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
