on drug-induced yawning in animals (particularly rodents). In this chapter we consider the neural basis of drug-induced yawning in rodents and discuss the relevance of this pharmacological phenomenon to "spontaneous" yawning in animals and man.
We propose that yawning rmay be controlled by a complex interaction of catecholaminergic, serotonergic, and peptidergic neuronal mechanisms. A model is put forward to explain how yawning may be caused largely by peptidergic and cholinergic excitation and dopaminergic inhibition. Furthermore, we present evidence which suggests that, in animals and man, yawning may be a marker of recovery from acute stress and that these responses may be closely associated with an inhibition of brain dopamine metabolism. [...]
Interaction of brain dopaminergic, cholinergic, and peptidergic neurones in the mediation of yawning: an hypothesis and a model
It is clear from the preceding pages that yawning behaviour is influenced by a number of interacting; neurotransmitter systems. Major influences are exerted by brain dopaminergic, cholinergic, and peptidergic neurones and in this section we propose a hypothesis which explains how these various neurotransmitter mechanisms may interact to control yawning and associated behaviours.
There is strong evidence for the involvement of dopaminergic inhibition and cholinergic excitation in yawning. Thus, yawning induced by dopaminergic drugs is probably caused by activation of dopamine autoreceptors (or inhibitory postsynaptic dopamine receptors) which reduces dopamine synthesis and release. In contrast, yawning induced by cholinergic agents appears to be due to increased release of acetylcholine and stimulation of postsynaptic muscarinic receptors.
In cross-blocking studies, it bas been shown that dopamine agonist induced yawning; is attenuated or abolished by treatment with muscarinic receptor antagonists (Yamada and Furukawa 1980, 1981; Holmgren and Urba-Holmgren 1980). In contrast, dopamine antagonists potentiate yawning induced by physostigmine (Yamada and Furukawa 1980; Holmgren and Urba-Holmgren 1980). Therefore, these authors have proposed that yawning is produced by the release of cholinergic neurones from tonic dopaminergic inhibition. This disinhibition may be caused by activation of dopamine autoreceptors at presynaptic neuronal sites induced by low doses of dopamine agonists. Thus, the same functional effect (ie. increased yawning) is produced by stimulation of postsynaptic cholinergic receptors or presynaptic (inhibitory) dopamine receptors. Blockade of postsynaptic dopamine receptors by a dopamine antagonist would also activate cholinergic neurones and this probably accounts for the potentiation of physostigmine-induced yawning by neuroleptics (Yamada and Furukawa 1980).
It seems that the striaturm may be the central locus for this dopaminergic-cholinergic neuronal interface. The striatum in the rat receives innervation from approximately 3500 dopaminergic neurones located in the zona compacta of the substantia nigra (Andén et al. 1964, 1966). The terminals of these dopamine neurones make synaptic connections with striatal interneurones (which represent the majority of striatal neurones) and neurones which innervate the substantia nigra and globus pallidus. Acetylcholine is a major striatal transmitter and most of it is located in interneurones (Hassler 1978). The dopaminergic nigrostriatal neurones make synaptic contact with these cholinergic neurones (Hattori et al. 1976) and inhibit their firing (Roth and Bunney 1976; Trabucchi et al. 1975). In contrast, there is no apparent dopaminergic-cholinergic link in other major dopamine terminal regions such as nucleus accumbens and olfactory tubercles (Ladinsky et al. 1975).
In yawning experiments, it has been shown that the striatum is very sensitive to dopamine agonist treatments and that 6-OHDA lesions of the striatum. or substantia nigra abolish yawning induced by a small dose of apomorphine (Dourish et al. 1985; Dourish and Hutson 1986; Stoessl et al. 1987). Furthermore, yawning induced by intrastriatal injection of piribedil is abolished by blockade of either dopamine autoreceptors (with low-dose haloperidol) or postsynaptic muscarinic receptors (with scopolamine) (Dourish et al. 1985). At this point, our yawning model comprises striatal cholinergic excitation and dopaminergic inhibition. We noted earlier that the peptide hormones ACTH, a-MSH, beta-LPH and oxytocin are potent yawning inducers. Therefore, the question arises as to how peptidergic mechanisms interact with neuronal dopamine and acetylcholine to control yawning.
There is evidence that ACTH and alpha-MSH injection can activate cholinergic neurones (Torda and Wolff 1952; Marx 1975). Accordingly, yawning induced by ACTH and alpha-MSH is paralleled by a twofold elevation of acetycholine turnover in hippocampus (Wood et al. 1978). This is consistent With evidence that peptide-induced yawning is suppressed by cholinergic antagonists and neuroleptics (Ferrari et al. 1963; Yamada and Furukawa 1981). These data suggest that yawning is associated with cholinergic and peptidergic excitation and dopaminergic inhibition.
