Introduction : Yawning behavior
elicited by low doses of apomorphine is
attributed to stimulation of the inhibitory
presynaptic dopamine (DA) autoreceptors.
Physostigmine also elicits yawning. Apomorphine
elicited yawning can be reduced by pretreatment
with the muscarinic antagonist scopolamine while
physostigmine elicited yawning can be enhanced
by pretreatment with the neuroleptics spiperone
spiroperidol, haloperidol and fluphenazine. It
has been proposed that dopaminergic and
cholinergic related factors may interact to,
elicit yawning behavior. Moreover, a
dopaminergic-cholinergic link is recognized in
the striatum. DA receptors are localized on the
striatal acetylcholine (ACh) neurons and an
inhibitory dopaminergic input may influence the
cholinergic system of the striatum.
Electrophysiological evidence confirmed that the
nigrostriatal dopaminergic neurons inhibit the
striatal and cholinergi neurons.
Serotonin (5-HT) is also present in
relatively high concentrations in the striatum
of the rat. The origin of 5HT fibres in the
striatum is the dorsal raphe. Evidence obtained
from electrophysiological studies showed that
5-HT acts as an inhibitory transmitter. Olpe and
Koella (1977) have shown that stimulation of the
dorsal raphe neurons has a potent inhibitory
action on striatal neurons. Davis and Tongroach
(1978) demonstrated that the inhibition of
striatal neuronal firing produced by stimulation
of the dorsal raphe nucleus could be mimicked by
the iontophoretic application of 5-HT in the
striatum and that both effects were antagonized
by methysergide, a drug which blocks the
postsynaptic 5-HT receptors. Similarly,
biochemical studies indicated that there are
inhibitory 5-HT receptors located on terminals
of dopaminergic neurons in the striatum.
Therefore, yawning elicited by apomorphine
and/or physostigmine is probably affected by
changes in serotonergic neuronal activities.
However, yawning behavior and serotonergic
functions have not been extensively studied. In
the present study, the possible influence of
5-HT on druginduced yawning in rats was
investigated.
Discussion : Apomorphine and
physostigmine cause yawning in rats, in a
biphasic manner, ie., low, but not high, doses
produce yawning behavior. The peak effects of
apomorphine and physostigmine were observed with
a dose of 0.1 mg/kg, s.c. of each drug. This
observation was in good accord with the data in
the literature.
Apomorphine elicited yawning was reduced
following pretreatment with the 5-HT precursor,
5-HTP, but was enhanced by pretreatment with the
5-HT synthesis inhibitor p-CPA or the
serotonergic neurotoxin 5,7-DHT. These findings
indicate that apomorphine elicited yawning is
enhanced by decreases in serotonergic-related
neuronal activity and reduced by increases in
such neuronal activity.
Ennis et al. (1981) reported that inhibitory
5-HT receptors are reported on the terminals of
the dopaminergic neuron in the located. DA
release is inhibited not only by DA but also, by
5-HT in striatal slices. In addition, the
excitatory behavior noted when DA receptors are
stimulated can be mimicked or enhanced by p-CPA
pretreatment, 5,7-DHT pretreatment, raphe
nucleus lesion and attenuation of 5-HT receptor
stimulation. Likewise, lesioning of the
raphe which reduces 5-HT levels in the
forebrain causes a significant increase in the
concentration of 3,4-dihydroxyphenylacetic acid
(DOPAC). Thus, the inhibitory effects of 5-HT
seem to be mediated via 5-HT receptors at the DA
nerve terminals. Actually, apomorphine enhanced
WDS induced by 5-HTP. WDS induced by 5-HTP may
involve the activation of serotonergic neuron
activity. Apomorphine, in a low dose, elicited
only yawning in control rats, whereas the same
dose elicited stereotypy in rats pretreated with
higher doses of p-CPA.
Marini (1981) reported that serotonergic
activation and dopaminergic inhibition can act
concomitantly in the expression of drug-elicited
yawning in cats. Unlike the findings in cats,
potent serotomimetic drugs (LSD-like
hallucinogens) do not appear to elicit yawning
in rats, These observations suggested that the
behavioral pharmacology of yawning differs
between these species. In the present
experiments, 5-HTP pretreated rats never showed
yawning behavior.
Physostigmine-elicited yawning was reduced
by pretreatment with 5-HTP. However,
physostigmine-elicited yawning was not affected
by pretreatment with p-CPA and 5,7-DHT. These
observations are difficult to reconcile with
those of Urba-Holmgren et al. (1978) who found
that yawning induced by physostigmine was
enhanced by Lu 10-171, a selective 5-HT uptake
inhibitor, which, by itself does not induce
yawning. This effect was counteracted by
metergoline which blocks 5-HT postsynaptic
receptors. Although we have not precise
explanation for this difference, experimental
conditions and the age of the rats may play some
role.
Microinjecting apomorphine directly into,
the striatum elicited yawning behavior, with a
bell-shaped dose response curve. Stereotypy was
also observed when the highest dose of
apomorphine was given. Intrastriatal
microinjection of physostiginine had no effect
on behavior. These findings indicate that the
site of action of apomorphine differs from that
of physostigmine. Dourish et al. (1985)
suggested that a cholinergic-dopaminergig linked
system in the striatum was involved in the
induction of yawning. However, our results did
not support this hypothesis because (i)
physostigrnine elicited yawning was not affected
by pretreatinent with p-CPA and 5,7-DHT, (ii)
direct microinjection of physostigmine into the
striatum did not elicit yawning.
