Yawning Behavior Research Articles

The sound of yawns makes geladas yawn

Yawning is undeniably contagious and hard to resist. Interestingly, in our species, even the mere sound of a yawn can trigger this contagious response, especially when the yawner is someone familiar. Together with humans, one other mammal species is known to produce loud and distinct vocalisations while yawning, Theropithecus gelada. Geladas are known for their complex social interactions and rich vocal communication, making them intriguing subjects for studying yawning behaviour. To explore the contagious effect of yawn sounds on geladas, we conducted playback experiments in a zoo-housed colony with animals living in two groups. We exposed them to yawn sounds (Test) or affiliative grunts (Control) produced by males from either their own group or the other one. The results were remarkable, as simply hearing yawn sounds led to yawn contagion in geladas, with multiple responses observed when the yawns came from members of their own group. This finding adds a significant contribution to the research on mimicry and behavioural contagion in primates. Moreover, it raises intriguing questions about the involvement of sensory modalities beyond visual perception in these phenomena.

The Role of Empathic Concern and Gender on Interspecific Contagious Yawning in Humans.

Interspecific contagious yawning (CY), whereby yawns from one species trigger yawning in different species, has now been reported across various taxa. This response to human yawning appears common among animals in captivity and has been interpreted as an empathic response towards human handlers/caregivers. A recent study found that humans also display interspecific CY, though this response was not modulated by proxies of empathic processing (i.e., phylogenetic relatedness or social closeness to the animals). Here, we explored this relationship more explicitly by assessing how interspecific CY to yawns from common household pets relates to self-reported empathic concern. Participants (N = 103) completed a survey measuring empathic concern and then reported on their yawning behavior following exposure to a control condition or yawning images either from domesticated cats or domesticated dogs. The results provide further evidence for interspecific CY in humans, but empathic concern was negatively predictive of this response. There was also no sex difference in interspecific CY, though when comparing the sexes across CY conditions, women reported a higher frequency of yawning in response to dog yawns, and men reported a higher frequency of yawning in response to cat yawns. Overall, these findings do not support a strong connection between interspecific CY and empathy or emotional contagion.

Towards Reliable Driver Drowsiness Detection Leveraging Wearables

Driver drowsiness is a significant factor in road crashes. However, existing solutions for driver drowsiness detection have major drawbacks of requiring special hardware, constrained recording conditions, and cannot handle the asynchronous and contradictory nature of multiple indicators. In view of this, we propose FDWatch, a novel drowsiness detection system that exploits the low-cost Photoplethysmogram (PPG) sensor and motion sensor integrated into wrist-worn devices. We design a set of novel algorithms to extract multiple drowsiness-related indicators covering major categories of human factors. In particular, we demonstrate that commodity PPG sensors can be utilized to detect yawning behavior; it contributes as an important indicator for drowsiness detection. The core of FDWatch is based on the Dempster-Shafer evidence theory. It considers different indicators as evidence describing the state of the driver from different angles. To make the extracted indicators applicable to Dempster-Shafer evidence theory, we employ backpropagation neural networks to obtain the basic probability assignment. Moreover, we propose a similarity-distance-based method to handle evidence conflicts. Extensive experiments with real-road driving data show that FDWatch can accurately detect driver drowsiness with a missing alarm rate of 3.57% and a false alarm rate of 3.68%.

The Effects of Alcohol and Social Isolation on Yawning Behavior in Adult Male Rats, Treated with Opioid Receptor Agonist and Antagonist

