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Genotypic dependency of spontaneous yawning frequency in the rat.

By inbreeding we have obtained two sublines of Sprague-Dawley rats which differ significantly in spontaneous mean yawning frequency (MYF). In generation F21 of the high-yawning (HY) subline MYF was 21.5 yawns/h (y/h) in males and 1.95 y/h in females, at the age of 2 months. In the low-yawning (LY) subline, in generation F16 the MYF was 0.9 y/h in males and only 0.5 y/h in females. During the first 15 days there are no differences in yawning frequency between HY and LY rats. Thereafter yawning increases with age, more steeply in the HY subline. The results of reciprocal crosses between both sublines indicate that the LY character is partially dominant over the HY one.

Age Factors↗

An activation of parvocellular oxytocinergic neurons in the paraventricular nucleus in oxytocin-induced yawning and penile erection.

Intracerebroventricular (ICV) or PVN local injections of oxytocin induce yawning and penile erection, for which a positive feedback mechanism for the PVN oxytocinergic activation is suggested, but this had not been directly substantiated in vivo. We have assessed the behavioral effects and activity of oxytocinergic neurons with double-staining for c-Fos and oxytocin in the PVN after ICV administration of oxytocin in adult male rats. ICV oxytocin injections (50 and 200 ng) dose-dependently induced yawning and penile erection and significantly increased the percentage of c-Fos positive oxytocin neurons in the medial, dorsal and lateral parvocellular subdivision of the PVN. However, increases in the magnocellular portion were not significant. We also found that lithium chloride (LiCl, 0.5 and l.0 mEq), a compound known to activate oxytocinergic neurons, also significantly increased the percentage of c-Fos positive oxytocin neurons in all PVN portions. However, LiCl did not induce yawning and penile erection, but counteracted the oxytocin-induced yawning and penile erection. These results suggest that if the activation of oxytocinergic neurons in the PVN is important for mediating oxytocin-induced yawning and penile erection, a selective activation of parvocellular oxytocinergic neurons in the PVN is likely to be involved.

Animals↗

7-OH-DPAT, unlike quinpirole, does not prime a yawning response in rats.

Repeated treatment in ontogeny with the dopamine (DA) D(2)/D(3) receptor agonist quinpirole is associated with enhanced quinpirole-induced yawning and other behaviors such as vacuous chewing, vertical jumping, and antinociception. To determine if the reputedly DA D(3) agonist (+/-)-2-(dipropylamino)-7-hydroxy-1,2,3, 4-tetrahydronaphthalene (7-OH-DPAT) would prime for yawning in a manner analogous to that for quinpirole, rats were treated for the first 11 days after birth with an equimolar dose of either quinpirole or 7-OH-DPAT (195.4 nmol/kg/day) and tested for agonist-induced yawning in adulthood. While enhanced quinpirole-induced and 7-OH-DPAT-induced yawning was observed in quinpirole-primed rats, acute treatments with quinpirole and 7-OH-DPAT did not produce an enhanced yawing response in 7-OH-DPAT-"primed" rats. Our findings indicate that 7-OH-DPAT, unlike quinpirole, does not prime for quinpirole- or 7-OH-DPAT-induced yawning in rats.

Animals↗

Inhibition of grooming by pilocarpine differs in high- and low-yawning sublines of Sprague-Dawley rats.

