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mise à jour du 6 février 2003
Pharmacol Biochem Behav 1989; 32; 3; 815-8  
Potentiation by serotonergic inhibition of yawning induced by dopamine receptor agonists in rats
Matsumoto S, Yamada K, Nagashima M, Matsuo N, Shirakawa K, Furukawa
Department of Pharmacology, School of Medicine Fukuoka University, Japan


There is accumulated evidence that systemic administrations of low doses of dopamine receptor agonists, such as apomorphine, bromocriptine, piribedil and 3-PPP, elicit yawning in rats. The yawning behavior induced by dopamine receptor agonists is blocked by dopamine D2-receptor antagonists. On the basis of such findings, it has been proposed that dopamine D2-receptor stimulation participates in the occurrence of yawning.
B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo (4,5 d) azepine) has recently been characterized as a selective agonist at brain dopamine autoreceptors. B-HT 920 also induced yawning behavior without eliciting stereotyped behavior in rats. The present authors and Serra et al. have previously reported that apomorphine-induced yawning behavior is enhanced by treatment with reserpine which reduces levels of catecholamine and serotonin in the brain.
The present study was therefore performed to investigate whether catecholaminergic and/or serotonergic neuron activities are related to the enhancement by reserpine of yawning evoked by dopamine receptor agonists. [...]
Discussion :
The present experiment has confirmed that the mixed dopamine D1/D2 receptor agonists, apomorphine and piribedil induce yawning behavior in rats but the selective dopamine D1-receptor agonist SK&F 38393, is inactive. It is also observed that the dopamine autoreceptor agonist, B-HT 920, induced yawning behavior. The yawning produced by B-HT 920 was inhibited by the dopamine D2-receptor antagonist, spiperone at a dose of 0.5 mg/kg, or the muscarinic receptor antagonist, scopolamine at dose of 0.5 mg/kg, but was unaffected by the selective dopamine D1-receptor antagonist, SCH 23390 at a dose of 0.5 mgfkg.
The doses of these receptor antagonists were selected according to the other experiment in which the yawning elicited by apomorphine or piribedil was inhibited by spiperone and scopolamine, but not by SCH 23390, while that induced by physostigmine was inhibited by scopolamine, but not by spiperone and SCH 23390, at above-mentioned doses. At these doses, the antagonists did not induce motor debilitation. Therefore, these receptor antagonists at the doses used are producing their inhibitory effects on B-HT 920-induced yawning behavior in a pharmacologically relevant manner, and are not exerting their antagonistic actions through general motor debilitation. Thus, the antagonisms by the receptor antagonists for B-HT 920-induced yawning coincide with those for apomorphine-elicited yawning. Accordingly, it is now well acceptable that yawning involves dopamine D2receptor stimulation and consequent muscarinic activation.
Serra et al. reported that a significant increase in the number of yawns was observed in rats 24 hr, but not 1, 6 and 12 hr, after treatment with reserpine (5 mgikg, IP). This reserpine-induced yawning was antagonized by the dopamine D2receptor antagonist, sulpiride, and by the catecholamine synthesis inhibitor, alpha-MT, suggesting that this behavior may be induced by endogenously released dopamine.
The treatment with reserpine for 24 hr also potentiated the yawning induced by the dopamine D2-receptor agonist, (+)-3-PPP. From these results, they have proposed that yawning behavior is due te, the stimulation of a population of dopamine receptors having a high affinity for dopamine receptor agonists similar to that of dopamine autoreceptors but located postsynaptically. On the other hand, Longoni et al. observed that the yawning responses to dopamine D2receptor agonists, such as B-HT 920 and (+)-3-PPP, were reduced by 6 hr treatment with reserpine. The yawning induced by these dopamine receptor agonists was completely abolished by sulpiride and was also slightly but significantly reduced by SCH 23390. Thus, it was proposed that stimulation of D1-receptors by endogenously released dopamine plays a permissive-facilitatory role for the behavioral expression of dopamine D2-receptor activation. In the present experiments, the yawning responses to B-HT 920, apomorphine and piribedil were enhanced by 24 hr treatment with reserpine (5 mg/kg, IP). However, SK&F 38393 failed to induce yawning even after reserpine. Furthermore, the yawning elicited by B-HT 920 in combination with reserpine was markedly inhibited by spiperone or scopolamine, but was not significantly reduced by SCH 23390. Accordingly, although dopamine released endogenously is proposed to play at least in part a facilitatory role, the stimulation of dopamine D1-receptors may not be an essential factor in the occurrence of yawning.
Interestingly, the dopamine receptor agonist-induced yawning was also increased by the serotonin synthesis inhibitor, PCPA, but was not influenced by alpha-MT, implying that depletion of serotonin plays a more important role than that of catecholamines in potentiation of yawning. The yawning evoked by combined administration of B-HT 920 and PCPA was completely inhibited following spiperone or scopolamine.
Most recently, it was reported that apomorphine-elicited yawning was enhanced by pretreatment with PCPA or the serotonergic neurotoxin, 5,7dihydroxytryptamine, and was contrarily reduced by pretreatment with the serotonin precursor, 5-hydroxytryptophan. In fact, serotonin is present in relatively high concentrations in the rat striatum, where is proposed to be one of the sites of action of dopamine receptor agonists in the occurrence of yawning. Various lines of evidence have shown that the origin of serotonergic neurons in the striatum is the dorsal raphe, and that there are inhibitory serotonin receptors located on terminals of dopaminergic neurons in the striatum. Lesioning of the raphe nucleus which reduces serotonin levels in the forebrain has been reported to cause an increase of dopamine release. Therefore, treatment with PCPA may increase the release of dopamine, which is proposed to play a facilitatory role in the occurrence of yawning, though more work is clearly warranted to clarify the nature of the observed serotonergic-dopaminergic neuron interaction.
From the results, it is assumed that the occurrence of yawning following dopamine receptor agonists involves stimulation of dopamine D2-receptors having a high affinity and consequent muscarinic activation, and that the potentiation by reserpine or PCPA of yawning induced by dopamine receptor agonists is due to decreases in serotonergic neuron activity.
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