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Leptine, ghréline, histamine et bâillements

 

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mise à jour du
15 septembre 2002
Behavioural Brain Research 2002;134:75-82
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Yawning/cortical activation induced by microinjection of histamine into the paraventricular nucleus of the rat
 
Yoshinari Seki, Ikuko Sato-Suzuki, Ichiro Kita,
Mitsugu Oguri, Hideho Arita
Department of Physiology, Toho University School of Medicine, Ohta-ku, Tokyo Japan

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-Kita I, Kubota N, Yanagita S, Motoki C Intracerebroventricular administration of corticotropin-releasing factor antagonist attenuates arousal response accompanied by yawning behavior in rats. Neurosci.Letter 2008;433(3):205-208 
-Kita I, Yoshida Y, Nishino S. An activation of parvocellular oxytocinergic neurons in the paraventricular nucleus in oxytocin-induced yawning and penile erection. Neurosci Res. 2006;54(4):269-275
-Kita I, Seki Y, Nakatani Y, Fumoto M, Oguri M, Sato-Suzuki I, Arita H. Corticotropin-releasing factor neurons in the hypothalamic paraventricular nucleus are involved in arousal/yawning response of rats. Behav Brain Res. 2006;169(1)48-56.
-Kita I, Sato-Suzuki et al.Yawning responses induced by local hypoxia in the paraventricular nucleus of the rat.Behavioural Brain Research 2000;117(1-2):119-126
-Kubota N, Amemiya S, Motoki C, Otsuka T, Nishijima T, Kita I. Corticotropin-releasing factor antagonist reduces activation of noradrenalin and serotonin neurons in the locus coeruleus and dorsal raphe in the arousal response accompanied by yawning behavior in rats. Neurosci Res. 2012;72(4):316-323
-Kubota N, Amemiya S, Yanagita S, Nishijima T, Kita I. Emotional stress evoked by classical fear conditioning induces yawning behavior in rats. Neurosci Lett. 2014 Mar 11.
-Seki Y, Y Nakatani, et al Light induces cortical activation and yawning in rat Behav Brain Res 2003;140(1-2):65-73
-Seki Y, Sato-Suzuki I, et al Yawning/cortical activation induced by microinjection of histamine into the paraventricular nucleus of the rat. Behav Brain Res. 2002;134(1-2):75-82.
-Sato-Suzuki I, Kita I, Oguri M, Arita H Stereotyped yawning responses induced by electrical and chemical stimulation of paraventricular nucleus of the rat Journal of Neurophysiology, 1998;80(5)2765-2775
-Sato-Suzuki I, I Kita, Seki Y, M Oguri, H Arita Cortical arousal induced by microinjection of orexins into the paraventricular nucleus of the rat Behavioural Brain Research 2002;128:169-177

Introduction : We have reported that a stereotyped yawning response can be evoked by several chemical stimulations of the paraventricular nucleus (PVN) in anesthetized, spontaneously breathing rats. A typical yawning response is induced by microinjection of L-glutamate in the medial parvocellular subdivision (mp) of the PVN, and is characterized by an initial depressor response and an arousal shift in electrocorticogram (ECoG) followed by a single large inspiration with mouth opening. Our concept that the PVN is essential for the occurrence of yawning is compatible with previous data of Argiolas and Melis who demonstrated that lesions of the PVN prevents yawning induced by apomorphine and oxytocin in freely moving rats. On the other hand, two physiological roles of the PVN concerning yawning have been newly suggested by our recent findings:
 
-1- An oxygen sensor may exist within the PVN and yawning may be an arousal behavior caused by higher brain ischemia, since microinjection of cyanide into the mp caused the stereotyped yawning response.
 
-2- The PVN may play an important role in triggering arousal mechanisms, since microinjection of orexin-A, a neuropeptide involved in sleep and arousal mechanisms, into the mp caused thestereotyped yawning response.
 
Yawning is one typical symptom of motion sickness. The involvement of histamine in neural processes of motion sickness is suggested by several pieces of evidence. In animal models of motion sickness, the histamine level in the hypothalamus increases after rotation. Another piece of evidence comes from Takeda observation that administration of fluoromethylhistidine, an inhibitor of histamine synthesizing enzyme, suppresses the signal of motion sickness in rats. It is also clinically well known that antihistaminics are effective in preventing motion sickness in humans. These data on motion sickness led us to speculate that the yawning behavior might also be affected by histaminergic neural transmission.
 
