Oxytocin (OT) is a mammalian hormone that is important for modulating social and emotional behavior. Studies in rodents have shown that OT is necessary for pair bonding, maternal behavior, and social recognition and in primates OT increases attention to social stimuli, reduces social vigilance, and enhances social reward. Because of these prosocial effects, OT has emerged as a leading potential pharmacotherapy for the treatment of social impairments associated with a wide variety of neurodevelopmental and psychiatric disorders, including social anxiety disorders, personality disorder, schizophrenia, and autism. Recent studies, for example, have shown that OT can be effective in improving the negative symptoms associated with these disorders. Despite these encouraging results, there are many procedural and biological questions remaining as to how and where OT acts to modulate social behavior, not only in social disorders but in typical behavior. Although the vast majority of studies in primates involve single-dose treatments, emerging data from rodents have revealed significant differences in behavior and oxytocin receptor density after chronic versus acute OT administration. Thus, it remains unknown how OT modulates social behavior in primates, its effect on brain and behavioral development, and the consequences of repeated administration in infancy when drug treatments are likely to have their greatest impact on reversing or suspending progression towards social impairment. Before powerful hormones should be given to young children, there needs to be a more thorough understanding of how OT affects normative behavioral and neural development in a relevant animal model. The present study will examine the effects of repeated administration of OT on the social behavior and neural development of rhesus monkeys. Monkeys will receive chronic OT administration over the first two years of life. During the 1st year, social attention will be measured using noninvasive eye-tracking, documenting the effects of OT on early emerging perceptual processes. In the 2nd and 3rd years, treatment-related differences in social behavior will be measured. Drug treatments will stop after year two, so behavioral assessments in year three will provide a measure of recovery. In year 4, subjects will receive two acute doses of OT to assess long-lasting changes in the sensitization of social behavior systems. Finally, the effects of OT on brain development will be measured longitudinally using resting state functional connectivity MRI that provides a quantification of the functional organization of brain networks. Together, these studies will provide seminal data on the long-term behavioral and neural effects of repeated OT administration early in primate development.

Public Health Relevance

Oxytocin (OT) is a neuromodulator important for the regulation of social and emotional behaviors in many species. Because of these effects, there is strong interest in using OT as a pharmacotherapy for the treatment of social impairments. In fact, several studies have now shown that OT can improve some of the negative behavioral symptoms in adult psychiatric populations. Despite these promising results, it remains unknown how OT regulates social behavior in primates, and what the behavioral and neural consequences may be if this powerful hormone were given repeatedly during early development. This project will examine the effects of repeated oxytocin administration on social behavior and neural development in infant monkeys as a first step towards understanding how this hormone modulates social behavior.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BBBP-Y (03))
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Simmons, Janine M
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Emory University
Other Domestic Higher Education
United States
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Simpson, Elizabeth A; Paukner, Annika; Pedersen, Eric J et al. (2018) Visual preferences for direct-gaze faces in infant macaques (Macaca mulatta) with limited face exposure. Dev Psychobiol :
Parr, Lisa A; Mitchell, Thomas; Hecht, Erin (2018) Intranasal oxytocin in rhesus monkeys alters brain networks that detect social salience and reward. Am J Primatol 80:e22915
Muschinski, Jana; Feczko, Eric; Brooks, Jenna M et al. (2016) The development of visual preferences for direct versus averted gaze faces in infant macaques (Macaca mulatta). Dev Psychobiol 58:926-936
Feczko, Eric J; Bliss-Moreau, Eliza; Walum, Hasse et al. (2016) The Macaque Social Responsiveness Scale (mSRS): A Rapid Screening Tool for Assessing Variability in the Social Responsiveness of Rhesus Monkeys (Macaca mulatta). PLoS One 11:e0145956