Aspects Of Social Behavior Research Articles

Rescue of oxytocin response and social behaviour in a mouse model of autism.

One of the most fundamental challenges in developing treatments for autism-spectrum disorders is the heterogeneity of the condition. More than one hundred genetic mutations confer high risk for autism, with each individual mutation accounting for only a small fraction of autism cases1–3. Subsets of risk genes can be grouped into functionally-related pathways, most prominently synaptic proteins, translational regulation, and chromatin modifications. To possibly circumvent this genetic complexity, recent therapeutic strategies have focused on the neuropeptides oxytocin and vasopressin4–6 which regulate aspects of social behavior in mammals7. However, whether genetic risk factors might predispose to autism due to modification of oxytocinergic signaling remains largely unknown. Here, we report that an autism-associated mutation in the synaptic adhesion molecule neuroligin-3 (Nlgn3) results in impaired oxytocin signaling in dopaminergic neurons and in altered social novelty responses in mice. Surprisingly, loss of Nlgn3 is accompanied by a disruption of translation homeostasis in the ventral tegmental area. Treatment of Nlgn3KO mice with a novel, highly specific, brain-penetrant inhibitor of MAP-kinase interacting kinases resets mRNA translation and restores oxytocin and social novelty responses. Thus, this work identifies an unexpected convergence between the genetic autism risk factor Nlgn3, translational regulation, and oxytocinergic signaling. Focus on such common core plasticity elements might provide a pragmatic approach to reduce the heterogeneity of autism. Ultimately, this would allow for mechanism-based stratification of patient populations to increase the success of therapeutic interventions.

Functional magnetic resonance imaging multivoxel pattern analysis reveals neuronal substrates for collaboration and competition with myopic and predictive strategic reasoning.

Competition and collaboration are strategies that can be used to optimize the outcomes of social interactions. Research into the neuronal substrates underlying these aspects of social behavior has been limited due to the difficulty in distinguishing complex activation via univariate analysis. Therefore, we employed multivoxel pattern analysis of functional magnetic resonance imaging to reveal the neuronal activations underlying competitive and collaborative processes when the collaborator/opponent used myopic/predictive reasoning. Twenty‐four healthy subjects participated in 2 × 2 matrix‐based sequential‐move games. Searchlight‐based multivoxel patterns were used as input for a support vector machine using nested cross‐validation to distinguish game conditions, and identified voxels were validated via the regression of the behavioral data with bootstrapping. The left anterior insula (accuracy = 78.5%) was associated with competition, and middle frontal gyrus (75.1%) was associated with predictive reasoning. The inferior/superior parietal lobules (84.8%) and middle frontal gyrus (84.7%) were associated with competition, particularly in trials with a predictive opponent. The visual/motor areas were related to response time as a proxy for visual attention and task difficulty. Our results suggest that multivoxel patterns better represent the neuronal substrates underlying the social cognition of collaboration and competition intermixed with myopic and predictive reasoning than do univariate features.

Cultural dimensions, economic policy uncertainty, and momentum investing: international evidence

Culture, i.e. our values, norms, beliefs, and expected behaviors, has a significant influence on all aspects of social behavior. In addition, the economic policy-making of governments has been shown to have a significant impact on financial markets. In this paper, for the first time, we combine these two findings to examine whether, and if so how, culture and economic policy uncertainty have an impact on style investing, and more specifically on the popular momentum investing. We also extend previous studies in that we employ additional cultural dimensions, rather than just individualism, such as power distance, uncertainty avoidance, masculinity, and long-term orientation(Hofstede [1980]. Culture's Consequences: International Differences in Work-Related Values. Beverly Hills, CA: Sage, [1991]. Cultures and Organizations: Software of the Mind. London: McGraw-Hill, [2001]. Culture's Consequences. 2nd ed. Beverly Hills, CA: Sage, [2011]. “Dimensionalizing Cultures: The Hofstede Model in Context.” Online Readings in Psychology and Culture 2 (1): 1–26). Our results indicate a strong link between cultural dimensions, economic policy uncertainty, and momentum investing in international financial markets. We argue that this link is not affected by differences in the economic cycle, and/or global variables such as oil prices and global market-related uncertainty, and that apart from individualism, there are other cultural elements, which may influence momentum investing.

