-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,
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
-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
Introduction : We recently reported
that a stereotyped yawning response can be
evoked by microinjection of L-glutamate, cyanide
and a nitric oxide-releasing compound (NO) into
the medial parvocellular subdivision of the
paraventricular nucleus (PVN) in anesthetized,
spontaneously breathing rats. In those studies,
we recorded the electrocorticogram (ECoG) to
evaluate arousal responses during yawning, and
found that ECoG arousal, represented by lower
voltage and faster rhythms, occurred before the
final yawning behavior during both spontaneous
yawning and yawning responses evoked by chemical
stimulation. This arousal effect was of
considerable significance because the data were
obtained under anesthesia. Although the PVN
is essential for the occurrence of yawning, our
previous studies raised the possibility that the
PVN may play an important role in triggering
arousal mechanisms. We therefore suggested that
the yawning model is appropriate for
investigating arousal mechanisms in
rats.
Orexins (A and B) are a recently identified
family of neuropeptides originally believed to
be important mediators of food intake. Apart
from appetite regulation, orexins have now
emerged as important regulators of sleep and
arousal. For example, Chernelli
et al. proposed that orexin knockout mice
may be a model for human narcolepsy. They
further observed that orexin neurons innervate
neurons critical for controlling arousal in
the ascending cortical activation system.
Hagan et
al. demonstrated that orexin-A activates
locus coeruleus cell firing in vitro and
increases arousal in rats in vivo. Moreover,
Piper et al. reported that orexin-A modifies the
sleep wake cycle of rats. In those studies,
orexin-A stimulated arousal after
intracerebroventricular injection, but the
precise site of action within the brain for
orexin-A to stimulate arousal remains unknown.
We sought to determine whether the PVN is orexin
sensitive by microinjecting orexin-A into the
specific region within the PVN where a
stereotyped yawning response was induced by
L-glutamate. The effect of orexin-B
microinjection into the PVN was also examined.
The doses of orexin-A and orexin-B used in the
present study were at least 1000 times smaller
than those used for feeding responses in
microinjection studies of the PVN. All
microinjections were done with multi-barrel
glass micropipettes which provide especially
high resolution, thus stimulating only a
restricted region within the PVN.
[....] The yawning response has
important physiological significance for arousal
in anesthetized animals. It is apparent from
observing human subjects that yawning is not a
behavior restricted to mouth opening, but is a
coordinated motor pattern characterized by a
deep inspiration and stretching of the trunk.
Yawning is also accompanied by changes in
autonomic function, including a depressor
response, lacrimation and erection. Furthermore,
yawning is a phenomenon that subserves
arousal.
To evaluate these various physiological
aspects of yawning, we monitored polygraphic
measures representing a yawning response in
anesthetized, spontaneously breathing rats. It
is important to emphasize that if we used
conscious animals, the data obtained would be
almost certainly restricted to counting the
number of mouth openings, which shows only one
aspect of the entire yawning response. Whereas
the ECoG of anesthetized rats is normally
characterized by high voltage and very slow
waves (2Hz), faster rhythms (4Ð6 Hz) became
dominant afterchemical stimulation of the
PVN.
Since this arousal shift in the ECoG was
usually accompanied by yawning responses, we
suggest that the PVN mediates the cortical
activation related to yawning. In this
respect, Dringenberg and Vanderwolf demonstrated
that several pathways contribute to ECoG
activation as well as arousal mechanisms. Our
findings indicate that the PVN plays a
significant role in the arousal mechanism
related to yawning. Narcolepsy, a disorder
characterized by excessive daytime sleepiness,
cataplexy, and striking transitions from
wakefulness into rapid eye movement sleep, is
apparently caused by orexin and orexin receptor
deficiency in human and animal models. The type
of orexin receptor deficiency in this disorder
is OX2R, which is predominantly found in the
PVN. These data together suggest orexin as a
major neurotransmitter involved in sleep and
arousal mechanisms, and further strengthen our
hypothesis that the PVN plays an important
role in arousal systems.
In conclusion, microinjection of orexin-A
into the PVN elicited an arousal/yawning
response, whereas orexin-B injection induced
the arousal response alone. The results
demonstrate that an orexin receptive site for
triggering arousal/yawning responses exists in
the PVN. Our finding should open a new avenue of
research to investigate the role of the PVN in
arousal regulation.
-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. Lettre
2008;
-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,
Sato-Suzuki et al.Yawning responses induced
by local hypoxia in the paraventricular nucleus
of the rat.Beh Brain Res 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
-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.
-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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LL; De Medeiros R; Neumann B; Tufik S
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