Department of psychobiology,
Universidade de Sao Paulo, rua Botucatu, 862
Andar, SP 04034-062 Sao Paulo Bresil
Abstract : Central administration of
ACTH in rats induces yawning and stretching. In
order to study the effects of REM sleep
deprivation on ACTH-induced yawning, the peptide
was injected immediately after the REM sleep
deprivation period or 24 h later. REM sleep
deprivation impaired ACTH-induced yawning, but
after a 24-hour recovery period, rats displayed
a number of yawns similar to those in control
animals. Implications for an involvement of
dopaminergic and mainly cholinergic systems are
discussed.
Introduction : Yawning behavior can be
induced in rats by systemic administration of
very small doses of apomorphine or other
dopaminergic agonists and cholinergic agonists,
as well as by intracerebral injection of ACTH or
some of its analogues. This syndrome, which is
also characterized by stretching and penile
erection, is suggested to be a behavioral
consequence of the involvement of dopaminergic
and cholinergic systems.
Although the exact mechanisms that
participate in the stretching-yawning syndrome
(SYS) have not yet been completely elucidated,
it appears that the central cholinergic
muscarinic receptors are of fundamental
importance. Atropine and scopolamine, both
central cholinergie antagonists, block the SYS
induced either by dopaminergic and cholinergie
agonists or by ACTH and its analogues. Recently,
Wood et al. have proposed that the
septal-hippocampal cholinergic neurons are
necessary to elicit the SYS following ACTH or
a-MSH since intraventricular injection of these
neuropeptides increases the acetylcholine
turnover rate in the hippocampus of rats.
We have recently demonstrated that rats
submitted to 96 h of REM sleep deprivation
show a great reduction of yawnings induced
by apomorphire (direct dopaminergic agonist),
physostigmine and pilocarpine (indirect and
direct cholinergic agonists, respectively) when
they are tested immediately after the end of the
deprivation period. However, if the animals are
allowed to rest for 24 h after the period of
sleep deprivation, the yawning induced by
pilocarpine returns to control values, whereas
apomorphine- and physostigmine-induced yawning
is still reduced [unpublished. data].
This suggests that REM sleep deprivation affects
the dopaminergic and cholinergic systems in
different ways. Because of,this and since the
mechanism through which ACTH induces the SYS is
attributed to the activation of muscarinic
receptors, the present study intended to verify
the effects of REM sleep deprivation upon
yawning induced by ACTH, immediately after the
end of the deprivation period, and after 24 h of
recovery in order to further the understanding
of the systems involved in REM sleep deprivation
and yawning. [...]
Discussion : With regard to the
interaction of dopaminergic-cholinergic neurons
and yawning, dopaminergic neurons have been
reported to play an inhibitory role in the
control of the septal-hippocampal cholinergic
neurons. Also, there is an indication that the
cholinergic system of the hippocampus
participates in the SYS induced by ACTH and
a-MSH, since a 2-fold elevation of the
hippocampal turnover rate of acetylcholine has
been observed after the intraventricular
administration of these polypeptides, being
suggestive of an involvement of muscarinic
acetylcholine receptors. Furthermore, the SYS
induced by ACTH is inhibited by atropine and
scopolamine, both central cholinergic
antagonists, and also by the neuroleptic
chlorpromazine. Scopolamine also inhibited
yawning induced by apomorphine. Sulpiride, a
specific dopamine receptor blocker, antagonizes
apomorphine-induced yawning, but fails to affect
this behavior induced by ACTH, which suggests
that ACTH induces yawning by acting on neuronal
pathways different from those of dopamine
agonists. It has been described that lesions at
the paraventricular nucleus prevent
apomorphine-, but not ACTH-induced yawning,
leading once again to the relationship between
ACTH and acetylcholine during the display of
yawning.
It bas been reported that REM sleep
deprivation produces dopaminergic
supersensitivity, probably inducing a
cholinergic subsensitivity, which is also
observed after chronic administration of
haloperidol. Similarly, REM-sleep-deprived
animals show a reduced number of yawns in
response to apomorphine, pilocarpine and
physostigmine, suggesting a lowered
responsiveness of either dopaminergic and/or
cholinergic systems. It seems that chronic
haloperidol and probably REM sleep deprivation
act initially by blocking the dopaminergic
system and consequently releasing the
cholinergic neurons from the dopaminergic
inhibition. Indeed, it has been demonstrated in
our laboratory that the recovery does not occur
simultaneously in dopaminergic and cholinergic
systems (see Introduction).
It is widely accepted that stressful
situations provoke a rise in
hypothalamo-hypophysial-adrenal axis activity,
and recent data suggest that adrenocortical
hormones modulate dopaminergic receptor
function. It must be considered that REM sleep
deprivation is a stressful procedure, and it is
conceivable that during this treatment there is
an intense production and release of ACTH,
leading to a decreased sensitivity to ACTH, and
a possible reduction in the number of
drug-induced yawns, since this behavior seems to
depend on an entire chain of systems
(ACTH-acetylcholine-dopamine).
The delayed onset of the yawning, which was
observed alternating with pende erection and
stretching, is probably due to the slow
diffusion of the active material from the site
of injection into the sites of action
[4], or because ACTH acts through an
interaction with muscarinic acetylcholine
receptors, standing for the latency to trigger
the cholinergic system.
In summary, REM sleep deprivation for 96 h
lowers the responsiveness to
intracerebroventricular injection of ACTH, as
evidenced by yawning behavior. A 24-hour
recovery period after REM sleep deprivation
restores the system responsible for the
displaying of yawning after the central
administration of ACTH. Together with the data
obtained by Wood et al. and Gower et all
suggesting an involvement of the acetylcholine
receptor after ACTH treatment, it seems
consistent to accept the hypothesis that
yawning is a behavior mediated through the
activation of cholinergic neurons.
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