mystery of yawning
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La parakinésie brachiale oscitante
Yawning: its cycle, its role
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Fetal yawning assessed by 3D and 4D sonography
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Le bâillement, du réflexe à la pathologie
Le bâillement : de l'éthologie à la médecine clinique
Le bâillement : phylogenèse, éthologie, nosogénie
 Le bâillement : un comportement universel
La parakinésie brachiale oscitante
Yawning: its cycle, its role
Warum gähnen wir ?
 
Fetal yawning assessed by 3D and 4D sonography
Le bâillement foetal
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22 août 2011
Physiology & Behavior
1989;45:1263-1266
Yawning Induced by the Selective Dopamine D2 Agonist N-0437 is Blocked by the Selective Dopanrine Autoreceptor Antagonist (+)-UH 232
 
Cooper SJ, Rusk IN, Barber DJ

Chat-logomini

 
Yawning and stretching responses were elicited in rats by a small dose (0.3 mg/kg) of the highly selective dopamine D2 agonist. N-0437. The responses were blocked by the highly selective dopamine autoreceptor antagonist, (+)-UH 232 (3.0 mg/kg), but not by raclopride at a dose which selectively blocks postsynaptic D2 receptors. The results strongly confirm the view that yawning and stretching are behavioral responses elicited by stimulation of presynaptic D2 receptors
 
 
Small doses of dopamine agonists elicit a behavioral syndrome comprising yawning, forepaw-stretching, and penile grooming in male rats. It has been proposed that these effects are due to selective agonist activity at dopamine autoreceptors , although evidence against this view has also been put forward. One means to determine the mechanism by which dopamine agonists elicit yawning and the other responses would be to use selective dopamine autoreceptor antagonists to see if the response to the agonists could be blocked. Recently, dopamine receptor antagonists have been characterised in an extensive series of in vivo biochemical and behavioral experiments. Hence, in the present report, we examined the effectiveness of one dopamine autoreceptor antagonist, (+)-UH 232, in blocking the responses to a small dose of a selective dopamipe agonist.
 
The dopamine agonist chosen for this study is the highly specific dopamine D2 agonist, N-0437. In small doses, it has been reported to act preferentially at dopamine autoreceptors. We have observed that at 0.3 mg/kg IP, N-0437 induced hypomotility, which is indicative of autoreceptor activation, whilst at 1.0 and 3.0 mg/kg it produced mild forms of behavioral stereotypy (sniffing, oral activity) which denote postsynaptic receptor-mediated effects. Hence, our aim was to determine if N-0437 at 0.3 mg/kg also elicits yawning and associated responses, and then to test for antagonism with (+)-UH 232. As a control measure, raclopride, a highly-selective D2 receptor antagonist (8) was also tested at a dose which selectively blocks postsynaptic dopamine-mediated responses. This should have little or no effect on drug-elicited yawning.
 
Results
 
The highly selective D2 agonist, N-0437, elicited yawning at a small dose of 0.3 mg/kg. Individual differences were considerable, although in the first test there was a median value of 36 yawns in the 60 min period of observation. The maximum value was 76, and this rose slightly to 84 and 80 in subsequent tests. There were no significant differences for any time interval between the three N-0437 tests. The selective dopamine receptor antagonist, (+)-UH 232, significantly reduced the rate of yawning induced by N-0437 down to a baseline value, over the 60-min test. Its antagonistic effect was present within the first 20-min period. In contrast, raclopride (0.03 mg/kg) had no effect on N-0437induced yawning.
 
Stretching occurred at substantially lower rates than yawning. Nevertheless, a similiar pattern of drug effects emerged. N-0437 significantly increased the incidence of stretching; the effect was antagonized by (+)-UH 232, but not by raclopride.
 
At the doses used, neither dopamine antagonist induced either yawning or stretching (data not shown).
 
Discussion
 
Using a novel, selective dopamine autoreceptor antagonist, (+ )-UH 232, the present results provide strong confirmation of the view that yawning and stretching responses elicited by N-0437 are mediated by dopamine autoreceptors. Antagonism at postsynaptic dopamine D2 receptors had no effect on the elicited yawning and stretching responses.
 
