Dopamine agonist-induced yawning in rats: a dopamine D3 receptor mediated behavior
Collins G et al

mise à jour du
25 juillet 2002
 Pharmacol Biochem Behav
1999; 62; 1; 1-5
 Influence of different adrenoceptor agonists and antagonists on physostigmine-induced yawning in rats
Zarrindast MR, Fazli-Tabai S, Semnanian S, Fathollahi Y
Department of pharmacology, school of medecine
Teheran University of medical sciences
Teheran Iran
A trial of subcutaneously injected apomorphine for parkinsonian
Index de tous les travaux de MR Zarrindast
Yawning behavior is a curious and still little-understood phenomenon that is displayed in many vertebrate species. Despite the great sociobiological importance and extraordinarily widespread incidence of yawning, this stereotyped behavior bas been the subject of very little empirical research. The behavior, if practiced in excess, may be a sign of diseases such as chorea, brain tumors, or encephalitis.

Most rats normally show one to two episodes of yawning per hour. They are usually sleepy during the time of yawning, but yawning can be elicited in experimental animals by the cholinergic agents physostigmine and pilocarpine, which is inhibited by muscarinic blockade. Considerable interest bas developed in a yawning syndrome that is produced by dopamine agonists in rats. The paraventricular nucleus, incerto-hypothalamic dopamine system, and septal and striatal dopamine receptors have A been suggested to mediate yawning in rats. The behavior scems to be mediated through D2 dopamine receptors. Central cholinergic mechanisms mediate the yawning induced by dopamine receptor agonists, and the response is inhibited by muscarir& antagonists such as scopolamine and atropine.

The influences of GABAergic agents, adenosine receptor agents and opioidergic agents on cholinergicinduced yawning have been investigated in our previous work. There is evidence that the adrenceptor system may influence some behaviors in rats. In the present study, effects of adrenoceptor mechanism(s) on physostigmine-induced yawning were studied. [...]


In this work, the influence of adrenoceptor agonists and antagonists on physostigmine-induced yawning were investigated. Previous studies have shown that cholinergie or dopamine D2 receptor activation induce yawning. The behavior induced by cholinoceptor agents is antagonized by muscarinic receptor antagonists but not by dopaminergic receptor antagonists, and behavior induced by dopamine D, receptor agonists is inhibited by both dopaminergic and muscarmie receptor antagonists. These data imply that the yawning induced by cholinoceptor agents involves activation of cholinergic neuronal mechanism(s), and the yawning induced by dopaminergic receptor agonists appears to be mediated via activation of dopaminergic and cholinergic mechanisms. The yawning can also be influenced by different systems (e.g., dopaminc D1 receptor stimulation; opiodergic, GABAergic and adenosine mechanisms). Together with evidence for the role of dopaminergic, cholinergic, and other mechanisms in mediating yawning, evidence also indicates an important modulatory role for the noradrenergic system.

The present results show that intraperitoneal (IP) injection of the cholinesterase inhibitor, physostigmine, induced dosedependent yawning. The response was maximal with 0.2 mg/ kg of the drug. This is in agreement with previous work that found that activation of the cholinergic mechanism may induce yawning. The present data indicate that administration of the alpha2-adrenoceptor agonist. phenylephrine, and the alpha2-adrenoceptor agonist, clonidine, decreased physostigmine's effect. Therefore, it can be suggested that adrenergic system(s) is involved in the present response. This may be in agreement with other reports that indicate that adrenoceptor mechanisms may influence some of the behaviors in rats. The effect induced by phenylephrine can be decreased by the alpha1-adrenoceptor antagonist, prazosin, which may show that inhibition of the yawning induced by phenylephrine is mediated through an alpha1-adrenoceptor mechanism. This is not consistent with data obtained by some authors who showed that physostigmine-induced yawning could not be affected by alpha1-adrenoceptors. The higher dose of the alpha2-adrenoceptor antagonist, yohimbine, also reduced the inhibition induced by clonidine. The possibility may exist that clonidine produces its effect through alpha2-receptor activity. This is in agreement with results obtained by some investigators who showed clonidine could reduce cholinergic-induced yawning. Because low doses of yohimbine by itself reduced physostigmine-induced yawning, receptor blockade by the alpha2-receptor antagonist cannot be shown. Thus, low doses of yohimbine may block et, presynaptic adrenoceptors and, in turn, may release noradrenaline. The released neurotransmitter may cause inhibition of physostigmine's response through activation of adrenoceptors. However, prazosin administration could not reduce the yohimbine influence on physostigmine-induced yawning.

Evidence also exists that alpha2-adrenoceptor activation may decrease dopamine release. Therefore, there may be a possibility that blockade alpha2-adrenoceptor by yohimbine releases dopamine. Stimulation of D1 dopamine receptors has also been shown to reduce yawning. Thus, the released dopamine may inhibit yawning through D1 receptor activation.

Overall, whether the activation of adrenergic system inhibited the release of acetylcholine or directly interacted with cholinergic mechanisrns involved in yawning it is not presently clear, and should be examined further. Prazosin, phenoxybenzamine, and propranolol by themselves did not change physostigmine-induced yawning. Therefore, the negative influence of the brain adrenergic mechanism(s) on the yawning behavior seems unlikely. However, il has been proposed that beta-adrenoceptor antagonists are able to increase yawning induced by cholinergie and doparninergic drugs.

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-Zarrindast MR, Fazli-Tabai S, Semnanian S, Fathollahi Y Influence of different adrenoceptor agonists and antagonists on physostigmine-induced yawning in rats. Pharmacol Biochem Behav 1999; 62; 1; 1-5