A comparative study of the effect of pilocarpine, a muscarinic receptor agonist, on grooming, scored during 45 min via a time-sampling procedure, was carried out on two sublines of male rats selectively bred for high-(HY) and low-yawning (LY) frequency. In one condition, we introduced rats in a novel cage and observed them immediately after receiving an I.P. injection of pilocarpine (0.5-3.75 mg/Kg) or an equivalent volume of saline. Besides grooming, the occurrence of yawns was continuously recorded. In the other condition, we immersed rats in water for 60 s, then they received an I.P. injection of pilocarpine (3.75 mg/Kg) or an equivalent volume of saline and we placed them in an open field, in which we recorded the number of crossed squares. Grooming scores were significantly higher in the condition after water immersion than in the novel situation; in both conditions HY had a grooming response higher than that of LY rats. Pilocarpine produced a dose-dependent inhibition of novelty-induced grooming in HY rats, whereas LY grooming was reduced only with the highest dose. In contrast, yawning increased in a dose-dependent manner with HY rats curve over that of LY animals, except for the highest dose. Pilocarpine inhibited water immersion-induced grooming in both sublines of rats, but it did not reduce grooming as much as it did in the novel condition. Pilocarpine affected distinctly each of the components of grooming, without inhibiting animals locomotor activity. The results indicate that HY rats also have a higher number of grooms than LY rats, and because grooming and yawning can appear after stressful circumstances, HY rats may be used to study the role that both behaviors could have in counteracting the effects of stress. Similarly, HY animals might be utilized to study the underlying neurochemical mechanisms of grooming. This study also indicates that the cholinergic systems exert an inhibitory influence on grooming which contrasts with the excitatory effect on yawning.

Animals↗

Oxytocin increases nitric oxide production in the paraventricular nucleus of the hypothalamus of male rats: correlation with penile erection and yawning.

A dose of oxytocin (50 ng i.c.v.) that induces penile erection and yawning, increased the concentration of NO2- from 0.98 +/- 0.29 to 4.2 +/- 0.79 microM and of NO3- from 5.6 +/- 0.33 to 12.03 +/- 0.99 microM in the dialysate from the paraventricular nucleus of the hypothalamus of male rats, as measured by in vivo microdialysis. NO2- concentration was also increased by [Thr4, Gly7]-oxytocin (100 ng i.c.v. and oxytocin(8) (1 microgram i.c.v.) which also induced penile erection and yawning, but not by oxytocin(1-6) (1 microgram i.c.v.) or oxytocin (7-9) 1 microgram i.c.v.), which were unable to induce these behavioral responses. The oxytocin effect on NO2 concentration, penile erection and yawning was prevented by the oxytocin receptor antagonist. d(CH2)5,Tyr(Me)-Orn8-vasotocin (1 microgram i.e.v.) or by the nitric oxide synthase inhibitor, NG-nitro-1-arginine methyl ester (200 micrograms i.c.v.), but not by the dopamine receptor antagonist, haloperidol (0.5 mg/kg i.p.). The nitric oxide scavenger, hemoglobin (200 micrograms i.c.v.), prevented oxytocin-induced NO2- concentration increase, but was unable to prevent penile erection and yawning. Methylene blue (300 micrograms i.c.v.) an inhibitor of guanylate cyclase, was ineffective on oxytocin-induced NO2- concentration increase, but prevented the behavioral responses. The results suggest that oxytocin induces penile erection and yawning by increasing nitric oxide synthase activity in the cell bodies of oxytocinergic neurons projecting to extra-hypothalamic brain areas and mediating the behavioral responses.

Animals↗

Contagious yawning: the role of self-awareness and mental state attribution.

Contagious yawning is a common, but poorly understood phenomenon. We hypothesized that contagious yawning is part of a more general phenomenon known as mental state attribution (i.e. the ability to inferentially model the mental states of others). To test this hypothesis we compared susceptibility to contagiously yawn with performance on a self-face recognition task, several theory of mind stories, and on a measure of schizotypal personality traits. Consistent with the hypothesis, susceptibility to contagiously yawn was positively related to performance on self-face recognition and faux pas theory of mind stories, and negatively related to schizotypal personality traits. These data suggest that contagious yawning may be associated with empathic aspects of mental state attribution and are negatively affected by increases in schizotypal personality traits much like other self-processing related tasks.

Adult↗

Reduction of drug-induced yawning and penile erection and of noncontact erections in male rats by the activation of GABAA receptors in the paraventricular nucleus: involvement of nitric oxide.

