AG Nasello, AS Sassatani, FS Ferreira, LF
Felicio, CA Tieppo
Departamento de
Ciências Fisiologicas da Faculdade de
Ciências Médicas da Santa Casa de
Sào Paulo Brazil
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
Introduction : Light intensity
influences almost all physiological and
behavioral processes. These influences are
responsible for some biological rhythms,
especially those related to the light-dark
cycle, with circadian rhythm being one of the
better known. It is classically recognized that
the release of neurotransmitters and the
secretion of hormones vary according to
circadian rhythms. These variations are among
the major causes of physiological and behavioral
modifications induced by light intensity
variations. The oestrous cycle of some
laboratory and farm animal species can be
synchronized by manipulation of photoperiodism.
In rodents, core body temperature and motor
activity are known to be well synchronized with
each other under 12-h light- 12-h dark and 12-h
light-light and 12-h darkdark conditions. During
lactation and during critical postnatal periods,
variations of light conditions modify the
circadian organisation of motor activity of
adult animal. There is a relationship between
circadian changes in spontaneous motor activity
and dorsal vs. ventral striatal dopamine
neurotransmission. Circadian fluctuations in
dopamine levels and receptor density, as well as
in alpha and beta-adrenergic receptor density in
rat brain, have also been described.
Photoperiodism also modifies drug effects and
their pharmacokinetics.
To study the effects of light intensity on
variables such as sex, stress conditions, age,
and strains may be of crucial importance. In
humans, although they have increasingly
insulated themselves from natural cycles of
light or darkness, some psychiatric syndromes
are related to or influenced by photoperiod and
light intensity. Seasonal affective disorder, a
mood disorder involving a recurring autumn
and/or winter depression may be treated by
phototherapy but this treatment is not
beneficial to normal individuals. In
non-seasonal depression, mood typically
fluctuates daily, with improvement over the
course of the day, influenced by light
intensity. Sudden darkness in rats is equivalent
to sudden lightness in humans. Phototherapy,
that is, submission of patients to sudden
increase of light intensity is one of the
treatments for depression and in particular, for
seasonal affective disorders. On the other hand,
this kind of treatment is not favorable for
normal individuals. Bright light interventions
tended to make normal elderly women feel
worse-more irritable, anxious, and agitated. In
other words, sudden light changes may be useful
in the treatment of some psychiatric and
neurological disorders or may impair others
depending on the mechanisms involved.
Although there is a large database relating
light intensity and behaviour, studies on sudden
darkness are less frequent. In the past, this
model has been used to evaluate peptide action
on dopaminergic systems. In a previous paper, it
bas been described that sudden darkness
increases general motor activity and it
diminishes habituation, fear, and anxiety. In
addition, as it has been described, sudden
darkness can be used as an experimental tool to
modify behavioral parameters without using
drugs. The aim of the present study was to
investigate the role of dopaminergic mechanisms
involved in the effects of sudden darkness using
a pharmacological approach. For this purpose, we
evaluated the effects of sudden darkness on
behaviors elicited by a large scope of
apomorphine (APO) doses, 0.05 mg/kg being the
lowest and 0.6 mg/kg being the highest, such as
yawning-penile erection syndrome (YES), general
activity, and stereotypy.
Discussion : Sudden darkness is able
to induce an outstanding increase of general
activity. The mechanisms underlying this
phenomenon are unknown. The behavioral changes
are so fast that only changes in
neurotransmission may be responsible for them.
We focused on dopaminergic systems because there
is a direct relation between general activity
and dopaminergic activity and responses to light
intensity changes are often related to
dopamine.
The behavioral responses to dopaminergic
receptor stimulation are well known. Low
doses of dopamine elicited yawning,
suppression of exploration, and penile erection
(YES). These are behavioral patterns that occur
concomitantly under some conditions. After that,
by progressively increasing dopamine
concentrations, a typical bell-staped
dose-response curve of general motor activity is
observed, i.e., hypo-hyper-hypo-mobility.
In other words, the YES is reduced,
exploration starts and continues to increase
until it totally replaces the YES, and then
maximal general activity is observed. Later on,
mobility starts to decrease and is replaced with
stereotyped behaviors until maximal stereotypy
is reached. The same prototype of behavioral
responses is obtained using APO, a full and
nonspecific dopaminergic agonist.
In the present paper, we showed that sudden
darkness was able to, modify some spontaneous
behaviors and also modulated several APO-induced
behavioral effects. We used APO in a dose range
between 0.05 and 0.60 mg/kg.
The influence of sudden darkness on the
effects of pre(0.05 and 0.1 mg/kg) and
post-synaptic doses (0.25, 0.45 and 0.6 mg/kg)
of APO was tested. Pre-synaptic doses were
assayed in YES (0.05 and 0. 1 mgikg) and motor
activity (0.05 mg/kg). Post-synaptic doses were
evaluated in motor activity (0.25 mg/kg) and
stereotyped behaviour (0.45 and 0.6 mg/kg).
Spontaneous total and genital grooming of male
and female rats was also recorded.
