Query: oxytocin

title: Lost connections: Oxytocin and the neural, physiological, and behavioral consequences of disrupted relationships.
abstract: In humans and rodent animal models, the brain oxytocin system is paramount for facilitating social bonds, from the formation and consequences of early life parent infant bonds to adult pair bond relationships. In social species, oxytocin also mediates the positive effects of healthy social bonds on the partners' well being. However, new evidence suggests that the negative consequences of early neglect or partner loss may be mediated by disruptions in the oxytocin system as well. With a focus on oxytocin and its receptor, we review studies from humans and animal models, i.e. mainly from the biparental, socially monogamous prairie vole (Microtus ochrogaster) on the beneficial effects of positive social relationships both between offspring and parents and in adult partners. The abundance of social bonds and benevolent social relationships, in general, are associated with protective effects against psycho and physiopathology not only in the developing infant, but also during adulthood. Furthermore, we discuss the negative effects on well being, emotionality and behavior, when these bonds are diminished in quality or are disrupted, for example through parental neglect of the young or the loss of the partner in adulthood. Strikingly, in prairie voles, oxytocinergic signaling plays an important developmental role in the ability to form bonds later in life in the face of early life neglect, while disruption of oxytocin signaling following partner loss results in the emergence of depressive like behavior and physiology. This review demonstrates the translational value of animal models for investigating the oxytocinergic mechanisms that underlie the detrimental effects of developmental parental neglect and pair bond disruption, encouraging future translationally relevant studies on this topic that is so central to our daily lives.

title: Complementary Neural Circuits for Divergent Effects of Oxytocin: Social Approach Versus Social Anxiety
abstract: Oxytocin (OT) is widely known for promoting social interactions, but there is growing appreciation that it can sometimes induce avoidance of social contexts. The social salience hypothesis posed an innovative solution to these apparently opposing actions by proposing that OT enhances the salience of both positive and negative social interactions. The mesolimbic dopamine system was put forth as a likely system to evaluate social salience owing to its well described role in motivation. Evidence from several sources supports the premise that OT acting within the nucleus accumbens and ventral tegmental area facilitates social reward and approach behavior. However, in aversive social contexts, additional pathways play critical roles in mediating the effects of OT. Recent data indicate that OT acts in the bed nucleus of the stria terminalis to induce avoidance of potentially dangerous social contexts. Here, we review evidence for neural circuits mediating the effects of OT in appetitive and aversive social contexts. Specifically, we propose that distinct but potentially overlapping circuits mediate OT dependent social approach or social avoidance. We conclude that a broader and more inclusive consideration of neural circuits of social approach and avoidance is needed as the field continues to evaluate the potential of OT based therapeutics.

title: Cross talk among oxytocin and arginine vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery
abstract: Oxytocin (OT) and arginine vasopressin (AVP) act in the brain to regulate social cognition/social behavior and in the periphery to influence a variety of physiological processes. Although the chemical structures of OT and AVP as well as their receptors are quite similar, OT and AVP can have distinct or even opposing actions. Here, we review the increasing body of evidence that exogenously administered and endogenously released OT and AVP can activate each other's canonical receptors (i.e. cross talk) and examine the possibility that receptor cross talk following the synaptic and non synaptic release of OT and AVP contributes to their distinct roles in the brain and periphery. Understanding the consequences of cross talk between OT and AVP receptors will be important in identifying how these peptides control social cognition and behavior and for the development of drugs to treat a variety of psychiatric disorders.

