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26 décembre 2002
Arch Int Pharmacodyn 1985;273:196-201
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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