Recently, N-0437 has been resolved into its enantiomeric forms. (- )N-0437 acts as an agonist at both pre- and postsynaptic dopamine receptors, while (+)N-0437 behaves as an antagonist at autoreceptors involved in the release of dopamine, and as a weak antagonist at postsynaptic dopamine receptors. In confirmation and extension of the present data, we have demonstrated that (- )N-0437 elicits yawning (peak effect, 36 yawns in 60 mm). whereas (+)N-0437 does not (Timmerrnan, Rusk. Horn and Cooper, submitted). The action of N-0437 to elicit yawning is therefore stereoselective, and requires agonis t activity at presynaptic autoreceptors involved in the control of dopamine release to induce the behavioral effect.
 
Although many investigators have proposed that small doses of dopamine agonïsts elicit yawning through a selective action at dopamine autoreceptors, there has been dissent from this view. Morelli et al. reported that the dopamine D1 antagonist, SCH 23390, antagonized yawning induced by apomorphine. They concluded that the locus of the antagonism may involve postsynaptically-situated dopamine D1 receptors. However, it should be noted that SCH 23390 also binds to 5-HT2 receptors in the brain. Since serotonergic mechanisms may have a facilitatory role with respect to apomorphine-induced yawning, the pharmacological significance of the report by Morelli et al. is somewhat unclear. Furthermore, Gower et al. were unable to elicit yawning responses with the selective dopamine D1 agonist, SK&F 38393. Our results, in contrast, firmly indicate that agonist activity at presynaptic dopamine D2 receptors is necessary to elicit yawning and stretching responses.
 
It is interesting to note that spontaneous yawning in the rat shows circadian variation. Yawning is most frequent in the late light and early dark period. This coincides with lowest turnover rates for dopamine in the rat brain. As the night period proceeds, dopamine release in nucleus accumbens and striatum increases dramatically , and, therefore, autoreceptor sensitivity would be expected to decline. As a result, behavioral responses mediated by dopamine autoreceptors should prove more difficult to obtain during the later parts of the dark period. Future experiments could examine relationships between the phase of the day-night cycle, and behavioral responsiveness to dopamine autoreceptor stimulation and antagonism.
 
Investigations into behavioral responses mediated by dopamine autoreceptors may have clinical relevance. Szechtman et al. have recently reported that a small dose of apomorphine induced yawning responses in men, and the drug effect showed sensitization with repeated injections. Since sensitization processes may be involved in the development and exacerbation of psychosis, Szechtman et al. suggest that further studies on yawning may provide a useful means to study dopaminergic mechanisms involved in schizophrenia. Using a selective dopamine autoreceptor antagonist, our data firmly link yawning responses to presynaptic dopamine receptor activation, and indicate that autoreceptor mechanisms deserve close experimental scrutiny in relation to neural processes underlying psychosis.
 
 
-Banks RJ, Mozley L, Dourish CT. The angiotensin converting enzyme inhibitors captopril and enalapril inhibit apomorphine-induced oral stereotypy in the rat. Neuroscience. 1994;58(4):799-805  
-Stoessl AJ, Dourish CT, Iversen SD Apomorphine-induced yawning in rats is abolished by bilateral 6-hydroxydopamine lesions of the substantia nigra Psychopharmacol; 1987; 93; 336-342
-Stoessl AJ Effects of ageing on the behavioural responses to dopamine agonists: decreased yawning and locomotion, but increased stereotypy Brain Research 1989; 495; 20-30
-Stoessl AJ, Dourish CT, Iversen SD The NK-3 tachykinin agonist senktide elicits yawning and chewing mouth movements following subcutaneous administration in the rat. Evidence for cholinergic mediation. Psychopharmacology (Berl). 1988; 95; 4; 502-506
-Cooper SJ; Dourish CT Neural basis of drug induced yawning in neurobiology of stereotyped behaviour Oxford ed 1990
-Cooper SJ, Rusk IN, Barber DJ. Yawning Induced by the Selective Dopamine D2 Agonist N-0437 is Blocked by the Selective Doparnine Autoreceptor Antagonist (+)-UH 232. Physiol Behav. 1989;45:1263-1266
-Dourish CT, SJ Cooper Yawning elicited by sytemic and intrastriatal injection of piribedil and apomorphine in the rat Pyschopharmacology 1985; 86; 175-181
-Dourish CT, PH Hutson Bilateral lesions of the striatum induced with 6-hydroxydopamine abolish apomorphine-induced yawning in rats Neuropharmacology 1985; 24; 11; 1051-1055
-Collins G, JM Witkin et al Dopamine agonist-induced yawning in rats: a dopamine d3 receptor mediated behavior J Pharmacol Exp Ther 2005
 
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