Ambient Temperature, Social Perception and Social Behavior

The literature suggests that human perception and behavior vary with physical temperature. We provide an experimental test of how different ambient temperature conditions impact social behavior and social perception: Subjects went through a series of tasks measuring various aspects of social behavior and perception under three temperature conditions (cold vs. optimal vs. warm). Despite well-established findings on temperature effects, our data suggest that physical temperature has no relevant influence on social behavior and social perception. We corroborate our finding of a null effect by the use of equivalence testing and provide a discussion in the light of recent failed replication attempts in this field of research.

R‐(‐)‐2,5‐dimethoxy‐4‐iodoamphetamine (DOI)‐induced Vocalizations and Observable Behavior in Nonhuman Primates

Many psychiatric disorders include elements of dysfunctional social behavior. Understanding the pharmacological underpinnings of social behavior in a nonhuman primate species that demonstrates a repertoire of complex behavior (e.g., aggression or affiliative behavior) may provide insights into novel medication approaches aimed at restoring social deficits. Specifically, squirrel monkeys (Samiri boliviensis) emit a rich array of vocalizations that provide information on socio‐emotional and behavioral states. These vocalizations often co‐occur with readily observable behaviors that are easily quantifiable, permitting analyses of various aspects of social behavior. Previous studies have indicated that affiliative, or prosocial, vocalizations (pulsed calls and chucks) and behavior (huddling) may be modulated by serotonin 2A (5HT2A) receptors. To begin to understand how 5HT2A receptor activation influences social behavior, we examined the effects of R‐(‐)‐2,5‐dimethoxy‐4‐iodoamphetamine (DOI), a potent and moderately selective 5HT2A agonist, on affiliative vocalizations and observable behavior in nonhuman primates. Pair‐housed squirrel monkeys (2 males, 2 females) were transferred to an observation chamber outside of the colony and vocalizations and huddling were recorded during test sessions. Saline or DOI (0.01 or 0.06 mg/kg, IM) was administered prior to 30 min sessions. Results show that vocalizations, in particular pulsed calls, were increased following administration of 0.01 mg/kg DOI (438 ± 28) relative to saline (190.5 ± 21.5); a higher dose of 0.06 mg/kg DOI elicited a number of vocalizations that were not different from saline (201.5 ± 88.5). Frequency of huddling was unaffected by saline or DOI administration, however, increases in general activity were observed following DOI administration at both doses in comparison to saline. A preliminary examination of potential sex differences suggests that there were no differences between males and females in huddling or total number of vocalizations, though males produced more alarm calls at the highest dose of DOI tested. These data suggest that 5HT2A receptor activation is sufficient for increasing affiliative vocalizations, but may not change other indices of prosocial behavior, such as huddling. Future studies will expand the list of behaviors captured to include positional analyses of each subject, as well as evaluating the contribution of other 5HT receptors to specific dimensions of prosocial behavior.Support or Funding InformationResearch support provided by R01DA048150 (SJK).

Developmental exposure to low levels of ethinylestradiol affects social play in juvenile male rats.

