Treatment
with dexamethasone alters yawning behavior
induced by cholinergic but not dopaminergic
agonist
Hipolide DC, Lobo LL, De Medeiros R, Neumann
B, Tufik S
department of psychobiology,
Universidade de Sao Paulo, rua Botucatu, 862
Andar, SP 04034-062 Sao PAulo Bresil
Although the physiological significance of
yawning is still not clear, it can be used as a
model for understanding how various CNS
structures interact to initiate and execute a
behavior. Previous studies have established that
yawning can be elicited in experimental animals
by cholinomimetic drugs and by dopamine
agonists. It can be also inhibited by both
dopamine D2-receptor and muscarinic receptor
antagonists, thereby indicating that the
behavior involves dopaminergic and cholinergic
activation. Findings concerning yawning
behaviorafter
paradoxical sleep deprivation (PSD) are
particularly interesting, because there is an
almost complete suppression of yawning
induced by dopaminergic and cholinergic
agonists. However, it is not well established
whether suppression of yawning after PSD is due
to absence of this sleep stage or the result of
the stress-related techniques employed for PSD.
Recently, we have reporied that immobilization,
which is associated with the "flower-pot" PSD
procedure, alters drug-induced yawning. Several
neurotransmitters and neuropeptides have been
documented to elicit or modulate yawning
behavior, which involves the activation of
dopaminergic-cholinergic linked neuronal
systems.
It is generally admitted that activity of
dopaminergic and cholinergic systems is altered
by physical stress and/or by pharmacological
agents that mimic stress response. Numerous
observations suggest that glucocorticoids, the
final product of activation of the
hypothalamus-pituitaryadrenal axis, might be one
factor capable of increasing the activity of
these systems.
Because stressful manipulations have been
reported to modify drug-induced yawning, the
present study investigated the effects of single
and repeated administration with a synthetic
glucocorticoid, dexamethasone (DEXA) on
yawning behavior. DEXA is primarily involved
with the activation of glucocorticoid receptors
(GR), and is, therefore, used to stimulate
stress-related glucocorticoid actions.
[...]
DISCUSSION
The present study shows that single and
repeated treatments with dexamethasone (DEXA)
have opposite effects on pilocarpine-induced
yawning, whereas it had none on
apomorphine-induced yawning.
Induction of yawning behavior appears to be
dependent on a balance between dopaminergic and
cholinergic systems. Although the hypothesis
that yawning is elicited by dopamine inhibition
and, consequently, acetylcholine activation is
supported by several studies, there is a
controversy about the mechanisms involved in
this behavior.
There is accumulating evidence that
glucocorticoids do interact with the
dopaminergic system and facilitate dopamine
release and increase sensitivity of dopaminergic
receptors. In the present data, single and
repeated DEXA treatment did not modify
apomorphine-induced yawning. In contrast,
previous reports showed that constant chronic
stress suppresses apomorphine-induced yawning,
regardless of the modality of stress. With
respect to the discrepancy between the present
results and the above-mentioned data, it is
important to note that two types of
corticosteroid receptors are distinguished in
rat brain . Inoue and Koyama have found that
chronic corticosterone but not DEXA treatment
increases the levels of homovanillic acid (HVA)
in medial prefrontal cortex. Furthermore,
another possibility is that the dose of DEXA
used in the present study was not sufficient to
produce activation of the dopaminergic system.
Previous studies have shown modification of the
dopaminergic systern using doses higher than
0.25 mg/kg.
Some studies suggest a stress-specific
change of dopaminergic function dependent on the
brain area examined. For example, immobilization
induces an increase in dopamine release and its
metabolites concentration in nucleus accumbens
and frontal cortex, but not in nucleus caudatum.
Recently, Cabib and Puglisiallegra reported that
the mesolimbic and the mesocortical dopamine
systems adapt differently to repeated exposure
to a stressor. Because yawning bas been
associated with septal and striatal dopaminergic
autoreceptors, it is possible that DEXA
treatment does not modify the dopaminergic
transmission in this pathway. Although Gilad
observed reduction of dopamine uptake in
synaptosomes from both septal and striatal
regions of the brain, it is important to note
that this author used another synthetic
glucocorticoid.
Data of glucocorticoid effects on
cholinergic transmission are scarce. Only in the
last years a number of studies has focused on
the importance of the cholinergie function in
the neurophysiology of stress with particular
reference to the septo-hippocampal cholinergie
pathway, a system believed to be involved in
yawning behavior. The present study shows that
single administration of DEXA increased the
number of yawns induced by pilocarpine. It is
possible that concomitant administration of a
single dose of DEXA and pilocarpine may act
synergistically, potentiating the effects of the
latter on yawning. However, we have demonstrated
that acute immobilization, footshock, and
swimming do not result in significant alteration
of pilocarpine -induced yawning, although there
was a clear tendency towards increase of yawning
frequency in stressed animals. It is important
to consider that endogenous release of
corticosterone after stress (ie.,
immobilization) stimulates both MR and GR
receptors, whereas DEXA bas high affinity for
GR. There is evidence showing that short periods
of stress do not alter the characteristic of the
muscarinic receptor. Therefore, the mechanism
that mediates the increase of yawning response
after a single administration of DEXA may
involve the release of acetylcholine and not
changes in the sensitivity of cholinergic
receptors.
