mise à jour du
1 septembre 2003
Br J Pharmacol
Inhibitory effect of morphine on yawning induced by cholinoceptor and dopamine D2 receptor activation in rats
Zarrindast MR and A Jamshidzadeh
Department of pharmacology, school of medecine
Teheran University of medical sciences
Teheran Iran
Index de tous les travaux de MR Zarrindast


Introduction : Yawning is a physiological response which is associated with fatigue and recovery from stress. A number of dopamine agonists including apomorphine and bromocriptine elicited yawning behaviour in rats. It has been proposed that this behaviour is mediated via a D2 dopamine autoreceptor.
Central cholinoceptor activation by physostigmine or pilocarpine also induces yawning. The yawning induced by dopamine agonists and agents acting on cholinoceptors are inhibited by muscarinic antagonists, such as scopolamine and atropine. These studies suggest that dopamine receptor agonists induce yawning by activation of the cholinergic system. Links between acetylcholine and dopaminergic neurones have been described in the septohippocampal system and the striatum and it has been shown that stimulation and lesion of these structures affect yawning. It has also been suggested that dopamine agonists elicit yawning by stimulating dopamine D2 receptors within these structures.
Opiate interactions with both dopaminergic and cholinergic systems have been demonstrated. There appears to be a close association between opiate receptors and dopaminergic cell bodies and nerve endings in the substantia nigra and striatum. Morphine, methadone and other opiates modulate dopaminergic neurotransmission in mesolimbic and nigrostriatal projections. Opiate agonists also inhibit the release of acetylcholine in the central nervous system, an effect which is antagonized by naloxone.
In the present study, we have evaluated the effect of morphine on yawning induced by dopaminergic and cholinergic activation. [...]
Discussion :It has been proposed that yawning induced by low doses of dopamine receptor a gonists is due to activation of D2 receptors, although D1 receptors may be involved in yawning induced by apomorphine. The yawning induced by dopamine agonists appears to be mediated via a cholinergic mechanism, since it is inhibited by muscarinic receptor blockade
Although dopaminergic and cholinergic interactions have been described at various anatomical sites within the brain, the locus of the interaction with respect to yawning behaviour has not been established, although it has been démonstrated that intact nigrostriatal projections are required for drugs acting on dopamine receptors to induce yawning. In the present study bromocryptine induced yawning was inhibited in a naloxonesensitive manner by morphine. Although the nigro-striatal pathway has been shown to be regulated by µ and opioid receptors in both the striatum and the substantia nigra, such a mechanism is unlikely to explain the present results since morphine in a similar dose range also inhibited cholinoceptor-mediated yawning.
Although morphine is able to inhibit the release of acetyl choline in the central nervous system in a naloxone-sensitive manner such a mechanisrn is unlikely to explain the present results since morphine was able to inhibit the yawning induced by the direct acting cholinoceptor agonist, as weil as that induced by physostiginine.
We have previously demonstrated that yawning induced by bromocriptine and physostigmine are decreased by theophyl- line (Zârrindast & Poursoltan, l989). Theophylline is an adenosine receptor antagonist and a phosphodiesterase inhibitor which increases intracellular adenosine 3',5'-cyclic monophosphate (cyclic AMP) concentrations, and may also release dopamine. However, a similar mechanism is unlikely to explain the present effects since morphine bas been reported to stimulate adenosine release.
The most likely explanation of the present findings is that morphine inhibits yawning induced by dopamine agonists and drugs acting at cholinoceptors at an opioid site downstrearn from both the dopamine receptors- and cholinoceptors. The weak but dose-dependent induction of yawning by naloxone suggests that endogenous opioids may mediate a tonic inhibitory effect on yawning behaviour.
-Melis MR et al. Prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning: involvement of nitric oxide Naunyn-Schmiedeberg's arch Pharmacol 1997; 600; 355-595
-Zarrindast MR, Poursoltan M Interactions of drugs acting on central dopamine receptors and cholinoceptors on yawning responses in the rat induced by apomorphine, bromocriptine or physostigmine Br J Pharmacol 1989; 96; 4; 843-848
-Zarrindast, MR, Jamshidzadeh A Inhibitory effect of morphine on yawning induced by cholinoceptor and dopamine D2 receptor activation in rats Br J Pharmacol 1992; 105; 3; 675-8
-Zarrindast MR, Toloui V, Hashemi B Effects of GABAergic drugs on physostigmine-induced yawning in rats; Psychopharmacology (Berl) 1995; 122; ; :297-300
-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
-Philibert C, Sauveplane K, Pinzani-Harter V et al. Le bâillement: de la physiologie à la iatrogénie. La lettre du pneumologue. 2011;14(5):168-172