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Première conférence internationale sur le bâillement
First International Conference on Yawning
Paris 24 - 25 juin 2010
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 gregory collins
The Neurophamacology of Yawning
Gregory T. Collins
Department of Pharmacology University of Michigan Medical School Ann Arbor USA
Jose R. Eguibar
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México
Yawning is a common behavioral event that is observed in humans, as well as other mammals, birds, and reptiles. In humans, yawning often occurs just before bed and upon waking up, and is also associated with tedious or boring situations. Although the physiologic roles of yawning have yet to be fully elucidated, the past 50 years of research has led to a much greater understanding of the neuropharmacologic regulation of yawning. While many of the early studies concluded that yawning was primarily driven by changes in cholinergic neurotransmission, we now know that numerous neurotransmitters and neurohormones are involved in the mediation of yawning, including acetylcholine, dopamine, glutamate, serotonin, oxytocin, GABA, opioids, adrenergics, nitric oxide, as well as the POMC-derived peptides ACTH and a-MSH. Furthermore, antagonist interaction studies have clearly defined at least three distinct neural pathways involved in the induction of yawning, as well as the hierarchical order through which these different neurotransmitter systems interact to regulate yawning. The following sections will discuss the state of knowledge for each of the major neurotransmitters and neurohormones involved in the regulation of yawning, their interactions with one another, and their place in the hierarchical organization of yawning.
Pharmacological and environmental regulation on yawning in the high-yawning (HY) subline of Sprague&endash;Dawley rats.
Jose R. Eguibar, Cortés Ma del Carmen and Uribe Carlos
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México
The high-yawning (HY) subline was obtained at the Institute of Physiology in the Benemérita Autonomous University of Puebla through a strict inbreeding process along 75 generations. This group of rats showed a spontaneous yawning frequency more than 20 times/h. On the other hand, low-yawning (LY) rats have a mean yawning frequency around 2 times/h, and were selected from another stock of Sprague-Dawley by inbreeding process through 60 generations.
The availability of HY rats allows us to analyze the environmental influences that regulated yawning expression. So, we demonstrated that yawning showed a circadian oscillation with a clear peak before darkness. This circadian rhythm did not show a free running under constant light conditions, but it is possible to synchronize it whit a restricted availability of food or water, which produced a clear peak of yawning that predicts their presentation.
On the other hand, HY rats are more sensible to presynaptic dopaminergic D2/D3 agonist such as: apomorphine, 3-PPP, quinpirole or 7-OH-DPAT. Central administration of adrenocorticotropin hormone (ACTH1-24) no clear effect were obtained on yawning frequency in the HY subline, probably due to displacement produced by the increase in frequency and duration of grooming bouts. On the other hand, central administration of bombesin, a gastrointestinal peptide, inhibits yawning in HY rats. Also is the case with GABAa and GABAb agonists which inhibits spontaneous and cholinergic-induced yawning. In the case of cholinergic agonists such as physostigmine or pilocarpine produced larger increase on yawning frequency in HY respect to LY rats.
HY rats showed different responses in the elevated plus maze and burying test. In fact, HY subline showed lower corticosterone level after immobilization in a cylinder respect to LY ones. These results clearly indicate that stress induced different responses in hypothalamus-pituitary-adrenal glands in both sublines.
In conclusion, HY subline allows us to analyze with detail pharmacological and environmental factors that modulate yawning frequency. It is clear that the behavioural and environmental differences in HY rats are due to differences in the biochemical pathways involved in synthesis, release or metabolism of neurotransmitters and modulators involved in the regulation of yawning.
This work is partly supported by VIEP-BUAP SAL/G/2009 and CONACYT 106,694 grants to JRE and by Dr. E. Agüera-Ibañez, Rector-BUAP.

Dopamine Agonist-Induced Yawning in Rats: A Dopamine D3 Receptor Mediated Behavior
A specific role for the dopamine D3 receptor in behavior has yet to be elucidated. We now report that dopamine D2/D3 agonists elicit dose-dependent yawning behavior in rats, resulting in an inverted U-shaped dose-response curve. A series of experiments was directed toward the hypothesis that the induction of yawning is a D3 receptor mediated effect, while the inhibition of the yawning observed at higher doses is due to competing D2 receptor activity.

Although its physiological function is still poorly understood, yawning is under the control of several neurotransmitters and neuropetides at the central level as this overview of litterature on neurochemistry of yawning show. Among these substances, the best known are dopamine, excitatory aminoacids, acetylcholine, serotonin, nitric oxyde, adrenocorticotropic hormone-related petides and oxytocin, that falicitate yawning and opiod peptides that inhibit this behavioral reponse. Some of the above compounds interact in the paraventricular nucleus of the hypothalamus to control yawning. This hypothalamic nucleus contains the cell bodies of oxytocinergic neurons projecting to extra-hyopthalamic brain areas that play a key role in the expression of this behavioral event.