The number of 88 rats was chosen, after 21 days, they were ablactated and categorized them as following groups:
 The control group 1 has a cage of 8 rats in a social condition. After 6 weeks of saline injection (1mg / kg), the yawning behavior is recorded for 60 minutes. Group 2 in social conditions of receiving ethanol for 2 months, each serving of 600 mg / kg. Group 3 social isolation without treatment with agonist and antagonist, Opioid and alcohol drugs in a separate cage, each cage has one rat. After 6 weeks, It is recorded the yawning was cured for 60 minutes. Group 4 social isolation for 6 weeks and then treatment with alcohol agonist (1200 mg / kg) after 30 minutes of yawing behavior is recorded for 60 minutes. Group 5 Social isolation after 6 weeks of treatment with opioid drugs (5mg / kg of morphine) after 30 minutes of yawing behavior is recorded for 60 minutes. Group 6 social isolation after 6 weeks of morphine + alcohol antagonist treatment after 30 minutes of yawing behavior is recorded for 60 minutes. Group 7 social isolation followed by 6 weeks of treatment with antagonist alcohol (naltrexone), 10 mg / kg, after 30 minutes of yawing behavior is recorded for 60 minutes. Group 8 Social isolation after 6 weeks of treatment with antagonist morphine (naloxone) 1 mg / kg of bad breath after 30 minutes of yawing behavior is recorded for 60 minutes. Group 9 social isolation followed by 6 weeks of treatment with antagonist alcohol + morphine after 30 minutes for 60 minutes of yawing behavior is recorded for 60 minutes. Group 10 social isolation followed by 6 weeks of treatment with antagonist alcohol + morphine antagonist after 30 minutes for 60 minutes of yawing behavior is recorded for 60 minutes. Group 11 Social isolation after 6 treatments with antagonist morphine + alcohol followed after 30 minutes for 60 minutes of yawing behavior is recorded for 60 minutes.
 Injection of alcohol chronically reduces yawning, but alcohol injections in conditions of social isolation increase the number of yawns. Antagonist injection of naltrexone prior morphine in conditions of social isolation of yawning. Injection of morphine in conditions of social isolation does not change the number of yawning. Injection of morphine antagonist (naloxone) prior to antagonist of alcohol (naltrexone) in conditions of social isolation increases yawn. Also, the injection of morphine antagonist (naloxone) prior to alcohol into social isolation causes an increase in the number of yawns. Alcohol injection before morphine in conditions of social isolation increases the number of yawns.
 It seems that the stress of social isolation by decreasing alcohol and morphine function increases the number of yawns.

Neural pathways from the central nucleus of the amygdala to the paraventricular nucleus of the hypothalamus are involved in induction of yawning behavior due to emotional stress in rats

As yawning is often observed in stressful or emotional situations such as tension and anxiety, this suggests that yawning can be considered to be an emotional behavior. However, the neural mechanisms underlying emotion-induced yawning remain unclear. It is well known that the hypothalamic paraventricular nucleus (PVN) is the most important brain structure for induction of yawning behavior. We previously showed that induction of yawning involves the central nucleus of the amygdala (CeA), as well as the PVN. Therefore, emotion-induced yawning could potentially be induced through activation of the direct/indirect neural pathways from the CeA to the PVN. Our present study used a combination of retrograde tracing (injection of Fluoro-Gold (FG) into the PVN) and c-Fos immunohistochemistry to examine the neural pathways that evoke emotion-induced yawning. We additionally performed lesion experiments on the CeA using ibotenic acid, a neurotoxin, to determine whether the CeA is involved in the induction of emotion-induced yawning. Emotional stress by fear conditioning induced yawning behavior, and induced expression of double-labeled cells for c-Fos and FG in the bed nucleus of the stria terminalis (BNST), but not in the CeA. Furthermore, the CeA lesions caused by ibotenic acid abolished the induction of emotion-induced yawning. These results suggest that a neural pathway from the CeA to the PVN via the BNST may be primarily involved in the induction of emotion-induced yawning behavior.

