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Aggressive behavior in dogs poses public health and animal welfare concerns, however the biological mechanisms regulating dog aggression are not well understood. We investigated the relationships between endogenous plasma oxytocin (OT) and vasopressin (AVP)—neuropeptides that have been linked to affiliative and aggressive behavior in other mammalia...
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Aggression in group-housed laboratory mice is a serious animal welfare concern. Further understanding of the causes of mouse aggression could have a significant impact on a large number of laboratory animals. The NC3Rs led a crowdsourcing project to collect data on the prevalence and potential triggers of aggression in laboratory mice. The crowdsou...
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... amygdala, nucleus accumbens, hypothalamus), as these areas are responsible for emotional arousal and responses to dangerous and threatening stimuli [2,7]. Within these regions, neuropeptides such as oxytocin (OXT) and arginine vasopressin (AVP) are involved in regulating social behaviour, including aggression [8][9][10]. The corticolimbic system has been extensively studied in rodents to shed light on the role of these neuropeptides in aggressive behaviour [5,11,12]. ...
Aggression and its neurochemical modulators are typically studied in males, leaving the mechanisms of female competitive aggression or dominance largely unexplored. To better understand how competitive aggression is regulated in the primate brain, we used receptor autoradiography to compare the neural distributions of oxytocin and vasopressin receptors in male and female members of female-dominant versus egalitarian/codominant species within the Eulemur genus, wherein dominance structure is a reliable proxy of aggression in both sexes. We found that oxytocin receptor binding in the central amygdala (CeA) was predicted by dominance structure, with the members of three codominant species showing more oxytocin receptor binding in this region than their peers in four female-dominant species. Thus, both sexes in female-dominant Eulemur show a pattern consistent with the regulation of aggression in male rodents. We suggest that derived pacifism in Eulemur stems from selective suppression of ancestral female aggression over evolutionary time via a mechanism of increased oxytocin receptor binding in the CeA, rather than from augmented male aggression. This interpretation implies fitness costs to female aggression and/or benefits to its inhibition. These data establish Eulemur as a robust model for examining neural correlates of male and female competitive aggression, potentially providing novel insights into female dominance.
... Conversely, serum corticosterone and AVP showed positive correlations with aggression duration, suggesting that these markers may facilitate or exacerbate aggressive tendencies. The role of AVP in promoting aggression has been well-documented, with AVP acting as a neuromodulator in aggression-related brain areas [64,65]. For Table 8 Impact of housing condition and aggressive behaviour duration on brain neurochemical marker expression instance, Ferris et al. (1984) demonstrated that vasopressin injections into the hypothalamus could trigger aggressive behaviours in golden hamsters, marking one of the first studies to establish this relationship [66]. ...
Background
Sexual violence, a pervasive global issue, significantly impacts individuals and societies, necessitating a deeper understanding of its underlying biological mechanisms. This study aimed to elucidate the role of stress-induced dysregulation of the hypothalamus-pituitary-adrenocortical axis in sexual aggression in male Wistar rats. Employing a sexual aggression paradigm, we investigated the effects of social isolation on aggression, anxiety-like behaviour, and neurochemistry in virgin adult male Wistar rats.
Results
The results showed that social isolation significantly escalated aggressive behaviours and induced anxiety-like responses in male rats. The sexual aggression test revealed that socially isolated males exhibited heightened aggression towards non-receptive females. Neurochemical analyses indicated significant alterations in key markers, such as corticotrophin-releasing hormone, oxytocin, and arginine vasopressin, correlating with the observed behavioural changes. Gene expression analyses revealed significant findings, particularly in the expression of the oxytocin receptor (OXTR) and vasopressin receptor 1 A (AVPR1A) genes. Social isolation and the duration of aggressive behaviour prior to the sexual aggression test significantly influenced OXTR expression in the hippocampus and AVPR1A expression in both the prefrontal cortex and hippocampus, highlighting the complex interplay between environmental stressors, neurochemical responses, and gene expression in the manifestation of sexual aggression behaviour.
