Oxytocin and social cognition in rhesus macaques: Implications for understanding and treating human psychopathology

Chang, Steve; Platt, Michael L.

doi:10.1016/j.brainres.2013.11.006

Cited by 61 publications

(55 citation statements)

References 114 publications

(168 reference statements)

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“…Additionally, the supralinear effects of OTNAL cannot be explained by a nonspecific increase in arousal, because the total count of fixations in the OTNAL condition was, in fact, not higher than in the SAL, NAL, or OT conditions (all P > 0.05, one-way ANOVA with Tukey-Kramer post hoc tests). Finally, in reference to previous literature documenting the effects of OT in social attention (33,34), OT overall increased fixations to the eyes compared with SAL in this real-life dyadic setting [ Fig. 1E; t(19) = 1.63, P = 0.059, paired-sample t test], although the effect was marginal.…”

Section: Resultssupporting

confidence: 66%

Oxytocin under opioid antagonism leads to supralinear enhancement of social attention

Monte

Piva

Anderson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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To provide new preclinical evidence toward improving the efficacy of oxytocin (OT) in treating social dysfunction, we tested the benefit of administering OT under simultaneously induced opioid antagonism during dyadic gaze interactions in monkeys. OT coadministered with a μ-opioid receptor antagonist, naloxone, invoked a supralinear enhancement of prolonged and selective social attention, producing a stronger effect than the summed effects of each administered separately. These effects were consistently observed when averaging over entire sessions, as well as specifically following events of particular social importance, including mutual eye contact and mutual reward receipt. Furthermore, attention to various facial regions was differentially modulated depending on social context. Using the Allen Institute's transcriptional atlas, we further established the colocalization of μ-opioid and κ-opioid receptor genes and OT genes at the OT-releasing sites in the human brain. These data across monkeys and humans support a regulatory relationship between the OT and opioid systems and suggest that administering OT under opioid antagonism may boost the therapeutic efficacy of OT for enhancing social cognition.T he efficacy of oxytocin (OT) in improving social abilities is under debate, largely due to frequently observed weak effect sizes and problems with replicability (1-3). Clinical trials of OT in autistic patients are ongoing, yet several studies have produced inconclusive results (4-8), demanding improvements to the efficacy and reliability of OT-based therapeutics. One strategy is to take advantage of existing physiological pathways in the brain that regulate OT activity to combinatorially enhance the oxytocinergic effects on social functions. In this regard, a promising candidate is the opioid system.In addition to the evolutionarily conserved OT system (9), the opioid system has been implicated in regulating social behavior. Excessive opioid activity in the brain has been discussed with respect to the development of early childhood autism (10). Abnormalities in central opioid levels have been observed in some individuals with autism, and clinical trials with predominantly μ-opioid blockers, such as naltrexone or naloxone (NAL), have yielded promising results in ameliorating both social and nonsocial deficits (11). Specifically, μ-opioid receptors have been studied in relation to reward, emotion, and behavior in the social domain (12) and are strongly expressed in reward-related regions of the primate brain (13). In rhesus macaques, carrying the G allele of the μ-opioid receptor gene OPRM1, compared with homozygous C alleles, is associated with stronger maternal attachment in infants (14) and more effective prevention of infant separation in mothers (15). Additionally, opioid agonists, such as morphine, decrease physical contact between social partners, whereas NAL administration increases solicitation for social contact, such as grooming and proximity (16)(17)(18)(19).The physiological relationship between the opi...

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Section: Resultssupporting

confidence: 66%

Oxytocin under opioid antagonism leads to supralinear enhancement of social attention

Monte

Piva

Anderson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Future experiments using this and other tasks in the rhesus monkey model have the potential to advance our understanding of the neural mechanisms of social behaviors that are disrupted in psychopathologies such as autism spectrum disorder and schizophrenia (Chang and Platt, 2013). …”

Section: Discussionmentioning

confidence: 99%

Social relevance drives viewing behavior independent of low-level salience in rhesus macaques

Solyst

Buffalo

2014

Front. Neurosci.