Interspecific Contagious Yawning in Humans

Contagious yawning, or the reflexive tendency to yawn following the detection of yawning in others, is well-documented among humans and a growing number of social vertebrates. While the most common form of yawn contagion occurs between conspecifics, some non-human animals in captivity have been reported to yawn in response to yawns from human handlers/caregivers. The current research sought to provide the first formal investigation of whether people yawn contagiously in response to yawns from non-human animals. In addition, this study aimed to test whether this response was modulated by phylogenetic relatedness and domestication/social closeness. A total of 296 participants from Amazon Mechanical Turk self-reported on their yawning behavior following exposure to a (1) control (non-yawning) condition or a compilation of yawning stimuli either from (2) fish, (3) amphibians, (4) reptiles, (5) birds, (6) non-primate mammals, (7) apes, or (8) domesticated cats and dogs. The results provide strong support for interspecific yawn contagion. However, neither the propensity to yawn (binary) nor total yawn frequency varied significantly across interspecific conditions. Overall, these findings suggest that the mechanisms governing yawn contagion can be activated by varied forms of yawning stimuli, including those from distantly related and unfamiliar species.

Two forms of yawning modulation in three months old infants during the Face to Face Still Face paradigm.

The last decades have seen an increasing interest in the phenomenon of yawning and the dynamics of its modulation, yet no widespread consensus exists on its origins and potential functions. Although most scholars have focused on its potential physiological functions, e.g., related to thermoregulation, arousal modulation or cortisol levels and distress, an emerging line of research has been also investigating the social implications of yawning, including its hypothesized relationship with empathy. In order to explore the dynamics of yawning modulation in infants, we investigated whether a social perturbation–like the one induced by the Face to Face Still Face paradigm, a procedure designed to assess socio-emotional regulation in infants–affects yawning and self-touch hand movements behavior in three-months old infants. As the Still Face episode represents a source of mild distress, we hypothesized that during this phase yawns would be more frequent. Moreover, through the use of path analysis, we investigated potential dynamics of facilitation, inhibition or covariance between the frequencies of these behavioral patterns. Our results showed a sharp increase in self-touch hand movements as well as in the likelihood of yawning during the stressful phase of the procedure (still-face) compared with the two minutes of face-to-face interaction and the reunion episode. Regressions also showed a higher incidence of yawns among girls, consistently with the hypothesis that the analysis of yawning behavior might capture subtle differences in regulatory strategies of infants, possibly related to the transient sex-specific activation of the hypothalamic-pituitary-gonadal axis known as mini-puberty. The path analysis showed a greater consistency between the frequencies of self-touch hand movements during the three episodes of the procedure, compared with yawning. This finding could be a result of distinct yawning-regulating mechanisms being at play in different conditions, e.g., a modulation related to stress and one to social interaction. Taken together, these results suggest that human yawning regulation is an irreducibly complex and multifaceted phenomenon since early age. Moreover, the gender differences highlighted might suggest an early diversification in yawning modulation.

Transgenerational evidence of increases in dopamine D2 receptor sensitivity in rodents: Impact on sensorimotor gating, the behavioral response to nicotine and BDNF.

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 (DAD2) receptor sensitivity in adult animals. We investigated if increased DAD2 sensitivity would be passed to the next (F1) generation, and if these animals demonstrated sensorimotor gating deficits and enhanced behavioral responses to nicotine. Male and female rats were intraperitoneal (IP) administered quinpirole (1 mg/kg) or saline (NS) from postnatal day (P)1-21. Animals were either behaviorally tested (F0) or raised to P60 and mated, creating F1 offspring. Experiment 1 revealed that F1 generation animals that were the offspring of at least one NQ-treated founder increased yawning behavior, a DAD2-mediated behavioral event, in response to acute quinpirole (0.1 mg/kg). F1 generation rats also demonstrated increased striatal β arrestin-2 and decreased phospho-AKT signaling, consistent with increased G-protein independent DAD2 signaling, which was equal to F0 NQ-treated founders, although this was not observed in all groups. RNA-Seq analysis revealed significant gene expression changes in the F1 generation that were offspring of both NQ-treated founders compared to F0 NQ founders and controls, with enrichment in sensitivity to stress hormones and cell signaling pathways. In Experiment 2, all F1 generation offspring demonstrated sensorimotor gating deficits compared to controls, which were equivalent to F0 NQ-treated founders. In Experiment 3, all F1 generation animals demonstrated enhanced nicotine behavioral sensitization and nucleus accumbens (NAcc) brain-derived neurotrophic factor (BDNF) protein. Further, F1 generation rats demonstrated enhanced adolescent nicotine conditioned place preference equivalent to NQ-treated founders conditioned with nicotine. This represents the first demonstration of transgenerational effects of increased DAD2 sensitivity in a rodent model.