The effect of muscimol, a GABAA receptor agonist, injected into the paraventricular nucleus (PVN) of the hypothalamus on drug-induced (apomorphine, oxytocin and NMDA) yawning and penile erection, and on the increase in the concentration of NO2- and NO3- occurring in the paraventricular dialysate in these experimental conditions, was studied in male rats. Muscimol (50, 100 and 200 ng) reduced, in a dose-dependent manner, penile erection and yawning induced by apomorphine (50 ng), oxytocin (30 ng) and NMDA (50 ng) delivered into the PVN. The reduction of penile erection and yawning was parallel to a reduction of the concomitant NO2- and NO3- increase that occurs in the paraventricular dialysate in this experimental condition. In contrast, baclofen (200 ng), a GABAB receptor agonist, was ineffective. The muscimol effects on drug-induced penile erection, yawning and NO2- increase were prevented by the prior administration of bicuculline (250 ng into the paraventricular nucleus). Muscimol (200 ng) but not baclofen (200 ng), injected into the PVN, reduced both noncontact erections in male rats placed in the presence of an inaccessible receptive female, and also the NO2- increase that occurs in the paraventricular dialysate in this experimental condition. As found with drug-induced penile erection, the muscimol reduction of noncontact erections and of NO2- increase was prevented by bicuculline. The present results show that the activation of GABAA receptors in the PVN reduces yawning and penile erection induced by drugs or physiological stimuli by reducing the increase in NO activity that occurs in this hypothalamic nucleus in these experimental conditions.

Animals↗

Involuntary stretching during yawning in patients with pyramidal tract lesions: further evidence for the existence of an independent emotional motor system.

A variety of associated movements have been described in patients with pyramidal tract lesions. We report three patients in whom involuntary stretching of an otherwise plegic arm could be observed during yawning. These patients had radiologically verified lesions at different levels of the pyramidal tract. As yawning and stretching are an automatic behavioural pattern in animals, it is likely that stretches during yawning in man are also an automatic motor pattern, usually inhibited in the presence of an intact corticospinal tract. The physiological function of yawning is unclear at present. Yawning might be the somatomotor manifestation of a particular emotional state characterized by boredom and fatigue. Our observation that movements of an otherwise plegic arm occur in patients with pyramidal tract lesions supports therefore the concept of an emotional motor system which has an independent input to motoneurones in the brain stem and the spinal cord.

Adult↗

Apomorphine-induced blinking and yawning in healthy volunteers.

Yawning and spontaneous blink rate (SBR) are two physiological reflexes which have been incompletely examined but one neurobiological step of these two behaviours seems, at least in part, dopamine-dependent. The reference dopaminergic agonist, apomorphine hydrochloride (0.5, 1, and 2 micrograms kg-1 s.c.), was compared with a placebo in a double-blind latin-square design, and was shown to induce yawning and increase SBR in a population of eight healthy volunteers. These two behavioral effects were not dose-related. The individual SBR differences were correlated with the individual number of yawns for all the four treatments at the 10-30 min interval. Thus, parallel yawning and SBR behaviour suggests a similar pharmacological mechanism. Apomorphine-induced yawning and blinking may be therefore of use in the evaluation of central dopaminergic pathways in man.

Adult↗

Effect of time-of-day on the yawning response to apomorphine in normal subjects.

The yawning response to the dopamine (DA) receptor agonist apomorphine HCl (Apo, 7 microg/kg s.c.) and placebo (physiological saline) were examined in two groups of normal men. One group (n = 11) was investigated in the morning and the other group (n = 16) in the afternoon. The frequency of yawning was polygraphically monitored for 60 min following injection. Apo increased yawning compared with placebo when given in the morning (p < 0.02), but not when given in the afternoon. Yawning frequency was increased after both Apo (p < 0.01) and placebo (p < 0.025) when given in the morning compared with responses in the afternoon. These results suggest that yawning frequency with both Apo and placebo is influenced by time of day, possibly as a result of diurnal variation in DA receptor sensitivity.

Adult↗

[Yawning and temporal lobe epilepsy].

