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26 février 2004
Bilateral lesions of the striatum induced with 6-hydroxydopamine abolish apomorphine-induced yawning in rats
CT Dourish, PH Hutson
Department of Neurochemistry, Institute of Neurology, The National Hospital, London

Considerable interest has developed in a syndrome of yawning and sexual arousal which is produced by small doses of dopamine agonists in rats. The yawning syndrome is thought to be the consequence of an inhibition of dopaminergic transmission in the brain mediated by the stimulation of dopamine autoreceptors.
Thus, doses of dopamine agonists which produce yawning, after systemic injection, are within the range thought to activate autoreceptors, but smaller than doses required to, produce signs of stimulation of postsynaptic dopamine receptors, such as hyperactivity and stereotypy. In addition, novel drugs, which are claimed to be selective dopamine autoreceptor agonists produce yawning in rats. Yawning induced by dopamine agonists appears to be centrally mediated since the response is elicited by microinjection of piribedil and apomorphine into dopamine-containing terminal regions of the forebrain. Furthermore, yawning induced by apomorphine is abolished by the centrally-acting dopamine antagonist haloperidol, but unaffected by the peripheral dopamine antagonist domperidone.
In the present study, evidence is provided that apomorphine-induced yawning and chewing is depenilent on the integrity of the dopaminergic innervation of the striatum, since the response to, a small dose of apomorphine, given systemically, was abolished by bilateral lesions of the striatum induced with 6-hydroxydopamine (6-OHDA). [...]
The present data confirm many previous findings that a small dose of apomorphine produces a syndrome of yawning and sexual arousal in male rats. Most previous authors have suggested that yawning induced by dopamine agonists is mediated by presynaptic dopamine autoreceptors.
In the present study, the yawning syndrome (i.e. yawning, chewing, penile grooming) was abolished by a 58% depletion of striatal dopamine, produced by bilateral lesions of the striatum, induced by 6-OHDA. These data are consistent with the mediation of yawning by presynaptic dopamine receptors since it is well established that postsynaptic dopamine receptors become supersensitive to direct dopamine agonists after dopaminergic denervation. For example, rats with lesions of the striatum and nucleus accumbens induced with 6-OHDA show enhanced locomotor stimulation and stereotypy (ie. sniffing, head movements, gnawing) in response to apomorphine, compared to intact animals.
Indeed, in the present study, there was limited evidence for the development of supersensitivity of postsynaptic dopamine receptors since a number of rats lesioned with 6-OHDA were observed to exhibit increased sniffing in response to 0.1 mg/kg of apomorphine. In contrast, increased sniffing was never observed in intact animals or sham controls after this drug dose (N.B. 0.2-0.5 mg/kg apomorphine is reported to be the threshold dose to elicit sniffing in rats. However, it should be noted that the possibility of mediation of yawning by postsynaptic dopamine receptors cannot be completely ruled out at present. Apomorphine-induced yawning exhibits a bell-shaped dose-response curve and yawning is generally produced by 0.025-0.2 mg/kg of the drug. In the present study only one dose of apomorphine (0. 1 mg/kg) was tested and therefore it is possible that the lesions induced with 6-OHDA may have produced a shift to the left in the dose-response curve which could have caused the disappearance of yawning at the dose of 0.1 mg/kg.
The data indicate that dopaminergic innervation of the striatum plays an important role in the mediation of yawning induced by dopamine agonists. This is consistent with the observation that microinjection of piribedil and apomorphine into the striatum elicits an identical syndrome of yawning, chewing and sexual arousal.
Previous studies have reported that sexual arousal (i.e. penile grooming, erection and ejaculation) and occasional stretching are associated with yawning induced by dopamine agonists in male rats. However, only one previous study has reported that chewing mouth movements are associated with yawning. The prescrit findings are in agreement with the latter study and show that chewing generally precedes and succeeds yawning induced by systemie or intrastriatal injection of dopamine agonists. Furthermore, the present study showed that depletion of dopamine in the striatum abolished not only yawning induced by apomorphine but also sexual arousal and chewing. Therefore, chewing jaw movements may be an integral part of the yawning syndrome, induced by dopamine agonists, in male rats.
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