Conversely, repeated treatment with DEXA
resulted in a reduced number of
pilocarpine-induced yawning. These finding
confirm and extend our previous data that
chronic immobilization suppresses
cholinergic-induced yawning. Bccause repeated
stress leads to habituation and adaptation
processes, it is possible that repeated
administration of DEXA produced a subsensitivity
of postsynaptic cholinergic receptors.
Consistent with this notion, it has been
proposed that chronic stressful manipulations
change cholinergie receptor sensitivity.
The opposite effects produced by single and
repeated DEXA treatment on pilocarpine-induced
yawning observed in the present study may be
associated with the changes in muscarinic
receptor sensitivity. Another alternative
hypothesis is the balance between GR and MR
receptors. The continuous stimulation of GRs
will result in an adaptive reduction of GRs and
an increase of MRs for maintenance of balance
between those receptors.
For many years we have been evaluating the
behavioral and neuropharmacological consequences
of paradoxical sleep deprivation (PSD). Repeated
administration of DEXA and PSD has the same
effect on pilocarpine-induced yawning. It is
possible that PSD effects on yawning are
mediated by the stressful conditions produced by
the procedure itself. The present findings show
that dopaminergic and cholinergic systems
differently altered by treatment with DEXA, in
terms of yawning behavior.
Gessa GL
Stretchings and yawnings induced by
adrenocorticotrophic hormone Nature 23/07/1966;
5047; 426-427
Gessa GL
Stretching and yawning movements after
intracerebral injection of ACTH Revue Canadienne
Bioliologie; 1967, 26, 3, 229-236
Kimura H,
Yamada K, Nagashima M, Matsumoto S, Ishii Y,
Yoshida S, Fujii K, Furukawa T Role of
adrenergic neuronal activity in the yawning
induced by tacrine and NIK-247 in rats.
Pharmacol Biochem Behav 1992; 43; 4; 985-91
Kimura
H, Yamada K, Nagashima M, Furukawa T
Involvement of catecholamine receptor activities
in modulating the incidence of yawning in
rats.Pharmacol Biochem Behav 1996; 53; 4;
1017-21
Laing J, Ogilvie R
EEG correlats of yawning during sleep onset
Sleep Research 1988; 17; 98
Serra
G , Collu M and Gessa GL Yawning is elicited
by D2 dopamine agonists but is blocked by D1
antagonist Psychopharmacology 1987; 91;
330-337
Serra G,
Gessa GL Hypophysectomy prevents yawning and
penile erection but not hypomotility induced by
apomorphine Pharmacology Biochemistry &
Behavior 1983; 19; 917-919
Serra
G et al Cycloheximide prevents apomporphine
induced yawning, penile erection and genital
grooming in rats European Journal of
Pharmacology 1983; 86; 279-282
Stahle
L Do autoreceptors mediate dopamine
agonist-induced yawning and suppression of
exploration ? a critical review.
Psychopharmacology 1992; 106; 1-13
-Hipolide DC; Lobo
LL; De Medeiros R; Neumann B; Tufik S
Treatment with dexamethasone alters yawning
behavior induced by cholinergic but not
dopaminergic agonist. Physiol Behav 1999; 65;
4-5; 829-32
-Hipolide
DC, Tufik S Paradoxical sleep deprivation in
female rats alters drug-induced behaviors
Physiol Behav. 1995; 57; 6; 1139-1143
-Mogilnicka E,
Klimek V Drugs affecting dopamine neurons
and yawning behavior. Pharmacol Biochem Behav
1977; 7; 303-305
-Molgilnicka
E REM sleep deprivation changes behavioral
response to catecholaminergic and serotoninergic
receptor activation in rats Pharmacol Biochem
Behav 1981; 15; 1; 149-151
-Neumann BG,
Troncone LR, Braz S, Tufik S Modifications
on dopaminergic and cholinergic systems induced
by the water tank technique: analysis through
yawning behavior Arch Int Pharmacodyn Ther 1990;
308; 32-8
-Stoessl
AJ Effects of ageing on the behavioural
responses to dopamine agonists: decreased
yawning and locomotion, but increased stereotypy
Brain Research 1989; 495; 20-30
-Tufik S et
al Effects of stress on drug induced yawning
Physiology & behavior 1995; 58; 1;
1881-184
-Tufik S
Does REM sleep deprivation induce subsensitivity
of presynaptic dopamine or postsynaptic
acetylcholine receptors in the rat brain?
European Journal of Pharrnacology 1987; 140;
215-219