Temporal lobe epilepsy is a partial epileptic disorder in which mesial structures are responsible for the principal ictal symptoms. Its characteristic feature is the recurrence of simple and complex partial seizures, associated with postictal confusion and amnesia of the event. The facilitating effect of NREM sleep on the propagation of the seizure, as well as the sleep abnormalities provoked by epilepsy were evident in our two patients. Yawning is a physiological reflex induced by arousal and drowsiness and may appear in different neurological conditions. Its relation with epilepsy of limbic origin has been rarely reported. We describe in a 95 year old male patient, the occurrence of yawning followed by complex partial seizure during a state of drowsiness. His EEG showed independent bilateral interictal foci of temporal sharp waves and after being medicated with carbamazepine 400 mg/day, the episode did not recur. Another patient, a 17 year old female, displayed complex partial seizures and secondarily generalized seizures with yawning during the posictal period, after naps. The EEG was normal and her polysomnography showed bilateral synchronous temporal spikes and slow waves with secondarily generalization during stage 2 of NREM sleep that produce paroxysmal microarousals and increased stages 1 and 2 of NREM sleep and REM sleep diminished. After being medicated with divalproex sodium 750 mg/day, she suffered no further seizures. Temporal lobe epilepsy, sleep-wake cycles and yawning seem not only to share the same anatomic structures but also the same neurochemical mechanisms. The fact that endogenous opiods are considered as part of a protective system that stop and prevent seizures may allow us to postulate that yawning would be the expression of the endogenous opiods induced mechanisms that stop and prevent the recurrence of the temporal lobe epilepsy. Another hypothesis may be that this is only a particular form of temporal lobe epilepsy.

Adolescent↗

[Yawning].

Yawning is a normal reflex triggered by arousal, drowsiness, boredom, hunger and emotional conditions and it is associated to several neurological diseases and drug abuse. Its wide presence in the phylogenetic vertebrate scale and even in human fetuses as young as 12 weeks directed the search for the common anatomic and biochemical mechanisms involved. The demonstration that yawning is not connected with high CO2 or low O2 blood levels left aside a prevalent metabolic hypothesis. Its close relationship with the sleep-wake cycle, specially in moments previous to falling asleep and after awaking has been related to changes in personal situation and activity. A single component of this reflex which is to be found exclusively in humans, is the fact that yawning is contagious. Thus, it is considered a component of the adaptative mechanism that is part of the surveillance reflex, becoming a significant paralinguistic evolutive expression aimed at protection and social cohesion. The common anatomical structures and neurochemical systems taking part in yawning, the sleep-wake cycle and the temporal lobe epilepsy may imply that yawning results from a set of protective systems induced by endogenous opiods which intervene in the inhibition and prevention of the temporal lobe epileptic seizures.

Epilepsy, Temporal Lobe↗

Ontogeny of two cholinergically mediated central effects: stereotyped yawning and potentiation of head-shaking.

The ontogenetic course of two cholinergically mediated central neuropharmacological effects, yawning and potentiation of head-shaking induced by D-amphetamine (5 mg/kg), was explored in developing rats. Physostigmine (0.1 mg/kg) and pilocarpine (4 mg/kg) evoke stereotyped yawning in neonatal rats, the effect declining in the middle of the second week of life. Both cholinomimetic drugs strongly potentiate amphetamine induced head-shaking between the 4th and 10th postnatal days. Pilocarpine per se is capable of inducing head-shaking, in the absence of amphetamine, in rats from 8 to 12 days. Infant rat yawning and head-shaking are blocked by scopolamine (5 mg/kg). Nicotine (0.1 mg/kg) potentiates head-shaking but inhibits yawning. Yawning is also depressed by D-amphetamine. The early maturation of these cholinergic effects is discussed in comparison to the later maturation of several forebrain cholinergic systems.

Animals↗

Pre- and post-synaptic dopaminergic receptors involved in apomorphine-induced yawning.

The temporal course of yawning behavior elicited by increasing doses of apomorphine (APO), from 0.01 to 10 mg/kg, was studied experimentally in adult albino rats. In the higher dose range a great prolongation of drug induced yawning latency is observed. This result is explainable by postulating differences in sensitivity of two sets of dopaminergic (DA) receptors: low threshold presynaptic DA receptors which, when activated, disinhibit yawning, and high threshold postsynaptic DA receptors inhibiting yawning. Apomorphine in high doses can entirely suppress physostigmine-elicited yawning.

Animals↗

Yawning and suppression of exploration in amphetamine-treated rats, incompatibility with the autoreceptor hypothesis.