Yawn contagion promotes motor synchrony in wild lions, Panthera leo

Yawning, a fixed action pattern, is widespread in almost all vertebrate taxa. Several hypotheses have been proposed to explain the functions of yawning. These hypotheses, not mutually exclusive, can be conventionally arranged according to both physiological (e.g. drowsiness hypothesis: yawning when switching between sleep and being awake; arousal hypothesis: yawning in contexts of high social tension) and social communicative domains (e.g. contagion hypothesis, activity synchronization hypothesis). Owing to their high social cohesion and synchronized group activity, wild lions are a good model to investigate both spontaneous yawning from the physiological domain and, possibly, contagious yawning, from the social communicative domain. We videorecorded two groups of lions in the Makalali Reserve (Limpopo region, South Africa) and analysed their yawning behaviour. Spontaneous yawning was particularly frequent when the lions were relaxed and, in agreement with the 24 h activity cycle typical of the species, was similarly distributed over the night and day. These findings support the drowsiness hypothesis predicting that yawning is linked to the transition between sleeping and waking (and vice versa). Lions did not show high levels of yawning during competition over clumped food such as carcasses; hence, the arousal hypothesis was not supported. We found that yawn contagion was present, supporting the contagion hypothesis and the activity synchronization hypothesis. Our findings suggest that the convergence of motor behaviour triggered by yawn contagion (to our knowledge never explored in any other species) could represent an important tool to shed light on the adaptive and immediate benefits that underlie the evolution of the yawn contagion phenomenon in human and nonhuman animals. • Lions yawn when they are relaxed and engage in social affiliation. • The arousal state seems to inhibit yawning in wild lions. • Wild lions are infected by others' yawns. • Yawn contagion facilitates motor convergence thus favouring lion group synchrony.

The Effects of Dopamine and Serotonin on Yawning Behavior in the Rat Model of Social Isolation

A sample of 80 Male rats (21-day post weaning) were chosen, and were put for 6 weeks in separate cages with black plastic buffers. Eight rats were put in one group of 8 rats in a single cage (the control group) and the rest were put in individual cages: one male rat in each cage. In group 1 or the control group (social conditions) 8 rats were put in one cage. They received saline carrier and their yawning behavior was recorded for 60 minutes. Group 2 (n=8; in separate cages) (social isolation conditions) received no treatment with serotonin and dopamine agonist and antagonist and were kept in separate cages with one rat in each cage. Their yawning behavior was also recorded for 60 minutes. Group 3 (n=8; in separate cages) included the rats that received Apomorphine (dopamine agonist) at a dose of 0.08 mg/kg via subcutaneous injection (SC), and their yawning behavior was recorded for 60 minutes. Rats in group 4 (n=8; in separate cages) received serotonin agonist (m-CPP) at a dose of 0.5 mg/kg via subcutaneous injection, and their yawning behavior was recorded for 60 minutes. Group 5 (n=8; in separate cages) included rats that received Serotonin Antagonist (Mianserin) at a dose of 0.2 mg/kg via subcutaneous injection, and their yawning behavior was recorded for 60 minutes. Group 6 (n=8; in separate cages) included rats receiving dopamine antagonist (haloperidol) at a dose of 0.1 mg/kg via Intraperitoneal (IP) injection, and their yawning behavior was recorded for 60 minutes. Group 7 (n=8; in separate cages) included rats receiving Serotonin antagonist (Mianserin) at a dose of 0.2 mg/kg via subcutaneous injection 15 minutes before injection of apomorphine (dopamine agonist) and their yawning behavior was recorded for 60 minutes. Rats in group 8 (n=8; in separate cages) received dopamine antagonist (haloperidol) at a dose of 0.1 mg/kg via intraperitoneal injection (IP) 15 minutes before the injection of serotonin agonist (m-ccp), and their yawning behavior was recorded for 60 minutes. Rats in group 9 (n=8; in separate cages) received Apomorphine (dopamine agonist) at a dose of 0.08 mg/kg and Serotonin agonist (m-CPP) injected subcutaneously (SC) at a dose of 0.5 mg/kg and their yawning behavior was recorded for 60 minutes. Group 10 (n=8; in separate cages) included rats that received dopamine antagonists (haloperidol) at 0.1 mg/kg via intraperitoneal injection (IP) and antagonist serotonin (Mianserin) at 0.2 mg/kg injected subcutaneously and their yawning belabor was recorded for 60 minutes. Dopamine agonist (apomorphine) and serotonin antagonist (Mianserin) induce yawning in the social conditions and injection of haloperidol (dopamine antagonist) before serotonin agonist (m-ccp) reduces yawning in social conditions. Yawning is different in social conditions and social isolation conditions. Using Meta-Chlorophenylpiperazineserotonin (serotonin agonist), Mianserin (serotonin antagonist), apomorphine (dopamine agonist), haloperidol (dopamine antagonist) the role of serotonin and dopamine in yawning, fear, erection etc. can be investigated as a model for human studies.

