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mise à jour du
13 novembre 2005
Prog Neuro-Psychopharmacol
& Biol Psychiat
1984; 8; 743-746
Timing of yawns induced by a small dose of
apomorphine and its alteration by naloxone
Henry Szechtman
Department of Neurosciences, McMaster University Hamilton, Ontario, Canada


1. The report examines the temporal sequence of yawns induced by apomorphine and whether the opiate antagonist, naloxone, affects it.
2. Before administering apomorphine (0.075 mg/kg) or saline, rats (n8) were pretreated with naloxone (1 mg/kg) or saline. Each subject received all 4 possible treatmants (saline-saline, saline-apomorphine, naloxone-saline, and naloxone-apomorphine) in random order.
3. Results indicate that yawning induced by apomorphine seems to come in fits; that is, there is a series of yawns spaced closely together and followed by a period of quiescence before the start of another cluster of yawns.
4. Naloxone reduced the number of apomorphine-induced yawns, and the occurrence of very short inter-yawn intervals.
5. It is suggested that the timing of yawns tray provide useful information regarding some pathologies and that opiates may potentiate the action of dopaminergic systems.
During the course of a study on the interaction of dopaminergic and opiate systems (Szechtman, submitted), I observed that after an injection of apomorphine, yawning in rats appears to come in clusters; that is, a series of yawns with short inter-yawn intervals, a period of quiescence, and then another fit of yawns. While the induction of yawning by low doses of apomorphine is well known (Dubuc et al., 1982; Holmgren and Urba-Holmgren, 1980; Lal et al., 1979; Mogilnicka and Klirnek, 1977; Nickolson and Berendsen, 1980; Serra et al., 1983; Yamada and Furukawa, 1980), the temporal characteristics of this response have not been documented. The purpose of this preliminary report is to draw attention to the seemingly non-random nature of the timing of yawns. In addition to apomorphine-induced yawning, data are presented showing that pretreatnent with naloxone alters their timing, reducing the occurrence of very short inter-yawn intervals.
There is a popular saying that "one yawn brings seven". Indeed, although he did not provide any data, Barbizet (1958) wrote that in humans "...a yawn is rarely isolated. It usually occurs in fits of two or three. The intensity of the yawn often increases, and each yawn is separated by a few regular breaths. Sometimes, the yawn will be repeated, irregularly, during several minutes." This report provides empirical support for this statement by shading that in rats after an injection of apomorphine, yawns seem to come in clusters. Furthermore, pretreatment with naloxone seems to alter the timing of yawns within a cluster, especially the occurrence of very short inter-yawn intervals. Because yawning is often associated with certain pathologies (reviewed by Barbizet, 1958; Heusner, 1946; Lehmann, 1979), the alteration in timing of yawns may prove useful as a differential indicator of sone of these disease states.
The fact that yawns come in fits suggests elements of positive feedback in the circuits mediating this response. The finding that the opiate antagonist, naloxone, reduces the very short inter-yawn intervals, suggests that endogenous opiates may he released during apomorphine-induced yawning and potentiate the action of dopaminergic system in this response. 1975) and emesis in dogs, would support the concept that lisuride has mainly central DA-activity, as suggested by Horowski and Wachtel (1976).
PE elicited by lisuride in rats was antagonized by both DA and 5-HT antagonists, rendering a simple interpretation difficult.
The antagonism might be non-specific and not exerted at the same receptor site, especially given the above mentioned, mild activation of PE by lisuride, in comparison with that obtained with other typical dopaminomimetics. On the other hand, the supposed dopaminergic nature of SY was confirmed by the clear antagonism obtained with haloperidol and sulpiride and by the failure of methysergide. Haloperidol, classically considered a dopamine antagonist drug, exerts its activity on pre- and post-synaptic DA-receptors (Long et al. 1975; Lokhandwala and Buckley 1977). Sulpiride seems also to be a specific DA-receptor antagonist with particular affinity for presynaptically located DA-receptors involved in the inhibition of DA-synthesis and release, the so-called autoinhibitor-receptors (Kehr et al. 1972; Carlsson 1975; Bunney and Aghajanian 1975; Di Chiara et al. 1976; Corsini et al. 1979; Spano et al. 1979).
Although detailed studies must obviously be undertaken on the biochemical changes in neurotransmission correlated with SY, our data suggest that this behavior might be an expression of a preferential DAautoreceptor-stimulation. It must be stressed that we observed that the low doses of lisuride which elicitSYsimultaneously induced sedation (that is, a considerable reduction in spontaneous locomotor activity-data not reported). This is in agreement with the behavioral effects of low doses of typical DA-stimulants such as APO and N PA, which elicit SY (Benassi-Benelli and Ferrari 1979; Benassi-Benelli et al. 1979) and sedation both in animals and in man (Di Chiara et al. 1976; Corsini et al. 1977a, b; Spano et al. 1979), simultaneously inhibiting dopaminergic firing and DA-synthesis in the caudate nucleus and nucleus accumbens, presumably through preferential activation of presynaptic receptors, as assessed by changes in DOPAC levels (Serra et al. 1981). Moreover, lisuride is also reported to reduce DA turnover and synthesis at low doses (Kehr 1977).
In conclusion, our behavioural findings strongly support an effect of lisuride on dopaminergic mechanisms. At low doses it probably has a preferential affinity for presynaptic inhibitor receptors, the activation of which leads to SY and, probably, to PE enhancement. At higher doses it would appear to have chiefly an agonistic effect on the postsynaptic DA-receptors, thereby eliciting SB. 1f this hypothesis is confirmed by biochemical studies, induction of SY in addition to sedation could be used as a simple and sensitive behavioral model for testing drugs acting on presynaptic autoinhibitory DA-receptors. Whatever the type of receptor involved, we should like to stress that SY, specifically stimulated by dopamine agonists, would seem to be a parameter worthy of attention in studying animal behavior.


-Szechtman H et al Sensitization and tolerance to apomorphine in men: yawning, growth hormone, nausea, and hyperthermia Psychiatry Research 1988, 23, 245-255
-Szechtman H Timing of yawns induced by a small dose of apomorphine and its alteration by naloxone Prog Neuro-Psychopharmacol & Biol Psychiat 1984; 8; 743-746