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mise à jour du 30 janvier 2003
Physiology & Behavior 1995;57(5):967-971
Apomorphine induced yawning in the rat : influence of fasting and time of day
Naselo A, Tieppo C, Felicio L
Medical School of Santa Casa, Sao Paulo, Brazil
Circadian variation of yawning behavior Anias J et al


Yawning, suppression of exploration, and penile erection are behavioral patterns that occur concomitantly under some conditions. These behaviors are elicited by low doses of the dopamine (DA) receptor agonist apomorphine (APO). It also has been proposed that they may be useful as a behavioral model for negative symptoms of schizophrenia. These three behavioral parameters are also elicited by low doses of other DA agonists. The clinical usefulness of APO as well as other DA agonists on schizophrenia and hyperkinetic disorders has also been reported. Yawning alone or associated with stretching is considered as an ancestral vestige, surviving throughout the evolution, that subserves the purposes of arousal.

It has been suggested that dopaminergic mechanisms controlling yawning are central because domperidone, a DA antagonist that does not cross the blood-brain barrier, has no effect on this behavior. There are several reports about the central nucleus and circuits involved in yawing expression. There are also many studies showing how this behavior is influenced by drugs such as pilocarpine, physostigmine, scopolamine, haloperidol, sulpiride, remoxipride, rnetoclopramide, morphine, buspirone and others, as well as by hormones like ACTH, oxytocin, LHRH, and a-MSH. In addition, it is modified by REM sleep deprivation. However, very little is known about the influence of feeding and time of day on the modulation of this behavior.

To further our knowledge conceming the influence of these physiological variables, this study was designed to assess the influence of 24- and 48-h fasting and light-dark cycle on the expression of APO-induced yawning. [...]

Gamberini MT, Bolognesi ML, Nasello AG. The modulatory role of M2 muscarinic receptor on apomorphine-induced yawning and genital grooming. Neuroscience Letters 2012; 531:91-95

-Gamberini MT, Gamberini MC, Nasello AG. Involvement of dopaminergic and cholinergic pathways in the induction of yawning and genital grooming by the aqueous extract of Saccharum officinarum L. (sugarcane) in rats. Neuroscience Letters 2015;584:270-275
-Naselo A, Tieppo C, Felicio L Apomorphine induced yawning in the rat : influence of fasting and time of day Physiology & Behavior 1995;57(5):967-971
-Nasello AG et al Modulation by sudden darkness of apomorphine-induced behavioral responses Physiology & Behavior 2003;78:521-525
Discussion :

The importance of studying yawning behavior is clear from the point of view of physiological responses or as an experimental tool to elucidate the mechanisms of actions of drugs and hormones. In addition, this behavior serves as a paradigm for some diseases and for clinical applications of low doses of dopamine agonists.

Our results show that: 1) 100 µg/kg is a more effective dose than 50 or 150 Mg/kg APO; 2) 24-h or 48-h fasting significantly reduce APO-induced yawning-, 3) during the dark period APOinduced yawning is significantly more intense than during the light period.

APO doses ranging from 30 to 250 µg/kg are reported as being able to elicit yawning behavior. The purpose of our first experiment was to determine the most appropriate dose of APO to induce yawning in rats in our laboratory conditions. Dose-response and time-response curves were built; 100 µg/kg was the most effective dose. The doses of 50 and 150 µg induced lower responses: the results obtained with the lowest dose may be because 50 µg/kg is under the dose necessary for a maximal response whereas 150 µg/kg APO was too high and induced stereotypy, which is a behavior that excludes yawning. The maximal response occurred in the 10-20min interval for the doses of 50 and 100 µg/kg and in the 2030-min interval for 150 µg/kg. Because the highest dose elicited stereotyped behavior, it may be necessary to wait for the drug to be metabolized for the optimum yawninginducing dose to be achieved. Thus, we chose 100 µg/kg APO for the following experiments.

Distinct areas of the brain are modified differently by fasting. Fasting drastically diminished the response to APO: 24-h food deprivation is enough to modify this behavior. The 48-h food-deprivation effects on yawning were not different from the 24-h fasting effects. Yawning decrease seems to bc maximal at 24-h of food deprivation. One-hour feeding before the test does not reverse this reduction, suggesting that this behavioral change is persistent and not rapidly reversed by a meal. On the other hand, we have previously demonstrated that fasting followed by previous meal modifies the expression of 100 µg/kg APO-induced behaviors such as genital grooming and pende erection . The present results show that a previous meal reduces yawning more intensely in 48-h than in 24-h food-deprived rats. Ibis finding suggests that, in some physiological states, a meal can inhibit yawning.

The dark period is the time for physiological arousal for rats; during this period there is an increase in some behaviors, such as motor activity and sexual behavior. We observed that during the dark period the yawning response to APO, a dopamine agonist, was significantly higher than during the light period. Ilis result suggests that dopaminergic responses are increased during the dark period. This increase in APO-induced yawning may be due to a decrease in the activity of dopamine neurons or tu an increase in the dopamine receptors' sensitivity, or both. Fasting increases the DA turnover in the hippocampus but not in the hypothalamus, striatum, and cortex. Yawning is not telated te, extracellular striatal levels of DA. It can be speculated that the DA receptors' sensitivity may be modified during fasting and the dark peried.

The role that each of the DA receptor subtype activation plays on these behaviors is not well established. Dopamine D2 autoreceptor used to be considered as being the only DA teceptor involved in yawning and pende erection syndrome; other authors considered the involvement of D, receptors (9,19,42) or a simultaneous activation of Dl and D2 receptors. More recently, accumulating evidence suggests that a special subpopulation of D2 postsynaptic receptors, possibly D3 subclass, may play a relevant role in these dopaminergic behaviors.

The sensitivity of some DA receptors is also modified by a large number of manipulations [e.g., the response to APO is modified in the deprivation of long-term treatment with bromopride, a D2 antagonist]; this response is also modified in offspring of dams treated with bromopride (l 1) or quinpirole (20) during pregnancy and/or lactation. Changes in APO tesponse might also depend on mechanisms beyond or independent of DA receptors [e.g., acetylcholine, oxcytocin, ACTH, LHRH, nitric oxide, and a-MSH.

Our results suggest that fasting and time of day may modify the DA receptors' sensitivity in the brain areas involved with yawning. This finding has many practical consequences, because it has been reported that low doses of DA agonists are effective in various psychiatric conditions like schizophrenia and Gille dela Tourette's disease, as well as neurological disorders such as Huntington chorea, tardive dyskinesia, and torticollis. Further study are necessary to verify how 24-h fasting and the dark period differentially modify the activity od dopaminergic systems.