Indeed it is known that alpha-M S H-producing cells in the pituitary are under the inhibitory control of dopaminergic neurones originating from the arcuate nucleus of the hypothalamus (Tilders and Smelik 1977). Therefore, it is possible that inhibition of dopamine release (caused by low-dose dopamine agonist treatment) may indirectly result in release of newly synthesized peptides (ACTH, alpha-M S H, betaLPH, oxytoxin) from the pituitary or from peptidergic neurones (Serra et al. 1983a).
The importance of the pituitary in mediating yawning is illustrated by the observation that hypophysectomy prevents yawning induced by apomorphine (Serra et al. 1983a). Similarly, apomorphine-induced yawning is prevented by treatment with the protein synthesis inhibitor cycloheximide (Serra et al. 1983b).
The observation of Wood et al. (1978) that ACTH and alpha-MSH specifically increased acetylcholine turnover in the hippocampus indicates that this brain region may be of importance in the control of yawning. This idea is supported by evidence from lesion studies in which it has been demonstrated that partial ablation of the hippocampus potentiates ACTH-induced yawning whereas total hippocampectomy abolishes the response (Colbern et al. 1977). This study also implicated the amygdala and the mammillary bodies in the control of yawning since lesions in these areas modified the response to ACTH.
Interestingly, lesion studies have also enabled the differentiation of the yawning and sexual arousal components of the ACTH-induced syndrome. Thus, pre-optic lesions, destroying structures which take up labelled testosterone, abolished penile grooming and erection but did not affect yawning (Bertolini et al. 1975).
The model we propose to explain the neural control of yawning is illustrated in Fig. 4.7. It is clear that there are cholinergic, peptidergic, serotonergic (all excitatory), dopaminergic, and noradrenergic (both inhibitory) inputs to the system. At this point it is unclear whether the final step in the pathway is peptidergic or cholinergic. However, it is noteworthy that all of these influences may precede a mechanism illustrated on the bottom right portion of Fig. 4.7. Cortical spreading depression was shown to produce yawning and sexual arousal by Huston (1971). In a subsequent study, Jakobartl and Huston (1977) observed that intracranial injection of ACTH produced spreading depression and that the hippocampus was more sensitive to the peptide than the cortex. Thus, it is possible that yawning and related behaviour elicited by ACTH could be secondary to hippocampal spreading depression.
In this chapter we have described how drug-induced yawning is mediated by the interaction of various brain neurotransmitter systems. Dopaminergic, peptidergic, and cholinergic neurones appear to be primarily responsible for the control of yawning. At the pharmacological level yawning and sexual arousal appears to be useful as a model for identifying drugs with agonist activity at inhibitory dopamine receptors (Gower et al. 1984). Similarly, chewing mouth movements have been proposed as a useful index of agonist action at central muscarinic receptors (Salamone et al. 1986).
In behavioural terms, the evidence suggests that in most cases pharmacologically-induced yawning bears a close resemblance to spontaneous, physiological yawning. Thus, the posture of rats yawning in response to physostigmine or apomorphine is very similar to that of spontaneous physiological yawning in rats (Ushijima et al. 1985). Furthermore, apomorphine induced yawns in rats occur in clusters (Szechtman 1984; Cooper, de Mars, and Dourish, unpublished results) which is consistent with anecdotal reports that yawning in humans occurs; in bures (Barbizet 1958).
The only comprehensive study to date on physiological yawning in animals was carried out by Anias et al. (1984) who produced a "high yawning frequency" line of Sprague-Dawley rats through selective breeding. They found a clear circadian pattern in spontaneous yawning with the highest frequency being evident during the last hour of the light period. Interestingly, this coincides with the time of the lowest daily dopamine turnover rate (Cahill and Ehret 1981) which suggests some form of dopaminergic control of spontaneous yawning.
Spontaneous, physiological yawning is a behaviour categorized by ethologists as a "stereotyped action pattern" (see Provine 1986 and references therein). In humans, yawns can be released by observing yawns, thinking about yawning, or even reading about yawning (Provine 1986). There have been a number of speculations concerning the function of yawning. One proposal is that yawning is useful for "stretching the face". By causing contraction of the facial muscles, yawning forces blood through cerebral vessels to the brain which may have an alerting effect (Heusner 1946; Barbizet 1958). Similarly, it has been suggested that yawning may increase blood oxygen levels during the deep air inspiration which accompanies the response (Bartlett et al. 1971). However, a study by Provine (1986) has cast doubt on the respiratory hypothesis since there was no correlation between yawn duration and interyawn interval (ie. infrequent yawners did not compensate by producing yawns of longer duration).