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Quantifying attention to social stimuli during the viewing of complex social scenes with eye tracking has proven to be a sensitive method in the diagnosis of autism spectrum disorders years before average clinical diagnosis. Rhesus macaques provide an ideal model for understanding the mechanisms underlying social viewing behavior, but to date no comparable behavioral task has been developed for use in monkeys. Using a novel scene-viewing task, we monitored the gaze of three rhesus macaques while they freely viewed well-controlled composed social scenes and analyzed the time spent viewing objects and monkeys. In each of six behavioral sessions, monkeys viewed a set of 90 images (540 unique scenes) with each image presented twice. In two-thirds of the repeated scenes, either a monkey or an object was replaced with a novel item (manipulated scenes). When viewing a repeated scene, monkeys made longer fixations and shorter saccades, shifting from a rapid orienting to global scene contents to a more local analysis of fewer items. In addition to this repetition effect, in manipulated scenes, monkeys demonstrated robust memory by spending more time viewing the replaced items. By analyzing attention to specific scene content, we found that monkeys strongly preferred to view conspecifics and that this was not related to their salience in terms of low-level image features. A model-free analysis of viewing statistics found that monkeys that were viewed earlier and longer had direct gaze and redder sex skin around their face and rump, two important visual social cues. These data provide a quantification of viewing strategy, memory and social preferences in rhesus macaques viewing complex social scenes, and they provide an important baseline with which to compare to the effects of therapeutics aimed at enhancing social cognition.

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“…imitation recognition | neonatal imitation | individual differences O xytocin is a neuropeptide that has wide-ranging effects on social behaviors and social perception, including increased emotion recognition and prosocial behavior (1,2). Animal studies present convergent evidence of oxytocin's positive effects on social behavior (2-6), including humans (1,7).…”

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confidence: 99%

Inhaled oxytocin increases positive social behaviors in newborn macaques

Simpson

Sclafani

Paukner

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Early caregiver-infant interactions are critical for infants' socioemotional and cognitive development. Several hormones and neuromodulators, including oxytocin, affect these interactions. Exogenous oxytocin promotes social behaviors in several species, including human and nonhuman primates. Although exogenous oxytocin increases social function in adults-including expression recognition and affiliation-it is unknown whether oxytocin can increase social interactions in infants. We hypothesized that nebulized oxytocin would increase affiliative social behaviors and such effects would be modulated by infants' social skills, measured earlier in development. We also hypothesized that oxytocin's effects on social behaviors may be due to its anxiolytic effects. We tested these hypotheses in a blind study by nebulizing 7-to 14-d-old macaques (n = 28) with oxytocin or saline. Following oxytocin administration, infants' facial gesturing at a human caregiver increased, and infants' salivary oxytocin was positively correlated with the time spent in close proximity to a caregiver. Infants' imitative skill (measured earlier in development: 1-7 d of age) predicted oxytocin-associated increases in affiliative behaviors-lip smacking, visual attention to a caregiver, and time in close proximity to a caregiver-suggesting that infants with higher propensities for positive social interactions are more sensitive to exogenous oxytocin. Oxytocin also decreased salivary cortisol, but not stressrelated behaviors (e.g., scratching), suggesting the possibility of some anxiolytic effects. To our knowledge, this study provides the first evidence that oxytocin increases positive social behaviors in newborns. This information is of critical importance for potential interventions aimed at ameliorating inadequate social behaviors in infants with higher likelihood of developing neurodevelopmental disorder.imitation recognition | neonatal imitation | individual differences

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Oxytocin and social cognition in rhesus macaques: Implications for understanding and treating human psychopathology

Cited by 61 publications

References 114 publications

Oxytocin under opioid antagonism leads to supralinear enhancement of social attention

Oxytocin under opioid antagonism leads to supralinear enhancement of social attention

Social relevance drives viewing behavior independent of low-level salience in rhesus macaques

Inhaled oxytocin increases positive social behaviors in newborn macaques

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