The YES is a physiological response that can
be used as an experimental tool to elucidate
mechanisms of actions of drugs and hormones.
Although the syndrome is related to various
neurotransmitters, dopamine is particularly
involved. There is controversy about the subtype
of dopamine receptor involved. The D2 subtype
appears to be the main receptor involved, but
the participation of the D1 receptor alone or
simultaneously activated with the D2 receptor
cannot be dismissed. Moreover, expression of YES
may be due to the stimulation of D2
autoreceptors of nigrostriatal dopaminergic
neurons, although we should also consider the D2
post-synaptic stimulation of the paraventricular
nucleus of the hypothalamus. In any case, this
syndrome only becomes visible with the lowest
stimulation of dopaminergic systems. Sudden
darkness diminished total yawns obtained with
0.05 and 0. 1 mg/kg of APO in a dose-related
manner. These facts suggest an activation of the
dopamine responses involved that could shift
these responses to mobility. No other parameter
of YES was modified.
Taken together, these results may indicate
that, albeit triggered by the same stimuli,
different pathways are involved in yawning and
penile erection, as proposed by Gamberini et al.
The effect of sudden darkness on APO-induced
yawning was the opposite of that observed
when this parameter was recorded during the dark
time of the day. This suggests that the effects
of abrupt changes in light intensity differ from
those of light conditions corresponding to the
circadian rhythm. One of the factors included in
the YES is genital grooming. In this situation,
genital grooming is a consequence of penile
erection and cannot be correlated with
spontaneous grooming. Like all the other
variables linked to penile erection, it was not
modified, by sudden darkness. In almost all
species of animals, spontaneous grooming has
important physiological functions and a
significant meaning in social interaction and
social organization. It is also a factor related
to sex. Dopamine is implicated in the expression
of this behavior with different participations
of its receptor subtypes. Sudden darkness
increased spontaneous total and genital grooming
of male rats but had no effect on either kind of
grooming of female rats. This sexual
dissimilarity can be explained by the tact that
sudden darkness increased motor activity in
female rats more than in male rats. That is,
part of the time spent in locomotion by female
rats is substituted by grooming in male
rats.
Spontaneous motor activity is the result of
the interactions of a myriad of peripheral and
central variables. Among them, dopamine is
certainly one of the most important. Sudden
darkness augmented locomotion and rearing,
diminished immobility but did not modify total
groommg, as previously reported. Hypo-mobility
induced by 0.05 mg/kg was not altered by sudden
darkness. However, the increase in locomotion
and rearing and the decrease in immobility time
observed under sudden darkness, even though
nonsignificant, may be correlated with the
decrease in yawning observed with the same APO
dose.
Animals treated with 0.25 mg/kg were clearly
divided into two groups, i.e., hypo- and
hyper-responsive. Under light conditions, both
groups were different from the control but did
not differ from one another. Sudden darkness
enhanced the locomotion of the hypo-responsive
group compared to control. Sudden darkness
reduced the locomotion of hyper-responsive
animals, a tact that may be explained by
overstimulation of dopaminergic systems that
shifts general activity to stereotyped
behaviors. Locomotion responses to sudden
darkness by hypo- and hyper-responsive rats
suggest that sudden darkness potentiated the
responses to APO. Rearing and grooming were
reduced in both groups; in hypo-reactive rats,
this may perhaps have been due to the increase
of locomotion and in hyper-reactive animals,
iît may have been due te, the surge of
stereotyped behaviors. No differences were
observed in immobility duration.
Stereotypy is the major behavioral response
induced by dopaminergic stimulation. The
circadian lightdark cycle modified stereotypy
with highest responses at 1300 and 1700 h.
Stereotyped behaviors induced by 0.45 and 0.60
mg/kg of APO were similar and were not modified
by sudden darkness. Probably, physiological
changes elicited by sudden darkness are unable
to modify this strong pharmacological
response.
In a previous paper, we proposed sudden
darkness as an experimental tool to modify motor
activity and anxiety. Now, we show that other
behaviors can be modulated by sudden darkness.
Animal models based on spontaneous behavior or
ethologically based models may be more sensitive
to behavioral responses.
Our results may be due to a sudden
darkness-induced physiological release of
dopamine. This hypothesis is based on data
showing that sudden darkness diminishes
pre-synaptic responses to APO and increases
lower post-synaptic responses such as motor
activity without modifying higher post-synaptic
responses such as stereotyped behavior.
Experiments to confirm this hypothesis by
microdialysis procedures are being done in our
laboratories. Physiological release of dopamine
may be useful in the treatment of psychiatric
and neurological disorders or may impair others
depending on dopaminergic mechanisms involved in
the pathophysiology of the diseases. It must be
taken into account that sudden darkness in rats
is equivalent to sudden lightness in
humans.
-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
-Seki Y, Y
Nakatani, et al Light induces cortical
activation and yawning in rat Behav Brain Res
2003; 140; 1-2; 65-73
-Gamberini
MT, Bolognesi ML, Nasello AG. The modulatory
role of M2 muscarinic receptor on
apomorphine-induced yawning and genital
grooming. Neurosci Lett. 2012
