Depto. de Neurociencias,
Instituto de Fisioloġa Celular,
Mexico
Introduction Yawning is a
phylogenetic behavior observed in mammals,
birds, and possibly reptiles. Although it
has
been studied from Hypocrates, the first
experimental report was published in
1963 by Ferrari et al.
The physiological function of yawning
behavior is still unknown. Ferrari's studies
showed that adrenocorticotropine hormone (ACTH),
a-melanocyte-stimulating hormone (a-MSH) and
related peptides induce the stretching-yawning
syndrome, when injected directly into the
cerebral ventricles or third ventricle, but not
by peripheral injection. Since then, several
reports have attempted to elucidate the
mechanism of yawning behavior.
Thus, other hormones like oxytocin and
testosterone, neurotransmitters such as dopamine
and nitric oxide, ions and brain structureshave
been described as being involved in this
behavior. In addition, some researches have
shown
that the hypothalamicÐadrenal axis (HPA)
may also be involved. The hypothalamus has been
identified as one ofthe brain sites for the
action of ACTH and a-MSH's on stretching-yawning
syndrome. Stress effects on yawning behavior has
also been studied. Stressful manipulations
modify yawning's induction by drugs and yawning
trace adjustment to unfamiliar environments in
the laboratory. To date, there is only one study
showing an effect of dexamethasone on yawning
behavior, but there are no studies on the role
of adrenal glands. The aim of the present study
was, therefore, to investigate the effects of
adrenalectomy (ADX) and dexamethasone (DEX)
replacement on yawning behavior.
[...]
Discussion Our results show for the
first time that ADX practically abolished
spontaneous and APO-induced yawning. This effect
although reverted by DEX, was shown not only to
be variable in time, but was also dose
dependent. The yawning suppression produced by
ADX in our study could be understood from two
different, but closely related points of view:
first, the fall of blood corticosterone levels
that is well known to occur following ADX. ADX
can change function, structure, or the receptor
levels of glucocorticoids which alter normal
functioning.
The
paraventricular nucleus could change their
activity by glucocorticoid reduction. This
nucleus is also an important structure involved
in yawning behavior. The reduction of
corticosterone levels as a main cause for
yawning suppression is supported by the fact
that DEX replacement restored yawning behavior.
ADX produces a vertical downward shift of
amphetamine and cocaine locomotor responses,
which is reversed in a dose-dependent manner by
corticosterone administration.
Further evidence comes from the fact that
adrenalectomy reduces the locomotor response
induced by injection of psychostimulant drugs
into the nucleus accumbens, which is then
re-established by restoring basal levels of
corticosterone. In addition, adrenalectomy
decreases extracellular concentration of
dopamine in the nucleus accumbens, both in basal
conditions and in response to psychostimulant
drugs and these effects are reverted by
corticosterone replacement. Moreover, dopamine
administration into the nucleus accumbens
elicits yawning behavior. Debora et al. showed
that single or repeated dexamethasone does not
modify apomorphine-induced yawning.
The discrepancy of these results with that
shown in the present study could be explained by
the dose used. We observed similar results at
the lower concentration used (1 mg/kg). The
relation of ADX effects through changes of PVN
nucleus activity is supported by the fact that
PVN lesions prevents yawning induced by oxytocin
and APO, but not by ACTH administered
intracerebrally. It is thus conceivable that a
PVN functional change provoked by ADX is
strongly involved in the suppression of
spontaneous and APO-induced yawning. The
different effects observed after a single
injection of DEX through 28 h in sham animals,
could be produced by the different stressors
elicited, which induce different responses on
yawning frequency. Some reports showing that 24
h REM sleep deprivation suppresses ACTH-induced
yawning, whereas 96 h of REM deprivation
abolished APO and cholinergic agonist-induced
yawning, effects lasting even afterafter a 24-h
recovery period.
Furthermore, weak and intermittent stress,
such as foot shock and forced swimming, provokes
increased yawning with similar drugs. Such
controversial results are in agreement with some
reports which have shown that the increase of
ACTH and corticosterone in plasma are different
depending on the nature of the stress. Thus, we
could propose that the suppressive effects on YF
observed in our study immediately after
injection, of a supraphysiological dose of DEX
could be compared to the effect of strong and
constant stress, while the increase of YF
occurring at 3 h (5 mg/kg), 5 h (10 mg/kg), and
24 h (20 mg/kg) could be caused by the vanishing
effects of DEX and similar to the effects of
weak and/or intermittent stress. The effect of 1
mg/kg of DEX falls within this latter category.
The latter is supported by the fact that one low
dose of DEX (0.25 mg/kg) increases
pilocarpine-induced yawning.
The yawning induced by ACTH-MSH peptides and
dopamine receptor agonists is abolished by
hypophysectomy but not by neonatal monosodium
glutamate treatment, which depletes brain
opiomelanocortin peptides. As a result of these
findings, it has been suggested that peripheral
and central ACTH-MSH peptides are not involved
in the yawning response to dopamine receptor
agonist. On the other hand, our results show
that adrenalectomy has effects similar to
hypophysectomy on YF, therefore, it can be
inferred that adrenal glands have an important
role in this behavior. There is no doubt
that the removal of the adrenal glands probably
alters several factors which may have an impact
on yawning, and therefore more studies are
needed to fully understand this complex
behavior. Nonetheless, our study points to the
important role of the adrenal glands and
glucocorticoids in the control of yawning.