The neurons responsible for yawning are proved to be the oxytocinergic parvocellular neurons in the PVN projecting to the lower brain stem. On the other hand, oxytocinergic parvocellular neurons in the PVN are reported to be activated by histamine. These two data together support our idea that yawning might be affected by histamine. The present study focused on the yawning response induced by microinjection of histamine into the PVN. Attempts were further made to identify whether the H1 receptor in the PVN mediates this response. [...]
 
Discussion : We found that the stereotyped yawning response was activated by local application of histamine into the PVN, which indicates that the PVN is a region receiving histaminergic inputs from the tuberomammillary nucleus (TM) of the posterior hypothalamus, a region where histaminergic neurons are densely located. Our view that the PVN is a histamine sensitive site is supported by three pieces of evidence.
 
-1- Panula demonstrated that histaminergic neurons originating in the TM project to other brain areas including the PVN. Another piece of evidence comes from an autoradiographic study showing the presence of histamine receptor in the PVN. Finally, Bealer and Abell caused effective cardiovascular responses by applying histamine through microdialysis probes into the PVN. Our data showing that histamine administered into the PVN induced yawning, together with an arousal shift in the ECoG, confirms the results of previous studies which showed that histamine is an important neurotransmitter in arousal regulation. Experimental lesioning of the posterior hypothalamus has been reported to induce a state of somnolence in rats . In addition, the decrease in histamine content of the brain suppresses wakefulness in rats. Conversely, histaminergic drugs cause wakefulness in rats. These arousal effects of histaminergic systems are thought to be mediated by H1 receptors. It is also clinically well known that antihistaminics induce drowsiness. Moreover, particularly high levels of histamine receptors are present in area involved in arousal, i.e. the cerebral cortex, cholinergic cell groups in the mesopontine tegmentum (MPT) and in the basal forebrain, as well as the locus coeruleus (LC).
 
-2- We further indicate that not only histamine but also PVN is involved in the arousal signaling pathway, since microinjection of histamine into the PVN induced the arousal shift in the ECoG together with the yawning response. It should be emphasized that no other area in or around the PVN elicited the arousal/yawning response. These data may strengthen the hypothesis proposed in our previous study, that the PVN is a site involved in the arousal mechanism. According to the arousal pathway referred to as histaminergic transmission, several possible pathways are nominated. Arousal may be due to histaminergic neurons originating in the TM directly projecting to the cerebral cortex. On the other hand, it may be due to histaminergic neurons projecting to the cholinergic cell groups in the MPT or in the basal forebrain as well as the LC. Here we suggest another signaling pathway of the arousal mechanism via the PVN. Namely, histaminergic neurons from the TM may directly activate parvocellular neurons in the PVN, which in turn project to the basal forebrain or the LC. We previously reported that the neurons responsible for yawning might be the oxytocinergic parvocellular neurons in the PVN projecting to the lower brainstem. Our suggestion was mainly based on the report of Sawchenko and Swanson who demonstrated that oxytocinergic parvocellular neurons in the PVN send descending axons to the lower brain stem which region is involved in arousal, respiratory, cardiovascular, and other autonomic functions. According to this notion, the present data can be explained by the possibility that histamine activates the oxytocinergic parvocellular neurons in the PVN projecting to the lower brain stem. This possibility is strongly supported by the data of Kjær who reported that c-fos expression in oxytocinergic parvocellular neurons within the PVN is induced by central administration of histamine. They further suggested that histamine might be indirectly involved in the regulation of neurons in the lower brain stem and the spinal cord via the PVN.
 
-3- Although we suggest that the oxytocinergic parvocellular neurons in the PVN are involved in yawning, we can not exclude the possibility that the PVN may contain more than one pathway mediating this response. For instance, ACTH injected into the PVN and surrounding periventricular region induces yawning that is not prevented by oxytocin antagonist. Corticotropin releasing factor (CRF) neurons within the PVN could be responsible for the ACTH-induced yawning, however, there is little evidence that CRF neurons project to the lower brain stem which region is involved in arousal, respiratory, cardiovascular, and other autonomic functions regarded to yawning.
 