Blood oxytocin concentration positively predicts contagious yawning behavior in children with autism spectrum disorder.

Research suggests that children with autism spectrum disorder (ASD) may have reduced empathy, as measured by an impaired contagious yawn response, compared to typically developing (TD) children. Other research has failed to replicate this finding, instead attributing this phenomenon to group differences in attention paid to yawn stimuli. A third possibility is that only a subgroup of children with ASD exhibits the impaired contagious yawn response, and that it can be identified biologically. Here we quantified blood concentrations of the "social" neuropeptide oxytocin (OXT) and evaluated yawning behavior and attention rates during a laboratory task in children with ASD (N = 34) and TD children (N = 30) aged 6-12 years. No group difference in contagious yawning behavior was found. However, a blood OXT concentration × group (ASD vs. TD) interaction positively predicted contagious yawning behavior (F1,50 = 7.4987; P = 0.0085). Specifically, blood OXT concentration was positively related to contagious yawning behavior in children with ASD, but not in TD children. This finding was not due to delayed perception of yawn stimuli and was observed whether attention paid to test stimuli and clinical symptom severity were included in the analysis or not. These findings suggest that only a biologically defined subset of children with ASD exhibits reduced empathy, as measured by the impaired contagious yawn response, and that prior conflicting reports of this behavioral phenomenon may be attributable, at least in part, to variable mean OXT concentrations across different ASD study cohorts. Autism Res 2019, 12: 1156-1161. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism may contagiously yawn (i.e., yawn in response to another's yawn) less often than people without autism. We find that people with autism who have lower levels of blood oxytocin (OXT), a hormone involved in social behavior and empathy, show decreased contagious yawning, but those who have higher blood OXT levels do not differ in contagious yawning from controls. This suggests that decreased contagious yawning may only occur in a biologically defined subset of people with autism.

Central nucleus of the amygdala is involved in induction of yawning response in rats

Yawning behavior is characterized by mouth opening accompanied by deep inspiration, as well as arousal response, and is often observed not only in states of boredom or drowsiness, but also in stressful emotional situations in humans and animals. These phenomena suggest that yawning response may be an emotional behavior, possibly through activation of the central nucleus of amygdala (CeA), which is a critical region for emotional responses. However, the involvement of the CeA in triggering yawning remains unknown. Here, we investigated whether neuronal activation of the CeA by microinjection of L-glutamate into the CeA is able to induce stereotyped yawning responses in anesthetized, spontaneously breathing rats. In addition, we assessed the effects of the CeA stimulation on the activation of oxytocin (OT) and CRF (corticotropin-releasing factor) neurons in the paraventricular nucleus of the hypothalamus (PVN), which is responsible for induction of yawning, using c-Fos immunohistochemistry. Microinjection of L-glutamate into the CeA causes an initial depressor response in the blood pressure and an arousal shift on the electrocorticogram followed by a single inspiration, which is the same as the typical pattern of the stereotyped yawning response induced by the PVN stimulation. In addition, the CeA stimulation activated the neuronal activities of both OT and CRF neurons in the PVN, as well as yawning responses. These results indicate that activation of the CeA is involved in the induction of yawning response, suggesting that yawning is an emotional behavior.