Juvenile social play contributes to the development of adult social and emotional skills in humans and non-human animals and is therefore a useful endpoint to study the effects of endocrine disrupters on behavior in animal models. Ethinylestradiol (EE2), a widely produced, powerful synthetic estrogen is widespread in the environment mainly because it is a component of the contraceptive pill. To understand whether clinical or environmental exposure to EE2 during critical perinatal periods can affect male social play, we exposed 72 male Sprague-Dawley rats to EE2 or vehicle either during gestation (from gestation day (GD) 5 through 20) or during lactation (from postnatal day (PND) 1 through 21). Two doses of EE2 were used to treat the dams: a lower dose in the range of possible environmental exposure (4ng/kg/day) and a higher dose similar to that received during contraceptive treatment (400ng/kg/day). Social play was observed between PND 40 and 45. A principal component analysis (PCA) of frequencies of behavioral items observed during play sessions allowed to allocate behaviors to the two main components that we named aggressive-like play and defensive-like play. Aggressive-like play was increased by gestational and decreased by lactational exposure. Defensive-like play was decreased by treatment. For both types of play the lower dose (4ng/kg/day) was as effective as the higher one. Total social activity was increased by gestational and decreased by lactational exposure. These findings provide further evidence that exposure to low and to very low doses of EE2 during critical periods of development can affect essential aspects of social behavior, and that the timing of exposure is critical to understand its developmental action.

Interpersonal Synchrony in Autism.

We review evidence for the presence, quality, and correlates of interpersonal synchrony in autism spectrum disorder (ASD) across four domains: motor, conversational, physiological, and neural. We also propose cognitive and neural mechanisms for the disruption of interpersonal synchrony and investigate synchrony as a mechanism of intervention in ASD. Across domains, synchrony is present but reduced or atypical in individuals with ASD during interactions with individuals with typical development (TD). Atypical synchrony may reflect the contribution of both intrapersonal mechanisms, such as atypical motor timing, and interpersonal mechanisms, such as atypical interindividual coupling. Research suggests evidence for synchrony interventions leading to improvements in some aspects of social behavior. Understanding synchrony in ASD has the potential to lead to biomarkers and interventions to support social functioning. However, further research should clarify mechanisms of atypical synchrony in ASD including taking features of the dyad into account.

Oxytocin as Treatment for Social Cognition, Not There Yet.

In a short time, oxytocin has progressed from being a regular hormone involved in parturition and breastfeeding to be possibly the neuromodulator that has gathered the most attention. Attributed many positive roles in the modulation of different aspects of social behavior, such as bonding, empathy, cooperation, trust, and generosity, as well as roles as a natural anxiolytic and antidepressant, the expectations on oxytocin becoming a treatment for a number of disorders with associated social deficits have dramatically raised over the last years. However, despite the field has been investigating oxytocin’s role in social behavior for over twenty years, there are still many unknowns on oxytocin’s mechanisms of action and efficiency and the increasing number of clinical trials administering oxytocin to different clinical groups seem to disagree in its properties and report in most cases conflicting results. This has led to some disappointment among researchers and clinicians as oxytocin might not be the miraculous molecule that works in a “one size fits all” fashion initially considered. Conversely, this down-side of oxytocin might merely reflect the complexity of its neurotransmission system. The current reality is that, although oxytocin seems to have potential therapeutic value, there are key questions that remain unanswered as to decide the optimal target groups and treatment course. Here, we present an overview on critical points regarding the oxytocin system in health and disease that need to be better understood to establish its therapeutic properties and to decide who could benefit the most from its treatment.

A framework for conceptualizing dimensions of social organization in mammals.

Mammalian societies represent many different types of social systems. While some aspects of social systems have been extensively studied, there is little consensus on how to conceptualize social organization across species. Here, we present a framework describing eight dimensions of social organization to capture its diversity across mammalian societies. The framework uses simple information that is clearly separated from the three other aspects of social systems: social structure, care system, and mating system. By applying our framework across 208 species of all mammalian taxa, we find a rich multidimensional landscape of social organization. Correlation analysis reveals that the dimensions have relatively high independence, suggesting that social systems are able to evolve different aspects of social behavior without being tied to particular traits. Applying a clustering algorithm allows us to identify the relative importance of key dimensions on patterns of social organization. Finally, mapping mating system onto these clusters shows that social organization represents a distinct aspect of social systems. In the future, this framework will aid reporting on important aspects of natural history in species and facilitate comparative analyses, which ultimately will provide the ability to generate new insights into the primary drivers of social patterns and evolution of sociality.