Yawning is also of clinical interest since it has been reported to be associated with a number of disorders including epilepsy, epidemic encephalitis and Huntington's chorea (Heusner 1946), hysteria and brainstem lesions (Barbizet 1958) and adrenoleucodystrophy (which interestingly is accompanied by high blood ACTH levels; Kataoka et al. 1980). Yawning is also reported to be associated with opiate withdrawal in man (Himmelsbach 1939). In contrast, it has been reported that apomorphine-induced yawning in rats is reduced by the opiate antagonist naloxone (Szechtman 1984). However, it appears that the effects of naloxone on yawning may not be opiate-receptor-mediated (Berendsen and Gower 1986).
It seems likely that yawning may have an important social function both in apes (Hadidian 1980) and in humans (Barbizet 1958). In man, yawning is often regarded as an expression of indifference and/or boredom although social etiquette demands that the yawn is hidden by putting one's hand over one's mouth.
We believe that yawning and stretching may signal the termination of stressful experience or of sustained concentration. Experimental evidence is lacking, but there are anecdotal observations which suggest that yawning and stretching may be behavioural features of recovery from at least certain forms of stress. For example, one of us (SJQ sat amongst a large class of students in Northern Ireland who were being addressed by a visiting rescarch worker. He wanted them to answer direct questions about the impact of the "Troubles'" (ie. the period from 1969 to the present day during which there has been widespread violence) on their personal lives, and on those of their families and friends. The effect of his talk on the behaviour of the students was startling. Under normal circumstances, like students anywhere, his audience would have shown periodic fidgeting, whispering, looking-about, coughing, and so on. On this occasion, however, the entire class sat motionless, and expressionless, when it became clear that they were being asked about widespread fears and anxieties, and about injuries and deaths which may have befalien members of their families, their friends, and neighbours. There was a palpable feeling of tension throughout the lecture room.
As the speaker came to an end of his talk and signalled this by some closing comments, the behaviour of the class changed remarkably. They relaxed their body postures, they turned to classmates and looked at each other, they smiled, and most strikingly, there was a widespread outbreak of yawning and stretching. These changes were closely synchronized throughout the class. It was difficult to discount the impression that the yawning and stretching occurred as part of a more complex change in the students' behaviour, which was initiated by the end of a distressing experience. Formal observations of the behaviour of people, alone or in large groups, during and following the imposition of stress would be extremely interesting. We suggest that the occurrence of yawning and stretching, in people, may form part of a range of behavioural responses indicative of recovery from stressful events. The animal data which we discuss imply that in people, too, yawning and stretching may follow from neurochemical changes in the brain, which include an inhibition of central dopaminergic activity. In rats it is clear that spontaneous yawning; can be significantly altered by environmental manipulation. In animals and man changes in brain dopamine metabolism and yawning frequency may be closely associated with recovery from acute stress.
During the past decade experiments on drug-induced yawning; in animals have facilitated that construction of a model of the neuronal circuity which subserves yawning. Furthermore, yawning in animals has proved to be a useful pharmacological tool for studying neurotransmitter receptors and receptor subtypes. The challenge remains to discover the physiological trigger for yawning and to fully understand the behavioural and social significance of the response.
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-Stoessl AJ Effects of ageing on the behavioural responses to dopamine agonists: decreased yawning and locomotion, but increased stereotypy Brain Research 1989; 495; 20-30
-Stoessl AJ, Dourish CT, Iversen SD The NK-3 tachykinin agonist senktide elicits yawning and chewing mouth movements following subcutaneous administration in the rat. Evidence for cholinergic mediation. Psychopharmacology (Berl). 1988; 95; 4; 502-506
-Cooper SJ; Dourish CT Neural basis of drug induced yawning in neurobiology of stereotyped behaviour Oxford ed 1990
-Cooper SJ, Rusk IN, Barber DJ. Yawning Induced by the Selective Dopamine D2 Agonist N-0437 is Blocked by the Selective Doparnine Autoreceptor Antagonist (+)-UH 232. Physiol Behav. 1989;45:1263-1266
-Dourish CT, SJ Cooper Yawning elicited by sytemic and intrastriatal injection of piribedil and apomorphine in the rat Pyschopharmacology 1985; 86; 175-181
-Dourish CT, PH Hutson Bilateral lesions of the striatum induced with 6-hydroxydopamine abolish apomorphine-induced yawning in rats Neuropharmacology 1985; 24; 11; 1051-1055
-Collins G, JM Witkin et al Dopamine agonist-induced yawning in rats: a dopamine d3 receptor mediated behavior J Pharmacol Exp Ther 2005
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