In vivo Behavioral Characterization of ML417, a Novel D3 Dopamine Receptor‐selective Agonist

Dopamine receptor (DAR) agonists are important in the therapeutics of Parkinson's disease, Restless Legs Syndrome, and other neurologic disorders. Dopamine receptors are divided into D1‐like (D1R and D5R) and D2‐like (D2R, D3R, and D4R) subcategories. Subtype‐selective DAR agonists can potentially impart pharmacologic benefits while decreasing adverse effects seen with nonselective treatments. However, significant homology exists among the DAR subtypes, especially D2Rs and D3Rs rendering the development of subtype‐selective agonists challenging. Using a high‐throughput screening drug discovery program, we have identified and optimized a highly selective and potent D3R agonist (ML417) as determined using in vitro assays. We also found that ML417 exhibited good pharmacokinetics in mice with a t1/2 of 3–4 hrs in both plasma and brain. In this study, we tested ML417 using several behavioral paradigms in rats. Pramipexole and quinpirole, two relatively non‐selective D2R/D3R agonists in clinical use, were utilized as comparators. All behavioral experiments were approved by the NIH Institutional Animal Care and Use Committee (IACUC). Assessment of locomotor activity was carried out in an open field. Rat behavior was recorded with horizontal and vertical video cameras over a period of 90 mins following i.p. administration. Locomotor activity was tracked with ANY‐maze® software. Yawning ‐ a behavior mediated by D3R activation ‐ was scored by a blinded rater. Rats received multiple doses of ML417, quinpirole or pramipexole in a pseudorandom fashion for all studies. Stereotypies, catalepsy, and other adverse effects were measured, but were not significant at any dose of the drugs tested. During the initial 30 mins after drug administration, quinpirole and pramipexole induced dose‐dependent hypolocomotion (distance traveled or rotational behaviors) in the open field, as has been observed previously. ML417 similarly induced hypolocomotion during the initial 30 min in the open field, but only at the highest dose tested (20 mg/kg). In contrast, between 60–90 mins in the open field, the rats treated with either quinpirole and pramipexole became hyperactive, vs. controls, whereas the animals treated with ML417 were not different from vehicle‐treated animals. These differences in the locomotor effects of ML417 vs. quinpirole or pramipexole during the 60–90 time period post‐drug administration may be due to the D3R selectivity of ML417. We also observed with the 20 mg/kg dose, that ML417 induced significant yawning behavior, which is a known D3R‐mediated behavioral response. These results suggest that ML417 is capable of stimulating the D3R in vivo and does not result in observable side effects. These behavioral effects can be differentiated from non‐ or less‐selective D2‐like DAR agonists. Further studies utilizing ML417 in animal models of disease states, such as Parkinson's disease, are warranted and will enhance our understanding of the role of D3R stimulation in the treatment of neurological disorders.Support or Funding InformationNIH IRPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Yawning: a cue and a signal