The hypothesis that yawning and suppression of exploration, induced by low doses of dopamine agonists, are mediated by stimulation of dopamine autoreceptors was tested by studying the influence of amphetamine on these behavioural models and on extracellular levels of dopamine sampled by microdialysis. Behaviour was measured in a holeboard apparatus. A low dose of amphetamine (0.2 mg/kg) caused slight activation of habituated rats. The same dose of amphetamine completely counteracted the decrease in extracellular dopamine levels caused by pergolide (0.02 mg/kg) and, instead, elevated the dopamine levels to 300% above baseline. The same or higher doses of amphetamine (0.5-1.0 mg/kg) did not completely antagonise suppression of exploration or yawning induced by apomorphine (0.05 mg/kg) or pergolide (0.02 mg/kg). The results suggest that both yawning and suppression of exploration induced by low doses of dopamine agonists are not mediated by dopamine autoreceptors, since these behaviours could be elicited when the extracellular levels of dopamine were elevated above baseline. The alternative hypothesis that these behaviours are mediated by sensitive post-synaptic receptors is suggested. It was also found that combined treatment with SCH 23390 (0.05 mg/kg) and amphetamine (2 mg/kg) induced yawning, which further supports the new hypothesis.

Amphetamine↗

Yawning is elicited by D2 dopamine agonists but is blocked by the D1 antagonist, SCH 23390.

The subtype of dopamine (DA) receptors mediating the yawning response to DA agonists was determined in rats. Yawning was elicited both by the mixed D1-D2 agonist apomorphine and by the specific D2 agonist LY 171555, but not by the selective D1 agonist SKF 38393. Both apomorphine- and LY 171555-induced yawning were antagonized not only by the selective D2 antagonist sulpiride but, unexpectedly, also by the selective D1 antagonist SCH 23390. The results suggest that DA receptors mediating the yawning response are of the D2 type, and that these receptors are connected with D1 receptors in such a way that the blockade of the latter results in the functional inactivation of the former.

Animals↗

5-HT1A receptor agonists prevent in rats the yawning and penile erections induced by direct dopamine agonists.

The new compound (+) S-20499, an amino chromane derivative (8[-4[N-(5-methoxychromane-3yl)N-propyl]aminobutyl] azaspiro[4-5] décane-7,9 dione), is a high affinity full 5-HT1A agonist. We have investigated its effects on dopaminergic transmission. (+) S-20499 displayed a 10(-8) M affinity for D2 dopamine (DA) receptors, 100 fold lower than for 5-HT1A receptors. The hypothermic effect of the drug was reversed by haloperidol in mice, suggesting that it behaves as a direct dopamine agonist. However, increasing doses of (+) S-20499 induced neither yawning nor penile erections, which constitute characteristic responses of direct DA agonists administered at low doses. In addition, (+) S-20499 prevented the apomorphine (100 micrograms/kg SC) induced yawning and penile erections. This inhibition appears to result from the stimulation of 5-HT1A receptors since it is an effect shared by both buspirone (from 5 mg/kg) and 8-OH-DPAT (from 0.10 mg/kg). In addition, when rats are treated with the 5-HT1A receptor antagonist tertatolol (2-5 mg/kg; SC), increasing doses of (+) S-20499 elicit the expected yawns and penile erections. It is concluded that the 5-HT1A agonist property opposes to that of D2 dopamine receptor stimulation with regard to yawning and penile erections.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Do autoreceptors mediate dopamine agonist--induced yawning and suppression of exploration? A critical review.

The hypothesis that stimulation of dopamine autoreceptors is the mechanism by which dopamine agonists induce yawning and suppression of exploration is critically examined. It is shown that the relation between reduced extracellular dopamine levels, assessed by microdialysis, and behavioural effects of dopamine agonists, a dopamine synthesis inhibitor and a granule storage blocker is highly inconsistent. The time-course and duration of the behavioural effects of dopamine agonists differ from the reduction of extracellular dopamine. Amphetamine cotreatment is shown to increase dopamine levels, while yawning and suppression of exploration can still be induced. The data strongly indicate that autoreceptors are not the mediators of these behavioural effects. It is proposed that postsynaptic receptors mediate dopamine agonist induced yawning and suppression of exploration. Evidence is also presented showing that yawning and suppression of exploration are not functionally equivalent.

Animals↗