- ABSTRACT
- Yawning, associated with genital grooming,
is a physiological response that may be used for
elucidating the mechanism of action of
drugs.
-
- Preliminary analysis showed that aqueous
extract (AE) of Saccharum induced yawns in rats.
So, we aimed to quantify these behavioral
responses and investigate the pharmacological
mechanisms involved in these actions.
-
- During 120min, after AE administration, the
yawns and the genital grooming were quantified
at 10min intervals. Since dopaminergic and
cholinergic pathways are implied in these
responses, AE were evaluated in the presence of
haloperidol 0.5mg/kg and atropine 2mg/kg. AE
0.5g/kg increased the yawns, effect that was
blocked both by haloperidol and atropine.
-
- Genital grooming could only be stimulated by
AE 0.5g/kg when dopaminergic receptors were
blocked by haloperidol.
-
- However, it was inhibited when atropine was
previously administered. So, we demonstrated a
central action of Saccharum and it was
postulated that neural circuits with the
participation of dopaminergic and cholinergic
pathways are involved.
-
- The fact that AE is comprised of innumerous
compounds could justify the extract's distinct
responses. Also, we cannot disregard the
presence of different neural circuits that count
on the participation of dopaminergic and
cholinergic pathways and could be activated by
the same induction agent.
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
-
- Saccharum officinarum L., family Poacea, is
commonly known assugarcane. It is a perennial
grass whose root system is comprised of
adventitious and permanent roots. Its
cylindrical stalks can reach up to 6 m in height
and 6 cm in diameter. They are more or less
erect,arched at the base, knotty and slightly
thicker at the internodes, which are always
prominent, but irregularly spaced, yellow,
green, dark red, or violet in color (depending
on variety).
-
- The leaves are alternate or opposite,
distinct, flat, linear, acute at the apex, up to
140 cm in length and 6 cm in width, serrate,
rough, showing reticulate venation and a
protruding whitish midrib. The inflorescence of
sugarcane is a ramified, conoidal panicle with a
main stem, called the rachis, which is the
continuation of the previous stalk internode.
The fruits are dry and each one contains a
single seed.
-
- Sugarcane has a long history of safe use as
food for humans and animal feed. It is
commercially cultivated for use as a source of
sucrose and ethanol. Economic interest in
sugarcane has increased significantly in recent
years due to the increased worldwide demand for
sustainable energy production.
-
- Despite the fact thats ugarcane production
receives great attention due to its economic
value, it is important to point out that
Saccharum is also known in folk medicine for its
therapeutic properties. It is reported to act as
an antidote, antiseptic, antivinous,
bactericide, cardiotonic, demulcent, diuretic,
intoxicant, laxative, pectoral, piscicide,
refrigerant,stomachic and stimulant. It is a
folk remedy for arthritis, bed sores,boils,
cancer, colds, cough, diarrhea, dysentery, eyes,
fever, hiccups,inflammation, laryngitis,
opacity, penis, skin, sores, sore throat,spleen,
tumors, wounds, gonorrhea, and vaginal
discharges.
-
- Recent studies have demonstrated the plant's
antioxidant and anti-inflammatory activities,
besides its activity on both male and female
steroidogenesis.
-
- Our preliminary analysis of the general
effects induced in rats after administration of
the aqueous extract (AE) obtained from the
leaves of Saccharum officinarum L. revealed the
occurrence of yawns in rats.
-
- Yawning is a physiological, phylogenetically
ancient effect, which occurs with a low
frequency in humans and animals.Yawning is not
simple short duration reflex, but has a complex
spatiotemporal organization with facial and
respiratory components, amongst others.
Considering that yawning is also observed in
anencephalic newborns having solely the medulla
oblongata, the neural structures necessary for
yawning are possibly located in brainstem
regions that are either near or in the
respiratory and vasomotor centers, specially
those responsible for controlling facial
mimicry, chewing, deglutition, breathing, and
possibly stretching.
-
- This behavior may be spontaneously
triggered, or it can occur in the presence of
nausea, vomiting, tumors or brain injuries,
hemorrhage,encephalitis, or after several
neuropharmacological manipulations.