Yawning behaviour has been associated with a variety of physiological and social events and a number of corresponding functions have been attributed to it. Non-directed (self-directed behaviour) and directed yawning (display behaviour) might nonetheless encompass all expressions of yawning, although it is difficult to differentiate one type from the other in a social context. Here we analysed more fully the data from a study in which four combinations of sensory cues were presented to pairs of either cage mate or stranger rats. The aim of the re-analysis was to demonstrate that non-directed and directed yawning might be identified by their distinctive functions. All pairs of rats used olfactory cues to recognise each other as stranger or cage mate companions, but only stranger rats used auditory cues to detect and respond to each other’s yawning. Increasing defecation rates (i.e. an index of emotional reactivity) inhibited yawning in cage mate rats such that yawning frequency reflected each rat’s physiological state. These results suggest that non-directed yawning functions as a cue in cage mate rats and directed yawning as a signal in stranger rats. We hypothesize that cue yawning might be a regulatory act that animals perform to adjust muscle tone for a coordinated change of state. Signal yawning might indicate the physiological capacity of rats in male-male conflicts.

Emotional stress evoked by classical fear conditioning induces yawning behavior in rats

Yawning is often observed not only in a state of boredom or drowsiness but also in stressful emotional situations, suggesting that yawning is an emotional behavior. However, the neural mechanisms for yawning during stressful emotional situations have not been fully determined, though previous studies have suggested that both parvocellular oxytocin (OT) and corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) are responsible for induction of yawning. Thus, using ethological observations and c-Fos immunohistochemistry, we examined whether emotional stress evoked by classical fear conditioning is involved in induction of yawning behavior in freely moving rats. Emotional stress induced yawning behavior that was accompanied by anxiety-related behavior, and caused neuronal activation of the central nucleus of the amygdala (CeA), as well as increases in activity of both OT and CRF neurons in the PVN. These results suggest that emotional stress may induce yawning behavior, in which the neuronal activation of the CeA may have a key role.

Dopaminergic D2-like agonists produce yawning in the myelin mutant taiep and Sprague–Dawley rats

Systemic administration of D2-like dopaminergic-receptor agonists increases yawning behavior. However, only a few studies have been done in animals with pathological conditions. The taiep rat is a myelin mutant with an initial hypomyelination followed by progressive demyelination, being the brainstem one of the most affected areas. In our experiments, we analyzed the effects of systemic administration of the D2-family agonists and antagonists on yawning behavior, and correlated them with the lipid myelin content in the brainstem and other areas in the central nervous system (CNS) in 8month old male taiep and Sprague–Dawley rats. Subjects were maintained under standard conditions in Plexiglas cages with a 12:12 light–dark cycle, lights on at 0700 and free access to rodent pellets and tap water. Drugs were freshly prepared injected ip at 0800 and subjects were observed for 60min. When antagonists were used it was administered 15min before the agonist. Sprague–Dawley and taiep rats significantly increased their yawning frequency after systemic injection of (−)-quinpirole hydrochloride, R(+)-7-Hydroxy-2-(dipropylamino)tetralin hydrobromide (7-OH-DPAT) or trans-(±)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano [4,3-b]-1,4-oxazin-9-ol hydrochloride ((±)-PD 128,907). Among D2-like agonists used higher effects are obtained with (−)-quinpirole. The effects caused by (−)-quinpirole can be reduced by (−)-sulpiride; and yawning caused by 7-OH-DPAT was decreased by tiapride only in taiep rats. In Sprague–Dawley only (−)-sulpiride is able to decrease (−)-quinpirole-caused yawning. In conclusion, dopaminergic D2-like agonists are still able to cause yawning despite the severe myelin loss in taiep rats. Similarly, patients with various CNS illnesses that affect myelin, such as stroke or multiple sclerosis, are able to yawn suggesting that trigger neurons are still able to command this innate behavior.