title: Oxytocin modulates social value representations in the amygdala
abstract: Humans exhibit considerable variation in how they value their own interest relative to the interests of others. Deciphering the neural codes representing potential rewards for self and others is crucial for understanding social decision making. Here we integrate computational modeling with functional magnetic resonance imaging to investigate the neural representation of social value and the modulation by oxytocin, a nine amino acid neuropeptide, in participants evaluating monetary allocations to self and other (self other allocations) We found that an individual's preferred self other allocation serves as a reference point for computing the value of potential self other allocations. In more prosocial participants, amygdala activity encoded a social value distance signal; that is, the value dissimilarity between potential and preferred allocations. Intranasal oxytocin administration amplified this amygdala representation and increased prosocial behavior in more individualistic participants but not in more prosocial ones. Our results reveal a neurocomputational mechanism underlying social value representations and suggest that oxytocin may promote prosociality by modulating social value representations in the amygdala.Using a behaviorally obtained reference point to compute social value, Ma et al. show that social value distance is encoded by the amygdala in prosocials. Oxytocin amplifies this amygdala representation and increases prosociality in individualists.

title: Oxytocin and vasopressin in the rodent hippocampus
abstract: The role of the hippocampus in social memory and behavior is under intense investigation. Oxytocin (Oxt) and vasopressin (Avp) are two neuropeptides with many central actions related to social cognition. Oxt and Avp expressing fibers are abundant in the hippocampus and receptors for both peptides are seen throughout the different subfields, suggesting that Oxt and Avp modulate hippocampal dependent processes. In this review, we first focus on the anatomical sources of Oxt and Avp input to the hippocampus and consider the distribution of their corresponding receptors in different hippocampal subfields and neuronal populations. We next discuss the behavioral outcomes related to social memory seen with perturbation of hippocampal Oxt and Avp signaling. Finally, we review Oxt and Avp modulatory mechanisms in the hippocampus that may underlie the behavioral roles for both peptides.

title: The Social Salience Hypothesis of Oxytocin
abstract: Oxytocin is a nonapeptide that also serves as a neuromodulator in the human central nervous system. Over the last decade, a sizeable body of literature has examined its effects on social behavior in humans. These studies show that oxytocin modulates various aspects of social behaviors such as empathy, trust, in group preference, and memory of socially relevant cues. Several theoretical formulations have attempted to explain the effects of oxytocin. The prosocial account argues that oxytocin mainly enhances affiliative prosocial behaviors; the fear/stress theory suggests that oxytocin affects social performance by attenuating stress; and the in /out group approach proposes that oxytocin regulates cooperation and conflict among humans in the context of intergroup relations. Nonetheless, accumulating evidence reveals that the effects of oxytocin are dependent on a variety of contextual aspects and the individual's characteristics and can induce antisocial effects including aggression and envy. In an attempt to reconcile these accounts, we suggest a theoretical framework that focuses on the overarching role of oxytocin in regulating the salience of social cues through its interaction with the dopaminergic system. Crucially, the salience effect modulates attention orienting responses to external contextual social cues (e.g. competitive vs. cooperative environment) but is dependent on baseline individual differences such as gender, personality traits, and degree of psychopathology. This view could have important implications for the therapeutic applications of oxytocin in conditions characterized with aberrant social behavior.

title: Intranasal Oxytocin: Myths and Delusions
abstract: Despite widespread reports that intranasal application of oxytocin has a variety of behavioral effects, very little of the huge amounts applied intranasally appears to reach the cerebrospinal fluid. However, peripheral concentrations are increased to supraphysiologic levels, with likely effects on diverse targets including the gastrointestinal tract, heart, and reproductive tract. The wish to believe in the effectiveness of intranasal oxytocin appears to be widespread and needs to be guarded against with scepticism and rigor. Preregistering trials, declaring primary and secondary outcomes in advance, specifying the statistical methods to be applied, and making all data openly available should minimize problems of publication bias and questionable post hoc analyses. Effects of intranasal oxytocin also need proper dose response studies, and such studies need to include control subjects for peripheral effects, by administering oxytocin peripherally and by blocking peripheral actions with antagonists. Reports in the literature of oxytocin measurements include many that have been made with discredited methodology. Claims that peripheral measurements of oxytocin reflect central release are questionable at best.