Conclusions
This study underscores the critical impact of stress and social isolation on sexual aggression, providing valuable insights into possible neurobiological underpinnings of sexual violence. Understanding these mechanisms is crucial for developing effective interventions to mitigate the consequences of sexual aggression.
... Arginine Vasopressin (AVP) levels correlate with specific behavioural patterns in dogs: higher plasma AVP has been associated with increased aggression towards other dogs (MacLean et al., 2017b), while salivary AVP increased in dogs lacking human interaction during human-animal interaction social studies (MacLean et al., 2017). Though AVP responds to acute stress (Kooriyama and Ogata (2021) and could provide insights into both stress states and aggressive predispositions, research has not yet examined effects of age, body weight, sex or reproductive status. ...
This paper aims to initiate new conversations about the use of physiological indicators when assessing the welfare of dogs. There are significant concerns about construct validity - whether the measures used accurately reflect welfare. The goal is to provide recommendations for future inquiry and encourage debate. We acknowledge that the scientific understanding of animal welfare has evolved and bring attention to the shortcomings of commonly used biomarkers like cortisol. These indicators are frequently used in isolation and with limited salient dog descriptors, so fail to reflect the canine experience adequately. Using a systems approach, we explore various physiological systems and alternative indicators, such as heart rate variability and oxidative stress, to address this limitation. It is essential to consider factors like age, body weight, breed, and sex when interpreting these biomarkers correctly, and researchers should report on these in their studies. This discussion identifies possible indicators for both positive and negative experiences. In conclusion, we advocate for a practical, evidence-based approach to assessing indicators of canine welfare, including non-invasive collection methods. We acknowledge the complexity of evaluating experiential responses in dogs across different situations and the need for continued work to improve practices and refine terminology. This will enhance our ability to accurately understand welfare and improve the wellbeing of dogs, serving to inform standards of animal welfare assessment. We hope this will promote more fundamental research in canine physiology to improve construct validity, leading to better practices, ultimately improving the lives of dogs.
... Nevertheless, the topic of aggression is very complex, as it should always be noted that there are different types of aggression (like, e.g., defensive or status-related aggression) [26][27][28][29][32][33][34][35]. However, it is not just hormones that play a decisive role in the occurrence of certain forms of aggression. ...
Simple Summary
Neutering is one of the most common procedures for dogs worldwide. While motivations for neutering vary, this procedure is often chosen with the hope of addressing undesirable behaviours in male dogs. In our study, 230 mixed-breed dogs (115 neutered and 115 intact) were examined. The dogs were categorised as “small”, “medium”, “large”, and “giant”. An online questionnaire was used, which asked about certain behavioural characteristics on the one hand and personality on the other. The results showed that neutered dogs appeared more stressed and aggressive than intact dogs. In addition, neutered small, medium, and large dogs were more stressed than giant dogs. Neutered dogs were also less social, trainable, emotionally calm and extroverted than intact dogs. This all suggests that neutering should be questioned and decided on an individual basis, as hormonal changes can have a considerable influence on dog behaviour.
Abstract
This study investigates the behavioural differences between neutered and intact dogs. A total of 230 questionnaires of neutered (n = 115) and intact (n = 115) mixed-breed male dogs were collected. Small, medium, large, and giant dogs were analysed to investigate a possible influence of body size. The results showed neuters were significantly more stressed than intacts (multinomial logistic regression, p = 0.001). In terms of stress by influences (such as separation anxiety and anxiety at car rides), neutered small, medium, and large dogs were more stressed than giant dogs (multinomial logistic regression, p = 0.05). Neuters were also found to be more aggressive in general (multinomial logistic regression, p = 0.04) and more aggressive on the walk (multinomial logistic regression, p = 0.02). In addition, personality questionnaires revealed significant differences in all characteristics. Neuters were less emotionally calm (multiple ordinal regression, p = 0.03), less trainable and less sociable (each multiple ordinal regression, p < 0.001). They also scored lower on extraversion (multiple ordinal regression, p = 0.04). These findings highlight the importance of further research into the behavioural effects of neutering dogs, as well as the need for evidence-based guidelines for neutering practices.