-
- Yawning can occur in an isolated manner, but
its occurrence is more frequently associated
with genital grooming, which is indicative that
common neural pathways may participate in
eliciting those responses. A series of
neurotransmitters and neuropeptides exert
central control over such behaviors. Amongst
endogenous mediators, the best-known ones are
dopamine; acetylcholine; oxytocin;
adrenocorticotropin (ACTH); melanocyte
stimulating hormone; serotonin; excitatory amino
acids; nitric oxide; and opioid peptides. Since
S. officinarum L. induced yawning in rats, the
current study aimed to proceed to the
pharmacological investigation of the plant's
aqueous extract in order to verify whether the
yawning was associated with genital grooming,
quantify these responses, and investigate the
possible pharmacological mechanisms of action
involved.
-
- Discussion
-
- Numerous studies have shown that different
agents such as several peptidergic hormones and
neurotransmitters induce concomitant yawning and
genital grooming. The involvement of the
dopaminergic system in the induction of yawning
and genital grooming becomes evident through the
administration of small doses of apomorphine, a
direct DA receptor agonist, with marked affinity
for DA D2-like (D2/D3/D4) receptors.
Furthermore, many dopaminergic antagonists, such
as haloperidol, have been shown to be effective
in inhibiting these behaviors. Also, the action
of acetylcholine in the control of yawning and
genital grooming has been well characterized by
cholinergic agonists and antagonists that induce
or abolish these behaviors. A large body of
evidence suggests a central role of cholinergic
neurons as a site of action for the induction of
cholinergic yawning and genital grooming, as
well as a common mediator of these responses
induced by a variety of pharmacological
mechanisms.
-
- Different areas of the Central Nervous
System have already been shown to elicit yawning
and genital grooming. In the striatum, a
particularly important area for the development
of those behaviors, a high density of
dopaminergic and cholinergic terminals exists
and these neurotransmitters have potent
interactions at multiple levels such as
presynaptic regulation of neurotransmitters and
postsynaptic effects in target cells,including
cholinergic neurons.
-
- Since preliminary evaluations conducted with
S. officinarum L.(sugarcane) revealed that the
administration of the plant's aqueous extract
(AE) induced yawning in rats, the current study
aimed to verify whether this behavior could be
associated with genital grooming, quantify such
responses, and investigate the possible
mechanisms of action involved. The oral
administration of the lowest dose of the extract
(AE0.5 g/kg) tested in the animals induced an
increase in the number of yawns as compared to
the control group. This effect was blocked both
by the dopaminergic antagonist, haloperidol, and
by the cholinergic antagonist, atropine. As to
genital grooming, this behavior could only be
effectively stimulated by the aqueous extract
when dopaminergic receptors had been blocked by
haloperidol. As observed with the yawns,
cholinergic pathways are involved. Potentiation
of the effect of the plant's extract when it was
associated with haloperidol was inhibited when
the cholinergic antagonist, atropine, had been
previously administered to the animals.
-
- In view of these results, not only have we
demonstrated a central action of the S.
officinarum L. (sugarcane) aqueous extract, but
also demonstrated that its mechanism of action
involves the activation of neural circuits with
the participation of dopaminergic and
cholinergic pathways. We must stress the fact
that we are analyzing the pharmacological action
of the aqueous extract, which is comprised of in
numerous chemical compounds that might interfere
with the results. This could justify the
distinct responses of the extract on yawning and
genital grooming that were observed in the
presence of haloperidol. In addition, we cannot
disregard the presence of distinct neural
circuits that could be activated by the same
induction agent, thus determining yawning and
genital grooming.
-
- As shown by the results obtained in the
current study, it is unquestionable that
pharmacologically active substances present in
S. officinarum L. affect the neural circuits
involved with yawning and genital grooming that
rely on the dopaminergic and cholinergic
systems' participation. The isolation of the
plant's active pharmaceutical compounds will
allow for a more precise elucidation of the
central mechanisms that determine the behavioral
responses evaluated. Dopaminergic and
cholinergic transmissions are involved in motor
and cognitive physiological processes.
Imbalances between these transmissions are found
in some disorders, such as Parkinson's disease,
Huntington's disease and schizophrenia. The
pharmacological strategies used for the
treatment of these diseases are based on
restoring the dopamine(DA)/acetylcholine(ACH)
balance in the CNS. In rats, the
interrelationship between dopaminergic and
cholinergic transmission can be explored through
behavioral tools such as yawning and genital
grooming.
-
- So, the pharmacological validation of plant
species such as S.officinarum L., long-used for
decades by the population, opens up new
perspectives in the development of therapeutic
agents for the treatment of serious diseases
related to the Central Nervous System.
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