Yawning is a fixed innate motor
pattern that has been rather neglected in
experimental behavioral studies. Nevertheless,
some attention bas recently been focussed on its
tinderlying neurotransmitter mechanisms. From
results of experiments mainly performed in
infant rats, it bas been suggested that
central cholinergic synapses may play an
important role in relation to yawning, since
cholinomimetic drugs (physostigmine and
pilocarpine) greatly influence its frequency.
The responsible receptors seem to be of the
muscarinic type, because the yawning induicing
effect of the two above mentioned drugs is
blocked by scopolamine.
Other experiments performed in adult male
albino rats indicate that some dopaminergic (DA)
component might be present in yawning. Low doses
of systemically injected DA agonists
(apomorphine, piribedil, amphetamine,
nomifensine and L-DOPA) produce recurrent
episodes of yawning, responses which are
completely inhibited by spiperone.
As yawning seems to be commonly associated
with transitional phases in the sleep-waking
cycle, particularly with the state of
drowsiness preceding or following sleep, and
strong evidence links the serotonergic pathways
wilh slowwave sleep, it seemed worthwhile to
explore the possible participation of
serotonergic mechanisms in the induction or
modulation of yawning.
Method : Most of the experiments to
be reported were performed in infant (6-7
day-old) Wistar rats, born in the laboratory,
their age being estimated with an approximation
of +- 8 hours. All litters were reduced to eight
pups 24 to 36 hr after birth. The animals were
randornly distributed among experimental and
control groups. Yawning was induced by
intraperitoneal (IP) injection of physostigmine
(BDH) in doses of 0,15 mgKg . The animals were
placed in glass cylinders 18 cm in diameter, the
floor of which was covered with paper, and were
observed during one hour, paying attention only
to the number of yawns. Two drugs influencing
serotonergic synapses were used: Lu 10-171,
1-(3-dimenthyl-amino) propyl)- 1
-(p-fluorophenyl)-5-phtalancarbonitrile, (H.
Lundbeck and Co.) and metergoline (Farmitalia).
Lu 10-171 (citalopram DCI) is a very
potent and selective serotonin (5-HT) uptake
inhibitor. Some evidence indicates that
metergoline blocks selectively central 5-HT
receptors. All drugs were dissolved in saline
(0.9% NaCI) in such a way that the total volume
to be injected was equivalent to 0.01 ml/kg
bodyweight. Controls received IP injections of
the same volume of saline.
Results and discussion : Infant rats
injected with citalopram, in doses ranging from
0.1 to 10 mg/kg, do not exhibit any noteworthy
changes in overt behavior. If 40 min later they
receive physostigmine (0.15 mg/Kg) the latter
drug's yawning inducing effect is strongly
potentiated. The effect is statistically
significant with citalopram doses from 0.5 mg/kg
tipwards, reaching a four to eight-fold increase
in mean yawning frequency with the higher
doses.
Similar results, but at a lower level of
basal yawning frequency, were observed in young
(45-day-old) male rats, injected with
citalopram, in doses of 5 to 10 mg/kg, the
results being statistically significant for the
latter dose (MannWhitney U Test, p<0.05).
The potentiating effect of citalopram on
physostigmine induced yawning is counteracted by
metergoline (5 mg/Kg) when metergoline is
injected IP 30 min before receiving citalopram,
that is, 70 min before the yawning test with
physostigmine. It may be seen that metergoline
also reduces the number of yawns induced by
physostigmine in the control group, an effect
which even if not statistically significant
suggests the existance of a basal
serotonergic tone favouring the expression of
cholinomimetically induced yawning. This
suggestion was strengthened by the results of an
experiment with a higher dose of metergoline (10
mg/kg), with which the mean yawning level after
physostigmine was decreased to only 3
yawns/hour, that is, to 20 percent of the
original level, a result which is highly
significant (p<0.001, MannWhitney U
test).
As citalopram is a very selective inhibitor
of the 5-HT reuptake mechanisms, practically
devoid of inhibitory effects on NA reuptake or
on monoamine oxidase, and has only very weak
anticholinergic and antihistaminergic
properties, its potentiating effect on
physostigmine-induced yawning may reasonably be
ascribed to an increase
of serotonin in central nervous system synapses
somehow related to the cholinosensitive
structures responsible for yawning.
The effect of serotonin at this level seems to
be only positively modulatory, because no
yawning has been observed by the administration
of citalopram alone. This interpretation is
supported by the blocking effect of metergoline,
both on the yawning-potentiating effect of
citalopram and on the yawning-inducing effect of
physostigmine, metergoline being a quite
selective blocking agent of serotonin
receptors.
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