... AVP is the primary activator of the HPA axis and a vasoconstrictor as well as an antidiuretic that is also being actively studied as a stress biomarker. 56,57 Additionally, AVP has a behavioral role and is a neural regulator of numerous social behaviors, including affiliation, aggression, and pair bonding. 58 De Kloet et al. previously identified an elevated concentration of plasma AVP in human patients with post-traumatic stress disorder compared to both traumatized and healthy non-traumatized controls. ...
Numerous studies have reported that physical or emotional stress can provoke atrial fibrillation (AF) or vice versa, which suggests a potential link between exposure to external stressors and AF. This review article sought to describe in detail the relationship between major stress biomarkers and the pathogenesis of AF and presents up-to-date knowledge on the role of physiological and psychological stress in AF patients. For this purpose, this review article contends that plasma cortisol is linked to a greater risk of AF. A previous study has investigated the association between increased copeptin levels and paroxysmal AF (PAF) in rheumatic mitral stenosis and reported that copeptin concentration was not independently associated with AF duration. Reduced levels of chromogranin were measured in patients with AF. Furthermore, the dynamic activity of antioxidant enzymes, including catalase as well as superoxide dismutase, was examined in PAF patients during a period of <48 h. Malondialdehyde activity, serum high-sensitivity C-reactive protein, and high mobility group box 1 protein concentrations were significantly greater in patients with persistent AF or PAF compared to controls. Pooled data from 13 studies confirmed a significant reduction in the risk of AF related to the administration of vasopressin. Other studies have revealed the mechanism of action of heat shock proteins (HSPs) in preventing AF and also discussed the therapeutic potential of HSP-inducing compounds in clinical AF. More research is required to detect other biomarkers of stress, which have not been reported in the pathogenesis of AF. Further studies are required to identify their mechanism of action and drugs to manage these biomarkers of stress in AF patients, which might help to reduce the prevalence of AF globally.
... No studies have been published about salivary CoP concentrations, despite the ever-increasing literature regarding this biomarker's levels in serum. However, CoP is cleaved from the neurohypophysial hormone prepro-vasopressin and secreted in the blood during procession to vasopressin, whose time to reach saliva is quite well understood, appearing faster than other salivary hormones (e.g., cortisol) [22]. Previous studies have shown effects at a minimum time delay of 10 min [22,37] while other studies suggested that increases in salivary concentrations may be even earlier (e.g., 3 min) [38]. ...
... However, CoP is cleaved from the neurohypophysial hormone prepro-vasopressin and secreted in the blood during procession to vasopressin, whose time to reach saliva is quite well understood, appearing faster than other salivary hormones (e.g., cortisol) [22]. Previous studies have shown effects at a minimum time delay of 10 min [22,37] while other studies suggested that increases in salivary concentrations may be even earlier (e.g., 3 min) [38]. Given that stressors induce a rise in copeptin levels which, although non-specific, is proportional to their magnitude [39], it is possible that, in our study, the non-significant rise observed in salivary CoP at T1 reflected a successful coping response in Control dogs elicited at the start of the experiment in a novel environment. ...
Simple Summary
Up to 56% of the general dog population show signs of separation-related problems, a group of problems characterized by highly variable phenotypes on which research, to date, has mostly provided contradictory findings. In the present study, we analyzed the behavior and salivary concentrations of copeptin, a biologically stable biomarker of stress, in dogs with separation distress and in dogs with no problems. The animals were tested before, during and after three-minute separation from the owner, in a new environment. Dogs in the two groups differed significantly in their activity levels and stress-relief activities during the three observation phases. In addition, a different tendency in the two groups was found in salivary copeptin concentration behavior.