Corticotropin-releasing factor antagonist reduces activation of noradrenalin and serotonin neurons in the locus coeruleus and dorsal raphe in the arousal response accompanied by yawning behavior in rats

We previously reported that intracerebroventricular (icv) administration of corticotropin-releasing factor (CRF) antagonist attenuates the arousal response during yawning behavior in rats. However, the CRF-related pathway involved in the arousal response during yawning is still unclear. In the present study, we assessed the involvement of the CRF-containing pathway from the hypothalamic paraventricular nucleus (PVN) to the locus coeruleus (LC) and the dorsal raphe nucleus (DRN) in the arousal response during frequent spontaneous yawning, which was induced by several microinjections of l-glutamate into the PVN in anesthetized rats, using c-Fos immunohistochemistry. The PVN stimulation showed significant increases in activation of PVN CRF neurons, LC noradrenalin (NA) neurons and DRN serotonin (5-HT) neurons as well as arousal response during yawning. But icv administration of a CRF receptor antagonist, α-helical CRF (9-41), significantly inhibited the activation of both LC NA neurons and DRN 5-HT neurons except the activation of CRF neurons in the PVN, and significantly suppressed the arousal response during yawning. These results suggest that the CRF-containing pathway from PVN CRF neurons to LC NA neurons and DRN 5-HT neurons can be involved in the arousal response during yawning behavior.

Orofacial dyskinesia monitored by telemetered electromyography in the rat, using yawning behaviour as a marker

Orofacial dyskinesia monitored by telemetered electromyography in the rat, using yawning behaviour as a marker

Identification of independent predictors for intravenous thiopental-induced yawning

To explore risk factors for the yawning response induced by the intravenous administration of thiopental during the induction of general anesthesia. We analyzed data from a cohort of 1322 patients who underwent elective surgery under general anesthesia plus intravenous thiopental. The data collected were: (a) the patients' demographic findings (age, sex, height, weight, cigarette smoking, hypertension, and presence of cerebral lesion), and (b) anesthesia-related findings (the kind of preanesthetic medication, i.e., atropine, epidural lidocaine, priming dose of vecuronium, fentanyl, and the dose of intravenous thiopental). An association between an individual variable in the evaluation model and the likelihood of thiopental-induced yawning behavior was characterized by means of the odds ratio. Multiple logistic regression was used to examine the independent contribution of each candidate variable, while controlling for all variables. After the intravenous administration of thiopental, 461 patients exhibited a yawning response. The probability of this response was decreased by the prior use of intravenous fentanyl, by female sex, and by premedication with clonidine, but the probability was unaffected by premedication with hydroxyzine, by the prior use of atropine, or by the presence of hypertension or a cerebral lesion. Thiopental-induced yawning may be suppressed by female sex, prior use of intravenous fentanyl, and premedication with clonidine. These findings may allow insights into the physiologic and pharmacological aspects of yawning in humans, thereby leading to the development methods to prevent thiopental-induced yawning.

Determination of in vivo dopamine D3 receptor selectivity for agonists and antagonists utilizing induction of yawning and hypothermia in rats

Accurate assessment of in vivo selectivity for preferential D3 agonists and antagonists has been slowed by the absence of behaviors specifically mediated by the D3 receptor as well as the relative lack of agonists and antagonists highly selective for the D3 receptor. We have previously demonstrated that the induction of yawning behavior by D2/D3 agonists is mediated by an agonist activity at the D3 receptor while the inhibition of yawning at higher doses results from a concomitant D2 agonist activity (Collins et al., 2005). In addition to the induction of yawning behavior, all D2/D3 agonists produce significant decreases in core body temperature, an effect that has been shown to be mediated by their D2 agonist activity (Chaperon et al., 2003). We have compared several dopaminergic agonists with a wide range of in vitro D3 selectivity, including; PD-128907, quinelorane, pramipexole, 7-OH-DPAT, quinpirole, apomorphine and sumanirole with respect to their ability to induce yawning behavior and hypothermia. In addition, the D2 antagonist, L-741626, and the D3 antagonists, U99194 and PG01037 have been used to pharmacologically validate the specific involvement of the D3 and D2 receptor in yawning and hypothermia respectively. Therefore, the induction and, at higher doses, suppression of yawning in conjunction with hypothermia allows the inference of an in vivo selectivity ratio for D3 compared to D2 receptor activity. Using this analysis, pramipexole is the most selective of the agonists tested, while apomorphine is the least. Supported by USPHS grants DA00254 and F013771 through NIDA.