Vivir en las ciudades. Análisis de los atributos de migración y no migración en la jerarquía urbana para comprender algunos aspectos del comportamiento social en las ciudades peruanas

Utilizando los datos de la Encuesta Nacional de Hogares del Perú (2007, 2012 y 2017), exploramos dos canales de influencia de las migraciones internas sobre la sociabilidad y el comportamiento social urbano del periodo contemporáneo: el canal generacional (cohortes de nacimiento) y el canal de las estructuras y rasgos de los hogares. Asimismo, para comprender la ascendencia que al mismo tiempo tendría el grado de urbanización, utilizamos la clasificación del tamaño del centro poblado (jerarquía urbana) en interacción con una clasificación de migración interna (migrante, no migrante).

Disrupting the endocannabinoid system in early adolescence negatively impacts sociability

Animal models suggest that the endocannabinoid system (eCS) helps regulate various aspects of social behavior, including play behavior and social reward, during adolescence. Properly tuned endocannabinoid signaling may be a critical developmental component in the emergence of normal adult sociability. In the current experiment, we attempted to pharmacologically disrupt endocannabinoid tone during early adolescence, and then measure the behavioral effects at two subsequent time points. 36 male and 36 female Long Evans rats received daily injections of one of three treatments between post-natal day (PND) 25–39: 1) vehicle treatment, 2) 0.4 mg/kg CP55,940 (a potent CB1/CB2 receptor agonist), or 3) 0.5 mg/kg AM251 (a CB1 receptor antagonist/inverse agonist). Both soon after treatment (PND 40–44) and several weeks later (PND 66–70), subjects were tested in an elevated plus maze (EPM) for anxiety and in a three-chambered apparatus for sociability. For the latter test, the number of entries into each chamber and the amount of time spent investigating each target were measured. Analyses revealed significant main effects of both sex and age on sociability: males expressed greater sociability compared to females, and sociability was higher in adolescence than adulthood. Most importantly, drug treatment (both CP55,940 and AM251) attenuated sociability in adolescence without having a significant effect on anxiety in the EPM. However, this effect did not persist into adulthood. These results indicate that pharmacological disruption of endocannabinoid tone – through either chronic agonism or antagonism of cannabinoid receptors - during early adolescence has a detrimental effect on sociability. This effect may be caused by transient, compensatory alterations in the eCS.

About the inconvenience of handling mixed-breed herds; aspects of social behavior as a potential source of stress and economic losses.

The objective of this study was to assess aspects of the social behavior of a mixed-breed herd of beef cows as a potential source for stress and economic losses. Angus (AN; N = 10), Brahman (BR; N = 10), and Senepol (SE; N = 10) cows were assigned to two groups (N = 15 each containing equal breed numbers) on separate pastures. Agonistic interactions (win/loss) during feeding were recorded daily for 45days. Dominance values were estimated as the proportion of individuals dominated to total herdmates. From this, individuals were placed into social categories based upon linear ranking as follows: dominants (D), intermediate (I), and subordinates (S). Breed influenced (P < 0.01) social category, with SE cows being dominants (P < 0.05) over AN and BR cows. Interactions between AN and BR cows were less (P < 0.0005) than interactions between AN and SE (53 vs 140, respectively). Within breeds, BR (152) and SE (182) cows had more (P < 0.0005) agonistic interactions than AN (107) cows. Although apparently influenced by breed, agonistic interactions occurred more frequently (P < 0.005) between social categories than within social categories (814 vs 310, respectively). Dominant cows were involved in more agonistic interactions with cows from different social categories than were intermediate and subordinate cows (P < 0.0005). However, intermediate (100) and subordinate (157) cows generated more (P < 0.0005) agonistic interactions within their own social category than dominant cows (53). It was concluded that, in mixed-breed herds, breed influences both social organization and agonistic interactions which could be considered as potential sources of stress and economic losses.