Abstract
The need for faster diagnosis and more accurate treatment decisions in separation-related problems (SRPs) in dogs is urgent, and a more precise behavioral phenotyping and the development of biomarkers may be of great value. Vasopressin could be a potential non-invasive biomarker of anxiety in dogs with SRPs, but reliable measurement of its concentration is challenging. Here, we compared the behavior and salivary concentrations of copeptin, an arginine vasopressin surrogate, in dogs with SRPs (Case group, n = 13) and with no problems (Control group, n = 15) as they were introduced to a novel environment and subjected to a short episode of separation and reunion with the owner. Dogs in the Case group had greater odds of showing locomotory or oral behaviors during the pre- and post-separation than Controls, while the odds were significantly lower during separation. They also had greater odds of being persistent in seeking attention and proximity from the stranger during reunion. Overall, dogs with SRPs were more likely to express an anxiety-like state during the entire test than Controls, with separation from the owner, and even its anticipation, possibly accounting for this group difference. Although salivary copeptin concentrations did not differ between the two groups, a different trend was detected in Cases and Controls that is worth exploring in further validation studies involving a larger sample.
... Validation of this assay for serum was not performed in this study and should be considered a limitation. However, ELISA measurement of blood and saliva AVP has been recently validated in two studies assessing canine patients and proves to be a reliable way of measuring AVP (MacLean et al., 2017(MacLean et al., , 2018. The measurement of AVP using ELISA assays has become more common in several species as it does not require radioisotopes (Leng & Sabatier, 2016 In conclusion, intravenous ondansetron displays linear pharmacokinetics at the dosage protocols used in this study despite being evaluated in a mixed group of dogs with varying disease processes. ...
The purpose of this study was to evaluate the pharmacokinetics of intravenous (IV) ondansetron in a population of hospitalized dogs exhibiting clinical signs of nausea. The causes of nausea included pancreatitis, gastroenteritis, endocarditis, chemotherapy‐induced nausea, diabetes mellitus and ketoacidosis, acute kidney injury with aspiration pneumonia, pyometra, uroabdomen, neoplasia, and hepatopathy. Twenty‐four dogs were randomly assigned to one of the following IV ondansetron protocols: 1 mg/kg q12h, 0.5 mg/kg q12h, 1 mg/kg q8h, 0.5 mg/kg q8h. Serum was collected at 0, 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after the first dose, and nausea scores were recorded at multiple time points. Ondansetron and arginine vasopressin (AVP) concentrations were measured via high‐performance liquid chromatography coupled to tandem mass spectrometry and ELISA, respectively. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Ondansetron displayed linear pharmacokinetics. In the 0.5 mg/kg group, mean Cmax = 214 ng/ml, AUC0–8h = 463 ng/ml*h, and calculated half‐life was 1.9 h. In the 1 mg/kg group, mean Cmax = 541 ng/ml, AUC0–8h = 1057 ng/ml*h and calculated half‐life was 1.6 h. Serum ondansetron concentrations were not significantly different between dogs that required rescue anti‐nausea medication (non‐responders) and dogs that did not require rescue therapy (responders). In total, 83.3% of patients in the 0.5 mg/kg q8h, 0.5 mg/kg q12h, and 1 mg/kg q8h groups had improvement in nausea scores. In total, 66.7% of patients in the 1 mg/kg q12h group had improvement in nausea scores. In total, 33% of patients had resolution of nausea in the 0.5 mg/kg q8h, 1 mg/kg q8h, and 1 mg/kg q12h groups, and 16% of patients had resolution of nausea in the 0.5 mg/kg q12h group. AVP concentrations were highly variable and did not correlate with nausea scores. Nausea scores significantly decreased regardless of dosage protocol. AVP was not a reliable biomarker of nausea in this group of dogs.
... Like OXT signaling, AVP signaling has also been linked to altered levels of aggression; however, the impact of AVP on aggression is more mixed. While increased AVP signaling has been associated with an increase in aggressive behaviors in both hamsters and dogs (Ferris et al., 1997;MacLean et al., 2017), decreased AVP signaling has alternatively been shown to be required for the development of aggressive behaviors in a female rat model of enhanced aggression . One potential explanation for these contrasting results is that the impact of AVP may be region-specific. ...
