Emotional
stress evoked by classical fear
conditioning
induces
yawning behavior in rats
Kubota N, Amemiya S, Yanagita S, Nishijima
T, Kita I.
Department of Human Health
Science, Tokyo Metropolitan University
Japan
Abstract
Yawning is often observed not only in a
state of boredom or drowsiness but also in
stressful emotional situations, suggesting that
yawning is an emotional behavior. However, the
neural mechanisms for yawning during stressful
emotional situations have not been fully
determined, though previous studies have
suggested that both parvocellular oxytocin (OT)
and corticotropin-releasing factor (CRF) neurons
in the hypothalamic paraventricular nucleus
(PVN) are responsible for induction of
yawning.
Thus, using ethological observations and
c-Fos immunohistochemistry, we examined whether
emotional stress evoked by classical fear
conditioning is involved in induction of yawning
behavior in freely moving rats. Emotional stress
induced yawning behavior that was accompanied by
anxiety-related behavior, and caused neuronal
activation of the central nucleus of the
amygdala (CeA), as well as increases in activity
of both OT and CRF neurons in the PVN. These
results suggest that emotional stress may induce
yawning behavior, in which the neuronal
activation of the CeA may have a key role.
-Kita I, Kubota N,
Yanagita S, Motoki C Intracerebroventricular
administration of corticotropin-releasing factor
antagonist attenuates arousal response
accompanied by yawning behavior in rats.
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oxytocinergic neurons in the paraventricular
nucleus in oxytocin-induced yawning and penile
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Sato-Suzuki et al.Yawning responses induced
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S, Motoki C, Otsuka T, Nishijima T, Kita I.
Corticotropin-releasing factor antagonist
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N, Amemiya S, Yanagita S, Kita I. Neural
pathways from the central nucleus of the
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hypothalamus are involved in induction of
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Yawning is often observed not only in a
state of boredom ordrowsiness, but also in
stressful emotional situations in humans and
other animals. Ethological and psychological
studies in primates have reported yawning
following neighboring individualsthat are
vocalizing and showing sexual jealousy
[4,5]. Clinical reports have shown that
yawning is frequently observed in anxiety
disorders, including patients with hysteria,
depression, and motion sickness [7,28].
In addition, Major et al. [19] reported
that anxiogenic compounds induce anxiety-like
behavior in monkeys that is accompanied by
yawning. Thus, yawning is considered an
emotional behavior.
Previous pharmacological and lesion studies
have suggested that the paraventricular nucleus
of the hypothalamus (PVN) is essential for the
occurrence of yawning [3,26].
Additionally, we have reported that both
parvocellular oxytocin (OT) neurons and
corticotropin-releasing factor (CRF) neurons in
the PVN, each of which sends descending axons to
the lower brainstem involved in either arousal,
respiratory, cardiovascular, or other autonomic
functions, are responsible for yawning that is
accompanied by an arousal response
[14&endash;16].
Although these results suggest that the
stereotyped yawning response is mediated by both
parvocellular OT and CRF neurons in the PVN, the
mechanisms of yawning during stressful emotional
situations have not been fully determined.
The amygdala is generally known to play a
pivotal role in emotion [1,2]. The
central nucleus of the amygdala (CeA), which is
a part of the amygdaloid complex, is
particularly known to be essential for
integration of behavioral, autonomic, and
hormonal responses to emotional stress, and is
one of the most important output regions an
intrinsic reward, known as the "warm glow"
effect. Humans report feeling good when they do
good and show activation of reward-related brain
for the expression of these emotional responses
[18,20]. In addition,neuroanatomical and
functional studies have suggested the importance
of connections from the CeA to the PVN for
stress responses[10,12,13]. Thus,
yawning during emotional stress may be induced
through activation of CeA neurons, as well as
both parvocellular OT and CRF neurons in the
PVN. In the present study, using ethological
observation and c-Fos immunohistochemistry in
rats, we investigated whether emotional stress
is involved in induction of yawning
behavior.
4. Discussion
To the best of our knowledge, this is the
first study to determine the involvement of
emotional stress in induction of yawning
behavior using ethological observations and
c-Fos immunohistochemistry in rats. Classical
fear conditioning induced yawning behavior
accompanied by anxiety-related behavior, and
caused neuronal activation of the CeA, as well
as increases in activity of both OT and CRF
neurons in the PVN. These results suggest that
emotional stress may induce yawning
behavior.
The present study showed that yawning
behavior was observed after fear conditioning,
which is a common model to produce anxiety
[11,20]. Our results showed significant
decreases in the number of entries into the
center of the field, lines crossed, and rearing
after fear conditioning, suggesting that the
fear conditioning used in the present study
produced anxiety. Previous studies in monkeys
have shown that anxiogenic compounds induce
anxiety-like behavior that is accompanied by
yawning [17,19], and that yawning is
observed in stressful emotional situations, such
as in punishment-induced fear and neighboring
individuals who are vocalizing and showing
sexual jealousy [4,5,22]. Thus, yawning
behavior may be a type of emotional behavior
caused by emotional stress.
The neural mechanisms underlying yawning as
a type of emotional behavior are poorly
understood. The PVN plays a critical role in
behavioral and arousal responses that are
associated with various stressors [9,21]
and is the most important brain structures for
the induction of yawning behavior
[3,26]. We have reported that both
parvocellular OT and CRF neurons in the PVN are
responsible for the yawning that is accompanied
by arousal responses [14&endash;16].The
present study showed increases in activity of
both parvocellular OT and CRF neurons in the PVN
during emotional stress, suggesting that
emotional stress may induce yawning behavior
directly or indirectly through neuronal
activation of the PVN which is responsiblefor
induction of yawning.
What type of signaling pathway is involved
in the emotionalstress-induced yawning behavior
that is mediated by the PVN? Neuroanatomical and
functional studies have suggested that
connections from the CeA to the PVN may be
important for stressand emotional responses
[10,12,13]. Gray et al. [12]
reported thatinjections of an anterograde tracer
into the CeA resulted in a few labeled axons and
terminals within the caudal lateral and medial
parvocellular regions of the PVN, indicating
that the CeA directly innervates the PVN
[6,13]. On the other hand, the CeA is
wellknown to send dense projections to the bed
nucleus of the stria terminalis [8,13],
which is one of the brain regions that is
involved in emotional responses and that densely
innervates the PVN. Furthermore, several studies
have shown that emotional and physical stress
increases neuronal activation of the portions of
the amygdala that project to the PVN and induces
behavioral and physiological responses, whereas
lesions of the CeA block or greatly attenuate
stress responses [10,12,13]. Recently,
pharmacological study suggested the involvement
of mesolimbic regions including amygdala in
induction of yawning [25]. Taken
together, it is possible that neuronal
activation of the CeA caused by emotional stress
may beinvolved in the induction of yawning as an
emotional behavior.
Unfortunately, our data provide a
correlation between neuronal activation in the
CeA and yawning, but there is no real evidence
in this study that they are related. This
possibility should be investigated further using
physiological, anatomical, and lesion
studies.
In summary, we observed yawning behavior
that was accompanied by anxiety-related behavior
during emotional stress in which a state of
anxiety was evoked by classical fear
conditioning. The emotional stress increased
neuronal activation of the CeA, as well as
increases in activity of both OT and CRF neurons
in the PVN which are responsible for induction
of yawning. These results suggest that emotional
stress may induce yawning behavior, in which the
neuronal activation of the CeA may have a key
role.
