mise à jour du
15 juillet 2004
Pharmacol Biochem Behavior
Muscarinic and nicotinic effects on yawning
and tongue protruding in the rat
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. [...]
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.
-Fugikawa M; Yamada K; Nagashima M; Furukawa T Involvement of beta-adrenoreceptors in regulation of the yawning induced by neuropeptides; oxytocin and alpha-melanocytes stimuling hormone in rats. Pharmacol Biochem Behav 1995; 50; 339-343
-Furukawa T Yawning behavior for preclinical drug evaluation Meth Find Exp Clin Phamacol 1996; 18; 2; 141-155
-Kimura H; Yamada K; Nagashima M; Matsumoto S Role of adrenergic neuronal activity in the yawning induced by tacrine and NIK-247 in rats.Pharmacol Biochem Behav 1992; 43; 4; 985-91
-Kimura H; Yamada K; Nagashima M; Furukawa T Involvement of catecholamine receptor activities in modulating the incidence of yawning in rats.Pharmacol Biochem Behav 1996; 53(; 4; 1017-21
Ogura H, Kosasa T, Kuriya Y, Yamanishi Y Central and peripheral activity of cholinesterase inhibitors as revealed by yawning and fasciculation in rats. Eur J Pharmacol. 2001; 415; 2-3; 157-64
-Matsumoto S, Yamada K, Nagashima M, Matsuo N, Shirakawa K, Furukawa T Potentiation by serotonergic inhibition of yawning induced by dopamine receptor agonists in rats.Pharmacol Biochem Behav 1989; 32; 3; 815-8
-Serra G , Collu M and Gessa GL Yawning is elicited by D2 dopamine agonists but is blocked by D1 antagonist Psychopharmacology 1987; 91; 330-337
-Serra G, Gessa GL Hypophysectomy prevents yawning and penile erection but not hypomotility induced by apomorphine Pharmacology Biochemistry & Behavior 1983; 19; 917-919
-Serra G et al Cycloheximide prevents apomporphine induced yawning, penile erection and genital grooming in rats European Journal of Pharmacology1983; 86; 279-282
-Kostrzewa RM and R Brus Is dopamine-agonist induced yawning behavior a D3 mediated event? Life Sci 1991; 48; 26; 129
-Ushijima I, Mizuki Y, Yamada M Multifocal sites of action involved in dopaminergic-cholinergic neuronal interactions in yawning Psychopharmacology (Berl) 1988; 95; 34-7
-Ushijima I et al, Muscarinic and nicotinic effects on yawning and tongue protruding in the rat Pharmacol Biochem Behavior 1984; 21; 297-300
-Ushijima et al modification of apomorphine, physiostigmine and pilocarpine induced yawning after long term treatment with neuroleptic or cholinergic agents Arch Int Pharmacodyn 1984; 271; 180-188
-Ushijima I et al Characteristics of yawning behavior induced by apomorphine, physostigmine and pilocarpine Arch Int Pharmacodyn 1985; 273; 196-201
-Ushijima, I., Y. Mizuki, et al. Behavioral effects of dilazep on cholinergic, dopaminergic, and purinergic systems in the rat. Pharmacol Biochem Behav 1992;43(3): 673-676.
-Ushijima I, Mizuki Y, et al Effects of age on behavioral responses to dopamine agonists in the rat. Eur J Pharmacol. 1987;138(1):101-106.
-Ushijima I, Mizuki Y, Yamada M. The mode of action of bromocriptine following pretreatment with reserpine and alpha-methyl-p-tyrosine in rats. Psychopharmacology (Berl). 1988;95(1):29-33.
-Yamada K, Furukawa T Direct evidence for involvement of dopaminergic inhibition and cholinergic activation in yawning Psychopharmacology 1980; 67; 39-43
-Yamada K, Furukawa T The yawning elicited by alpha-melanocyte-stimulating hormone involves serotonergic -dopaminergic - cholinergic neuron link in rats Naunyn-Schmiedeberg's Arch Pharmacol 1981; 316; 155 -160
-Yamada K et al Involvement of septal and striatal dopamine D2 receptors in yawning behavior in rats Psychopharmacology 1986; 90; 9-13
-Yamada K et al Possible involvement of differing classes of dopamine d2 receptors in yawning and stereotypy in rats Psychopharmacology 1990; 100; 141-144
-Yamada K, Furukawa T Behavioral studies on central dopaminergic neurons. especially jumping, stretching, body shaking and yawning behavior J PharmacoBio dynamics 1980; 3; S16-S18
-Yamada K, Matsumoto S, Nagashima M, Kumagai M, Matsuo N, Furukawa T Stimulatory effects of beta-adrenoceptor blockers on the yawning induced by dopaminergic and cholinergic agonists in rats. Japanese J Pharmacology 1987; 43; supp53p
-Yamada K, S Matsumoto, M Nagashima, K Shirakawa, T Furukawa Potentiation of yawning responses to the dopamine receptor agonists B-HT 920 and SND 919 by pindolol in the rat J Neural Transm [GenSect] 1990; 79; 19-24