I Ushijima, K Yamada, T Inoue, T Tokunaga, T
Furukawa
Department of Pharmacology,
School of Medicine, Fukuoka University,
Japa
It is known that a characteristic
stretching-yawning syndrome appears after
intracerebral injection of
a-melanocyte-stimulating hormone (a-MSH) or a
chemically related peptide, adrenocorticotrophic
hormone (ACTH) in many animals. The
stretching-yawning syndrome elicited by a-MSH or
ACTH is inhibited by the treatment with
cholinergic and dopaminergic antagonists,
suggesting a possible involvement of
cholinergiec and dopaminergic neurons. Moreover,
Wood et al. have
proposed that the septal-hippocampal cholinergic
neurons are necessary to elicit a specific
stretching-yawning syndrome following a-MSH or
ACTH since intraventricular injection of a-MSH
or ACTH increases the turnover rate of
acetylcholine in the hippocampus of rats.
On the other hand, cholinergic agonists have
also been reported to induce yawning in infant
and adult rats. Our
previous results show that intraperitoneal
injections of apomorphine at low doses, which
inhibit dopamine release from presynaptic sites,
induced yawning in adult rats and a
dopaminergic-cholinergic neuron link was
involved in yawning behavior.
In the present experiments, we noticed
yawning accompanied by a marked protrusion of
the tongue or teeth chattering following
physostigmine and pilocarpine, and investigated
influences of muscarinic and nicotinic
cholinergic agents on these symptoms.
Furthermore, we studied effects of haloperidol
at a low dose on yawning behavior.
[...]
DISCUSSION
Physostigmine, an anticholinerase agent, and
pilocarpine, a cholinergic agonist predominantly
acting upon muscarinic receptors, elicited
yawning with a marked tongue protruding or teeth
chattering. The yawning was blocked by
scopolamine, which blocks muscarinic cholinergic
receptors, but not by methylscopolamine, a
peripheral anticholinergic agent. Moreover, the
yawning induced by the cholinergic agonists was
not inhibited by mecamylamine, a nicotinic
receptor blocking agent, supporting a previous
report that nicotine did not induce yawning.
Considered together, these results confirm
that yawning behavior is essentially mediated
through the stimulation of central muscarinic
receptors but not nicotinic receptors.
Tongue protruding was also observed after
the treatment with physostigmine which increases
the concentrations of endogenous acetylcholine
in the synaptic clefts. Mecamylamine did not
inhibit yawning but selectively blocked the
tongue protruding. The tongue protruding, as
well as yawning, was also inhibited by
scopolamine but this inhibition may be resulting
from the decrease of yawning. Moreover, a
muscarinic receptor agonist, pilocarpine, failed
to evoke tongue protruding. Accordingly, it is
likely that physostigmine-induced tongue
protruding may involve, in part, an activation
of nicotinic receptors.
Recently, Dubuc
et al. have reported that
physostigmine-induced yawning was unaffected by
neuroleptics such as haloperidol, mezilamine and
sulpiride but inhibited by clozapine and
thioridazine, which have antimuscarinic actions
in addition to a dopamine receptor blocking
action. In the present experiments, low doses of
haloperidol, which have been reported to block
presynaptic dopamine receptors, failed to affect
the yawning elicited by physostigmine and
pilocarpine. On the other hand, yawning was also
elicited by low doses of apomorphine, which have
been reported to stimulate presynaptic dopamine
autoreceptors, and consequently inhibit dopamine
release.
This apomorphine-induced yawning was blocked
by scopolamine and a low dose (0.02 mglkg) of
haloperidol, these results being compatible with
reported data that apomorphine-induced yawning
was blocked by doses of haloperidol well below
those inhibiting the stereotypy evoked by
apomorphine. Considered together, these
experimental findings lend additional support to
the hypothesis that an activation of cholinergic
neurons resulting from an inhibition of dopamine
release from presynaptic sites in the
dopaminergic-cholinergic neuron link is involved
in apomorphine-induced yawning.
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