title: Oxytocin Receptors in the Anteromedial Bed Nucleus of the Stria Terminalis Promote Stress Induced Social Avoidance in Female California Mice
abstract: The neuropeptide oxytocin (OT) is a key regulator of social and emotional behaviors. The effects of OT are context dependent, and it has been proposed that OT increases the salience of both positive and negative social cues. Here we tested whether the bed nucleus of the stria terminalis (BNST) mediates anxiogenic effects of OT.  First, we studied the effects of systemic administration of an OT receptor (OTR) antagonist L 368,899 on social behavior in male and female California mice exposed to social defeat. We examined the effect of L 368,899 on G protein activation and used early growth response factor 1 immunohistochemistry to identify potential sites of OTR action. Finally, we examined the effects of L 368,899 infused in the BNST on behavior.  A single dose of systemic L 368,899 increased social approach in stressed female mice and decreased social approach in male mice naive to defeat. L 368,899 prevented OT activation of G proteins and did not activate G proteins in the absence of OT. Intranasal OT, which reduces social approach in female mice but not male mice, increased early growth response factor 1 immunoreactivity in the nucleus accumbens core and anteromedial BNST in female mice but not in male mice. Stressed female mice that received an infusion of L 368,899 into the anteromedial BNST but not the nucleus accumbens core increased social approach and decreased social vigilance responses.  Our results suggest that OTR activation in anteromedial BNST induces a vigilance response in which individuals avoid, yet attend to, unfamiliar social contexts. Our results suggest that OTR antagonists may have unappreciated therapeutic potential for stress induced psychiatric disorders.

title: Oxytocin enhances the pain relieving effects of social support in romantic couples
abstract: Social support plays a vital role in physical and mental well being. The neuropeptide hormone oxytocin (OXT) has been implicated in modulating pair bonding and affiliative behaviors, but whether OXT contributes to the analgesic effects of a romantic partner's touch remains elusive. In the present randomized placebo controlled, between group, functional magnetic resonance imaging study involving 194 healthy volunteers (97 heterosexual couples) we tested the effects of intranasal OXT (24 IU) on handholding as a common mode of expressing emotional support in romantic couples. We scanned the subjects while brief electric shocks were administered. The subjects assumed that they received social support from either their romantic partner or an unfamiliar person. Unbeknown to the subject, in the partner and stranger support conditions, the same male experimenter always held the subject's left hand. Partner support was most effective in reducing the unpleasantness of electric shocks, and OXT further attenuated the unpleasantness across conditions. On the neural level, OXT significantly augmented the beneficial effects of partner support, as evidenced by a stronger decrease of neural responses to shocks in the anterior insula (AI) a stronger activity increase in the middle frontal gyrus (MFG) and a strengthened functional coupling between the AI and MFG. Our results support the notion that OXT specifically modulates the beneficial effects of social support in romantic couples by concomitantly reducing pain associated activity and increasing activity linked to cognitive control and pain inhibition. We hypothesize that impaired OXT signaling may contribute to the experience of a lack of partner support.

title: Oxytocin increases trust in humans
abstract: Trust pervades human societies. Trust is indispensable in friendship, love, families and organizations, and plays a key role in economic exchange and politics. In the absence of trust among trading partners, market transactions break down. In the absence of trust in a country's institutions and leaders, political legitimacy breaks down. Much recent evidence indicates that trust contributes to economic, political and social success. Little is known, however, about the biological basis of trust among humans. Here we show that intranasal administration of oxytocin, a neuropeptide that plays a key role in social attachment and affiliation in non human mammals, causes a substantial increase in trust among humans, thereby greatly increasing the benefits from social interactions. We also show that the effect of oxytocin on trust is not due to a general increase in the readiness to bear risks. On the contrary, oxytocin specifically affects an individual's willingness to accept social risks arising through interpersonal interactions. These results concur with animal research suggesting an essential role for oxytocin as a biological basis of prosocial approach behaviour.