Introduction : For many years our
group has been evaluating the behavioral and
neuropharmacological consequences of paradoxical
sleep (PS) deprivation. The single platform
technique, developed by Jouvet et al., induces
an increase in both relative and absolute
adrenal weights and in plasma corticosterone
levels (data not published), indicating its
stressful nature. Moreover, several of the
techniques employed for PS deprivation possess
in their nature some sort or degree of stress.
In an attempt to investigate the influence of
stress on the effects of PS deprivation
technique, Silva et al. exposed rats to four
different manipulations: PS deprivation,
immobilization, forced swimming, and foot shock
for 3 days. Following this period,
apomorphine-induced aggressiveness was compared
among the groups. Increased aggressiveness was
observed in PS deprivation and foot shock
groups.
Among the behaviors altered by PS
deprivation, yawning is particularly
interesting, because it can be elicited by
several cholinergic (AChergic) agonists, by low
doses of dopaminergic (DAergic) agonists, and
polypeptides such as a-MSH and ACTH, suggesting
there are different neurotransmitter systems
involved in the modulation of this
behavior.
Ninety-six h of PS deprivation result in an
almost complete suppression of yawning induced
by DAergic and AChergic agonists. Since activity
of both neurotransmitter systems is also altered
by stress we examined the effects of other
widely used stressors on drug-induced yawning.
Animals were chronically exposed to
immobilization, forced swimming or mescapable
shock (Experiment 1 ) or acutely submitted to
forced swimming or inescapable shock (Experiment
2). Following stress exposure, yawning induced
by DAergic and AChergic drugs was evaluated.
[...]
Discussion : The results of the
prescrit study show that immobilization was the
only stressor that consistently suppressed
drug-induced yawning. Chronic foot shock and
swimming, on contrary, promoted an increase or
no change in number of yawns. This effect was
not due to the last stress session, as shown by
results of Experiment 2, in which acute exposure
to the latter stressors did not result in change
of yawning frequency. Evidence from our and
other laboratories suggests that constant
chronic stress suppresses drug-induced yawning,
regardless the modality of stress. Thus, PS
deprivation induced by the single platform
technique suppresses apomorphine, pilocarpine,
and physostigmine-induced yawning, suggesting
this manipulation renders both DAergic
presynaptic and AChergic postsynaptic receptors
subsensitive to their agonists. Nunes Jr. et al.
PS deprived rats using the multiple platform
technique (in this case, 10 animals are placed
on top of 18 platforms, 6 cm wide, placed 10 cm
apart, inside a large water tank, which
dimensions are 125 x 45 X 36 cm, thus enabling
the animals to jump from one plarform to
another), therefore preventing immobilization
and social isolation. Yet, the authors
replicated the effects of the single platformi
technique-induced deprivation on yawning
behavior. In addition, Bourson and Moser
reported suppression of apomorphine- and
physostigmine-induced yawning in animals
isolated for 7 days.
Based on the above mentioned results it is
possible to hypothesize that to suppress
drug-induced yawning, animals must be exposed to
stress in a constant fashion. To reinforce this
notion, in the present study, chronic foot shock
and swimming were employed intermittently during
96 h and resulted in increased or no change ni
number of yawns. It appears as though existence
of interstressor intervals differentially
modulates neuronal and neuroendocrine
functions.Yawning is believed to be mediated by
a balance between DAergic and AChergic neurons .
The former, most likely the nigrostriatal
pathway, exerts an inhibitory action on the
latter, most likely striatal AChergic neurons.
Thus, yawning is elicited by low doses of
aponiorphine (probably acting at presynaptic
receptor level) and AChergic drugs that act at
the postsynaptic receptor. It has been
demonstrated that both acute and chronic
intermittent stress result in increase of ACh
release and of high affinity choline uptake by
presynaptic membranes of' the septo-hippocampal
system, a system believed to be involved in
yawning behavior.
However, augmented binding of muscarinic
AChergic receptors can be observed only after
chronic intermittent stress. A downregulation of
M2 muscarinic receptors was demonstrated
following 96 h of PS deprivation by the multiple
platform technique. Acute stress, and even acute
treatment with ACTH and corticosterone do not
produce changes in receptor binding, although
increased sensitivity, but not number, of
muscarmic receptors is reported at 1 and 48 h
following a 2 h immobilization period in some
brain regions. Overail, the data suggest that
changes in receptor sensitivity require longer
exposure to stress and/or longer time span
between stress onset and functional evaluation
of these receptors, since we did not find
changes in yawning 6 h following 1 h of either
foot shock or swimming (Exp. 2). We cannot
ignore, however, that failure in showing
statistical differences in Exp. 2 could be due
to differences in control groups among time
intervals, Within the framework- of' the present
experiment is not possible to explain such
differences.
In conclusion, the results of the present
study indicate yawning can be altered in a
stressor-specific manner. Immobilization, the
only stressor to which animals were constantly
exposed, was also the only one that resulted in
yawning suppression. An opposite effect was
observed following stressors in which long
intersession intervals were present.
-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
-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
-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
-Moyaho A,
Valencia J Grooming and yawning trace
adjustment to unfamiliar environments in
laboratory Sprague-Dawley rats J Comp Psychol
2002; 116; 3; 263-269
-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; 32-38
-Tufik S et
al Effects of stress on drug induced yawning
Physiol Behav 1995; 58; 1; 1881-1884
