Characteristics
of yawning behavior induced by apomorphine,
physostigmine and pilocarpine
Itsuko Ushijima, Yasushi Mizuki, Michio
Yamada, T Furukawa
Department of
Neuropsychiatry, Yamaguchi University, School of
Medicine,
Ube, Japan
Introduction : Cholinomimetic drugs and low
doses of apomorphine have been reported to
induce yawning in infant and adult rats. The
yawning induced by apomorphine, physostigmine or
pilocarpine is inhibited by scopolamine, a
muscarinic receptor blocking agent, but not by
methyl scopolamine, a peripheral anticholinergic
agent or by mecamylamine, a nicotinic receptor
blocking agent. These findings suggest a
possible involvement of stimulation of the
central "muscarinic" receptor but not of the
central nicotinic receptor in mediating yawning
behavior.
It seems, however, that the neuronal
mechanisms involved in the various drug-induced
yawning behaviors are different. In the present
study, we found that the features of yawning
behaviors induced by various agents are
different and we attempted to further clarify
the possible neuronal mechanisms involved in
these characteristic behaviors.
Discussion :
Apomorphine-, physostigmine- and
pilocarpine-induced yawning was most prominent
at doses of 0.25 mg/kg, 0.2 mg/kg and 4 mg/kg,
respectively, as has been previously
reported.
Apomorphine, however, only induces yawning
at low doses which preferentially activate
presynaptic dopamine autoreceptors and only
stereotypy at high doses which stimulate
postsynaptic dopamine receptors. At low doses,
physostigmine and pilocarpine produced only
yawning but at higher doses, these agents induce
both chattering and yawning. The chattering as
well as the yawning appear to involve central
cholinergic activation because of inhibition by
scopolamine.
With regard to possible neuronal mechanisms
involved in yawning, it is likely that
apomorphine differs from physostigmine and
pilocarpine but both physostigmine and
pilocarpine appear to involve similar
mechanisms. In this study, however, the yawning
induced by physostigmine was similar to that
induced by apomorphine in terras of behavioral
features, with the exception of upward head
movement. It was dissimilar to that induced by
pilocarpine, since physostigmine elicited upward
yawning with wide and slow opening of the mouth
and with protrusion of the tongue, whereas
pilocarpine produced forward yawning with nallow
and brief opening of the mouth without tongue
protrusion and with higher frequency. The
features of physostigmine-induced yawning were
similar to those of natural yawning induced by
saline.
Pilocarpine directly stimulates cholinergic
receptors, whereas physostigmine inhibits
acetylcholinesterase and thereby increases
endogenous acetylcholine in the synaptic clefts.
It is well-known that acetylcholine stimulates
both muscarinic and nicotinic receptors while
pilocarpine stimulates mainly muscarinic
receptors. Mecamylamine, a nicotinic antagonist,
inhibits tongue protrusion induced by
physostigmine. In this study, mecamylamine also
inhibited tongue protrusion induced by
apomorphine and physostigmine, and shortened the
duration of yawning elicited by both drugs
without affecting yawning frequency.
Pilocarpine-induced yawning was not affected by
mecamylamine. It is tempting to speculate that
tongue protrusion may involve, in part,
activation of nicotinic receptors. Accordingly,
from the finding that the behavioral posture of
physiological yawning was similar to that of
physostigmineinduced yawning, it appears that
the physiological yawning may be mediated by
endogenous acetylcholine which activates both
muscarinic and nicotinic neurons.
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