Prenatal maternal stress effects on the development of primate social behavior

Prenatal developmental plasticity in response to various environmental and social adversities can affect multiple aspects of offspring phenotype including social behavior strategies with effects that can last into adulthood. Here, we (1) identify adaptive social behavior strategies and their underlying mechanisms as potential targets of developmental plasticity in primates, (2) derive predictions about social behavior outcomes of prenatal adversity from different types of evolutionary models, (3) review the primate evidence for prenatal stress effects on offspring cognitive function, social, and non-social behavior, and (4) discuss avenues for future research. The scarce evidence currently available points towards increased distress behavior, particularly in infant offspring, and reductions of activity, exploration, and affiliative behavior in response to experimental prenatal adversity. Not all effects are stable, the results do not replicate well, and, for the most part, the current data cannot be used to test predictions of evolutionary models because relevant aspects of social behavior were not quantified and not assessed in the complex social environments they evolved for. More comprehensive research in developmental plasticity needs to incorporate sex differences and the interaction of effects from different sensitive periods including adolescence. Moreover, future research needs to assess the role of social buffering in mediating intergenerational effects and trade-offs between the pace of life and social cognitive performance.

Spatial relationships among free-living cururos (Spalacopus cyanus) demonstrate burrow sharing and communal nesting

AbstractSpatial relationships among conspecifics can provide insights into numerous aspects of social behavior. Spatial data may be particularly important for characterizing the behavior of difficult-to-study species such as subterranean rodents, direct observations of which are challenging. To characterize the social organization of the cururo (Spalacopus cyanus), a subterranean species in the rodent family Octodontidae, we used radiotelemetry to quantify spatial relationships within populations of this species located in Parque Nacional Bosque Fray Jorge and Santuario de la Naturaleza Yerba Loca, Chile. Specifically, we sought to determine if adults in this diurnal species share burrows and subterranean nests, the two criteria typically used to identify subterranean rodents as social. Analyses of radio fixes collected during February–March 2003 revealed that cururos at both Fray Jorge and Yerba Loca shared nighttime nest sites; cluster analyses of these data identified multiple spatially distinct subsets of adults in each population. Overlap of minimum convex polygons constructed from radio fixes collected during daylight hours suggested burrow sharing by animals in both populations. Cluster analyses of overlap values revealed the same spatially distinct groups of individuals identified from analyses of nest sharing; in addition, these analyses revealed one cluster of animals in each population that was not evident from analyses of nighttime data. Collectively, these results confirm that cururos are social, with adults in both study populations sharing burrow systems and communal nests. Our findings add to the growing understanding of social organization in octodontid rodents and reveal a new system for comparative studies of the ecology and evolution of behavioral variation in burrow-dwelling mammals.

Social behavior and aging: A fly model.

The field of behavioral genetics has recently begun to explore the effect of age on social behaviors. Such studies are particularly important, as certain neuropsychiatric disorders with abnormal social interactions, like autism and schizophrenia, have been linked to older parents. Appropriate social interaction can also have a positive impact on longevity, and is associated with successful aging in humans. Currently, there are few genetic models for understanding the effect of aging on social behavior and its potential transgenerational inheritance. The fly is emerging as a powerful model for identifying the basic molecular mechanisms underlying neurological and neuropsychiatric disorders. In this review, we discuss these recent advancements, with a focus on how studies in Drosophila melanogaster have provided insight into the effect of aging on aspects of social behavior, including across generations.

Student Discipline Levels on School Rules and Their Implications in Guidance and Counseling

This research is based on a phenomenon that is still found by students who violate various rules and regulations in schools such as students who are not well-dressed, arrive late to school, absent without information and various other violations. This study aims to describe students' discipline towards school rules in terms of: (1) dressing, (2) timeliness, (3) social behavior, and (4) learning ethics. This type of research is descriptive. The research sample was 177 students at public Senior High School in Tanjung Mutiara, Agam Regency. The research findings revealed that students' discipline on aspects: (1) dressed as very high, (2) on aspects of timeliness classified as high, (3) on aspects of social behavior classified as high, and (4) on aspects of learning ethics classified as high.