We indicate that histamine activates the H1 receptor in the PVN, since the yawning response induced by histamine was inhibited by pretreatment with pyrilamine, an H1 receptor antagonist. Moreover, microinjection of HTMT dimaleate, an H1 receptor agonist, into the PVN, evoked the yawning response. Similarly to our data, Gower reported that H1 receptor antagonist injected subcutaneously into conscious rats inhibited the apomorphine-induced yawning response. With regard to this view, an autoradiographic study revealed the presence of H1 receptor in the PVN. The existence of H1 receptor in the PVN has also been examined in functional studies.
 
For example, Bealer demonstrated that histamine evokes norepinephrine as well as oxytocin release by activation of H1 receptors in the PVN. H1 receptors in the PVN are also reported to be involved in histaminergic suppression of food intake. Although H1 receptor may be important in the modification of the yawning/arousal response, the role of other types of histamine receptors cannot be fully eliminated. In this connection, Ferrari and Baggio reported that H2 receptor antagonist dose-dependently antagonized the yawning and penile erection induced by apomorphine.
 
In line with their data, yawning response was sometimes induced by H2 receptor agonist into the PVN in the present study. However, H2 receptor agonist induced a yawning response with a much longer onset latency compared with that of histamine or H1 agonist. In addition, pretreatment with H2 receptor antagonist did not block the yawning response induced by histamine in our study. Further study is required before the precise mechanism of histamine actions on yawning/arousal responses can be identified.
 
We noticed that a pressor response appeared after the yawning behavior induced by microinjection of histamine into the PVN, which lasted over 90 s. In this connection, Bealer and Abell demonstrated that administration of histamine through microdialysis probes in the PVN increased BP in conscious rats. It is suggested that the PVN is a brain site where histaminergic and noradrenergic systems interact to regulate BP, and the pressor response evoked by histamine may be due to adrenoreceptor stimulation of vasopressin release. Although the increase in HR was prominent after injection of H2 agonist into the PVN (data not shown), we could not observe a clear increase in HR by histamine injection into the PVN, which result differs from that in conscious animals. The lack of changes in HR by histamine in this study might be attributed to the possibility of anesthetics used, since anesthesia is well known to affect the cardiovascular and autonomic responses.
 
Since yawning is one typical symptom of motion sickness a disorder which is modified by histaminergic transmission, the present results can be explained by the notion that yawning is triggered by motion sickness which signaling pathway is mediated by histaminergic neurons. According to our data showing that yawning was inhibited by H1 receptor antagonist, together with previous data showing that motion sickness is suppressed by H1 antagonist, it is likely that histamine induces yawning as well as motion sickness through H1 receptor within the PVN.
yawing-arousal
-Kita I, Yoshida Y, Nishino S. An activation of parvocellular oxytocinergic neurons in the paraventricular nucleus in oxytocin-induced yawning and penile erection. Neurosci Res. 2006
-Kita I, Seki Y, Nakatani Y, Fumoto M, Oguri M, Sato-Suzuki I, Arita H. Corticotropin-releasing factor neurons in the hypothalamic paraventricular nucleus are involved in arousal/yawning response of rats. Behav Brain Res. 2006; 169; 1; 48-56.
-Kita I, Sato-Suzuki et al.Yawning responses induced by local hypoxia in the paraventricular nucleus of the rat.Behavioural Brain Research 2000; 117; 1-2; 119 - 126
-Sato-Suzuki I, Kita I; Oguri M, Arita H Stereotyped yawning responses induced by electrical and chemical stimulation of paraventricular nucleus of the rat Journal of Neurophysiology, 1998; 80, 5; 2765-2775
-Sato-Suzuki I, I Kita, YSeki, M Oguri, H Arita Cortical arousal induced by microinjection of orexins into the paraventricular nucleus of the rat Behavioural Brain Research 2002; 128; 169-177
-Seki Y, Y Nakatani, et al Light induces cortical activation and yawning in rat Behav Brain Res 2003; 140; 1-2; 65-73
-Seki Y, Sato-Suzuki I, et al Yawning/cortical activation induced by microinjection of histamine into the paraventricular nucleus of the rat. Behav Brain Res. 2002;134(1-2):75-82.