Yawning, suppression of exploration, and
penile erection are behavioral patterns that
occur concomitantly under some conditions. These
behaviors are elicited by low doses of the
dopamine (DA) receptor agonist apomorphine
(APO). It also has been proposed that they may
be useful as a behavioral model for negative
symptoms of schizophrenia. These three
behavioral parameters are also elicited by low
doses of other DA agonists. The clinical
usefulness of APO as well as other DA agonists
on schizophrenia and hyperkinetic disorders has
also been reported. Yawning alone or associated
with stretching is considered as an ancestral
vestige, surviving throughout the evolution,
that subserves the purposes of arousal.
It has been suggested that dopaminergic
mechanisms controlling yawning are central
because domperidone, a DA antagonist that does
not cross the blood-brain barrier, has no effect
on this behavior. There are several reports
about the central nucleus and circuits involved
in yawing expression. There are also many
studies showing how this behavior is influenced
by drugs such as pilocarpine, physostigmine,
scopolamine, haloperidol, sulpiride,
remoxipride, rnetoclopramide, morphine,
buspirone and others, as well as by hormones
like ACTH, oxytocin, LHRH, and a-MSH. In
addition, it is modified by REM sleep
deprivation. However, very little is known about
the influence of feeding and time of day on the
modulation of this behavior.
To further our knowledge conceming the
influence of these physiological variables, this
study was designed to assess the influence of
24- and 48-h fasting and light-dark cycle on the
expression of APO-induced yawning. [...]
Gamberini
MT, Bolognesi ML, Nasello AG. The modulatory
role of M2 muscarinic receptor on
apomorphine-induced yawning and genital
grooming. Neuroscience Letters 2012;
531:91-95
-Gamberini
MT, Gamberini MC, Nasello AG. Involvement of
dopaminergic and cholinergic pathways in the
induction of yawning and genital grooming by the
aqueous extract of Saccharum officinarum L.
(sugarcane) in rats. Neuroscience Letters
2015;584:270-275
-Naselo A,
Tieppo C, Felicio L Apomorphine induced
yawning in the rat : influence of fasting and
time of day Physiology & Behavior
1995;57(5):967-971
-Nasello
AG et al Modulation by sudden darkness of
apomorphine-induced behavioral responses
Physiology & Behavior 2003;78:521-525
Discussion :
The importance of studying yawning
behavior is clear from the point of view of
physiological responses or as an experimental
tool to elucidate the mechanisms of actions of
drugs and hormones. In addition, this
behavior serves as a paradigm for some diseases
and for clinical applications of low doses of
dopamine agonists.
Our results show that: 1) 100 µg/kg is a
more effective dose than 50 or 150 Mg/kg APO; 2)
24-h or 48-h fasting significantly reduce
APO-induced yawning-, 3) during the dark period
APOinduced yawning is significantly more intense
than during the light period.
APO doses ranging from 30 to 250 µg/kg
are reported as being able to elicit yawning
behavior. The purpose of our first experiment
was to determine the most appropriate dose of
APO to induce yawning in rats in our laboratory
conditions. Dose-response and time-response
curves were built; 100 µg/kg was the most
effective dose. The doses of 50 and 150 µg
induced lower responses: the results obtained
with the lowest dose may be because 50
µg/kg is under the dose necessary for a
maximal response whereas 150 µg/kg APO was
too high and induced stereotypy, which is a
behavior that excludes yawning. The maximal
response occurred in the 10-20min interval for
the doses of 50 and 100 µg/kg and in the
2030-min interval for 150 µg/kg. Because
the highest dose elicited stereotyped behavior,
it may be necessary to wait for the drug to be
metabolized for the optimum yawninginducing dose
to be achieved. Thus, we chose 100 µg/kg
APO for the following experiments.
Distinct areas of the brain are modified
differently by fasting. Fasting drastically
diminished the response to APO: 24-h food
deprivation is enough to modify this behavior.
The 48-h food-deprivation effects on yawning
were not different from the 24-h fasting
effects. Yawning decrease seems to bc maximal at
24-h of food deprivation. One-hour feeding
before the test does not reverse this reduction,
suggesting that this behavioral change is
persistent and not rapidly reversed by a meal.
On the other hand, we have previously
demonstrated that fasting followed by previous
meal modifies the expression of 100 µg/kg
APO-induced behaviors such as genital grooming
and pende erection . The present results show
that a previous meal reduces yawning more
intensely in 48-h than in 24-h food-deprived
rats. Ibis finding suggests that, in some
physiological states, a meal can inhibit
yawning.
The dark period is the time for physiological
arousal for rats; during this period there is an
increase in some behaviors, such as motor
activity and sexual behavior. We observed that
during the dark period the yawning response to
APO, a dopamine agonist, was significantly
higher than during the light period. Ilis result
suggests that dopaminergic responses are
increased during the dark period. This increase
in APO-induced yawning may be due to a decrease
in the activity of dopamine neurons or tu an
increase in the dopamine receptors' sensitivity,
or both. Fasting increases the DA turnover in
the hippocampus but not in the hypothalamus,
striatum, and cortex. Yawning is not telated te,
extracellular striatal levels of DA. It can be
speculated that the DA receptors' sensitivity
may be modified during fasting and the dark
peried.
The role that each of the DA receptor subtype
activation plays on these behaviors is not well
established. Dopamine D2 autoreceptor used to be
considered as being the only DA teceptor
involved in yawning and pende erection syndrome;
other authors considered the involvement of D,
receptors (9,19,42) or a simultaneous activation
of Dl and D2 receptors. More recently,
accumulating evidence suggests that a special
subpopulation of D2 postsynaptic receptors,
possibly D3 subclass, may play a relevant role
in these dopaminergic behaviors.
The sensitivity of some DA receptors is also
modified by a large number of manipulations
[e.g., the response to APO is modified in
the deprivation of long-term treatment with
bromopride, a D2 antagonist]; this response
is also modified in offspring of dams treated
with bromopride (l 1) or quinpirole (20) during
pregnancy and/or lactation. Changes in APO
tesponse might also depend on mechanisms beyond
or independent of DA receptors [e.g.,
acetylcholine, oxcytocin, ACTH, LHRH, nitric
oxide, and a-MSH.
Our results suggest that fasting and time of
day may modify the DA receptors' sensitivity in
the brain areas involved with yawning. This
finding has many practical consequences, because
it has been reported that low doses of DA
agonists are effective in various psychiatric
conditions like schizophrenia and Gille dela
Tourette's disease, as well as neurological
disorders such as Huntington chorea, tardive
dyskinesia, and torticollis. Further study are
necessary to verify how 24-h fasting and the
dark period differentially modify the activity
od dopaminergic systems.
Gamberini
MT, Bolognesi ML, Nasello AG. The modulatory
role of M2 muscarinic receptor on
apomorphine-induced yawning and genital
grooming. Neurosci Lett. 2012