Erroneous inference based on a lack of preference within one group: Autism, mice, and the social approach task.

The Social Approach Task is commonly used to identify sociability deficits when modeling liability factors for autism spectrum disorder (ASD) in mice. It was developed to expand upon existing assays to examine distinct aspects of social behavior in rodents and has become a standard component of mouse ASD-relevant phenotyping pipelines. However, there is variability in the statistical analysis and interpretation of results from this task. A common analytical approach is to conduct within-group comparisons only, and then interpret a difference in significance levels as if it were a group difference, without any direct comparison. As an efficient shorthand, we named this approach EWOCs: Erroneous Within-group Only Comparisons. Here, we examined the prevalence of EWOCs and used simulations to test whether this approach could produce misleading inferences. Our review of Social Approach studies of high-confidence ASD genes revealed 45% of papers sampled used only this analytical approach. Through simulations, we then demonstrate how a lack of significant difference within one group often does not correspond to a significant difference between groups, and show this erroneous interpretation increases the rate of false positives up to 25%. Finally, we define a simple solution: use an index, like a social preference score, with direct statistical comparisons between groups to identify significant differences. We also provide power calculations to guide sample size in future studies. Overall, elimination of EWOCs and adoption of direct comparisons should result in more accurate, reliable, and reproducible data interpretations from the Social Approach Task across ASD liability models. Autism Res 2019, 12: 1171-1183. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The Social Approach Task is widely used to assess social behavior in mice and is frequently used in studies modeling autism. However, reviewing published studies showed nearly half do not use correct comparisons to interpret these data. Using simulated and original data, we argue the correct statistical approach is a direct comparison of scores between groups. This simple solution should reduce false positives and improve consistency of results across studies.

Analytical validation of an Enzyme Immunoassay for the measurement of urinary oxytocin in dogs and wolves

Assessing changes in oxytocin (OT) levels in response to a variety of social stimuli has become of major interest in the field of behavioral endocrinology. OT is involved in the regulation of various aspects of social behavior such as tolerance, and the formation and maintenance of social bonds but also the regulation of stress. All of these aspects have been identified as potential targets of selection during the domestication process. Therefore, comparing the role of the oxytocinergic system in various aspects of dog and wolf social behavior, might help to understand whether this system was involved in the domestication process.Studies assessing OT levels in dogs and wolves have used invasively collected plasma and serum samples and non-invasively collected urine samples. However, when using an assay system on a new species a careful and complete validation of the method is of crucial importance, and to date no proper validation, to assess urinary OT levels in dogs and wolves, has been reported. We therefore conducted an analytical validation of an Enzyme Immunoassay (EIA) for the measurement of OT in urine of dogs and wolves, using a commercially available EIA. Stability tests revealed that OT levels degrade over time when stored at 4 °C, but are little affected by repeated thawing. In addition, our results indicate that the variance in OT levels is slightly lower when phosphoric acid is added following collection to prevent OT degradation. Long term storage tests revealed that urinary OT levels are least variable when stored as extracts in ethanol at −20 °C, rather than as unextracted urine samples. Validation results were acceptable with regard to parallelism, but values for accuracy and extraction efficiency were not meeting the standard criteria usually applied to steroid EIAs, especially when assessed for the lower range of the assay. The results of this study highlight the importance of an analytical assay validation, since even if validation parameters are not optimal, if published, they allow readers to estimate the relevance of studies using the validated method.