Disorders involving hypothalamic and pituitary (HPIT) structures—including craniopharyngioma, Langerhans cell histiocytosis, and intracranial germ cell tumors—can disrupt brain and endocrine function. An area of emerging clinical concern in patients with these disorders is the co-occurring socio-behavioral dysfunction that persists after standard hormone replacement therapy. Although the two neuropeptides most implicated in mammalian social functioning (oxytocin and arginine vasopressin) are of hypothalamic origin, little is known about how disease-induced damage to HPIT structures may disrupt neuropeptide signaling and, in turn, impact patients’ socio-behavioral functioning. Here we provide a clinical primer on disorders of HPIT involvement and a review of neuropeptide signaling and socio-behavioral functioning in relevant animal models and patient populations. This collective evidence suggests that neuropeptide signaling disruptions contribute to socio-behavioral deficits experienced by patients with disorders of HPIT involvement. A better understanding of the biological underpinnings of patients’ socio-behavioral symptoms is now needed to enable the development of the first targeted pharmacological strategies by which to manage patients’ socio-behavioral dysfunction.
... Similar observations regarding the spaying procedure on females were presented by Starling et al. [99]. On the other hand, Farhoody et al. [104] showed the opposite phenomenon, wherein dogs subjected to gonadectomy there was a slight but statistically significant increase in the probability of aggression in relation to unknown persons, without in any way affecting the risk of aggression towards people and dogs they know. ...
Simple Summary
Aggression in dogs is often a reason for abandonment and/or euthanasia. Recently, knowledge about aggression has been subjected to more detailed analysis. In recent years, it has been studied in terms of factors affecting it, such as diet (especially nutritional supplements) and physiology (endocrine system). In addition, recently, new methods of brain research, such as neurocognitive research, have appeared, which enable a significant increase in knowledge about dog behavior, including aggression.
Abstract
Aggression as a behavior is not always desirable, often ends in abandonment and/or euthanasia. However, it is possible to prevent the occurrence of unwanted aggression in domestic dogs. Aggression is not a fully understood phenomenon. In recent years, many studies have focused on the influence of diet and physiology (including the endocrine system) on the emergence of behavioral disorders. In particular, the emphasis was put on nutritional additives such as fatty acids, amino acids, and probiotics. In addition, the possibility of using neurocognition in the observation of abnormal behavior in dogs has also been discussed, which may allow for a more detailed determination of the basis of aggressive behavior in dogs. In this review, the concepts related to aggression and its potential causes have been gathered. In addition, the possible influence of diet and hormones on aggression in dogs has been discussed, as well as the application of neurocognition in the possibility of its diagnosis.
... Relative to oxytocin, there has been comparatively little focus on the roles of vasopressin in domestication, but we hypothesize that functional changes involving vasopressin have also been important for changes to stress physiology, selective sociality, and aggression across the course of domestication. Notably, in initial studies on neuropeptides and aggression in dogs, aggressive behavior has been linked to circulating vasopressin, but not oxytocin concentrations [136]. ...
The process of dog domestication likely involved at least two functional stages. The initial stage occurred when subpopulations of wolves became synanthropes, benefiting from life nearby or in human environments. The second phase was characterized by the evolution of novel forms of interspecific cooperation and social relationships between humans and dogs. Here, we discuss possible roles of the oxytocin system across these functional stages of domestication. We hypothesize that in early domestication, oxytocin played important roles in attenuating fear and stress associated with human contact. In later domestication, we hypothesize that oxytocin's most critical functions were those associated with affiliative social behavior, social engagement, and cooperation with humans. We outline possible neurobiological changes associated with these processes and present a Siberian fox model of canid domestication in which these predictions can be tested. Lastly, we identify limitations of current studies on the neuroendocrinology of domestication and discuss challenges and opportunities for future research.