Social psychology, consumer culture and neoliberalism: A response to Phelps and White (2018)

AbstractThe following essay responds to three main issues raised by Phelps and White (2018) in their critical commentary on our article (McDonald, Gough, Wearing &amp; Deville, 2017). The first concerns the lack of precision in the conceptualisation of neoliberalism and the recent threats to it as we enter a potentially new phase of capitalism. While we share Phelps and White's concern, we argue that there is value in continuing to use neoliberalism as a concept for understanding some aspects of social behaviour. As to recent threats to neoliberalism, evidence indicates that it will continue to persist in the immediate future. To deal with neoliberalism's conceptual problems in social psychology, Phelps and White advance the potential theory of a ‘market‐derived logics’. We commend the authors for pursuing this endeavor, however, we caution that care needs to be taken in its conceptualisation. Lastly, we discuss Phelps and White's disciplinary reflections on social psychology.

Binding and Signaling Properties of the Leu8 and Pro8 Isoforms of Oxytocin at Vasopressin V1a Receptors from Primate Species Expressing Leu8 or Pro8 Oxytocin

Among New World monkeys, there is a remarkable correlation between multiple aspects of social behavior and their expression of an oxytocin (OT) variant with proline at the eighth position (Pro8OT) vs. the common mammalian OT ligand that has leucine at position 8 (Leu8OT). In light of evidence for OT involvement in normative and dysfunctional social behavior, a better understanding of the impact of OT ligand variation on receptor binding and signaling could provide insights into the pharmacological modulation of sociality. We previously showed that binding and calcium signaling at oxytocin receptors (OTRs) from four primate species were not different for Leu8 vs. Pro8 (Taylor JH et al., J Pharmacol Exp Ther, 367:101–107, 2018). OT also binds and activates vasopressin V1a receptors (V1aRs), whose preferred ligand is the closely related nonapeptide hormone arginine vasopressin (AVP). Thus the binding and signaling of Leu8OT and Pro8OT at V1aRs from Leu8OT‐ vs. Pro8OT‐expressing species was examined. V1aRs from marmoset (a Pro8OT species), macaque (a Leu8OT species), and human (a Leu8OT species) were expressed in CHO cells. Competition binding assays with intact cells on ice were performed using 125I‐OVTA. IC50 values in nM for Leu8OT, Pro8OT, and arginine vasopressin (AVP), respectively, were 220, 150, and 0.78 for marmoset; 28, 21, and 1.1 for macaque; and 16, 8, and 0.63 for human. Pro8OT thus has a slightly higher affinity than Leu8OT at all three receptors. Both OT isoforms exhibited about 20‐fold lower affinity than AVP for the macaque and human V1aRs but a nearly 200‐fold lower affinity for the marmoset V1aR. Calcium signaling downstream of V1aRs was assessed with FlexStation‐II assays. EC50 values in nM for Leu8OT, Pro8OT, and AVP, respectively, were 8.4, 6.7, and 0.06 for marmoset; 21, 10, and 0.03 for macaque; and 145, 110, and 2.1 for human. Thus the potency for Pro8OT is slightly higher than for Leu8OT, and the potencies for both OT isoforms are 50–100 times lower than for AVP, at all three V1aRs. These signaling potency differences are similar to the binding affinity differences for the OT isoforms at each receptor. The maximal calcium response to Leu8OT was about 80% of that for Pro8OT and AVP at the marmoset and macaque receptors; in contrast, the maximal Leu8OT and Pro8OT responses were only about 20% of the response to AVP for the human receptor, indicating that both OT isoforms are relatively weak partial agonists for the human V1aR. This difference in partial agonism at human V1aRs compared to marmoset and macaque V1aRs for both OT isoforms is intriguing. However, neither differences in V1aR ligand binding or calcium signaling provide an obvious explanation for the different behaviors of Pro8OT‐ versus Leu8OT‐expressing species, similar to our previous data showing minimal differences between the OT isoforms for binding and signaling at OTRs. Differential signaling to other downstream responses merits further investigation.Support or Funding InformationSupported by NIH grant 1‐R01‐HD089147 to JAF.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.