Oxytocin (OT) functions as a neuromodulator in the central nervous system (CNS) to promote social behavior and affiliation in animals and. Because of its prosocial effects, researchers have begun to explore whether OT could be used as a novel pharmacotherapy to treat a variety of neuropsychiatric disorders characterized by social impairments, such as autism. Indeed, several studies have now emerged suggesting that intranasally administered (IN) OT can improve prosocial behavior in adults with high-functioning autism, including cooperation, reading facial expressions, and directing attention to the eye region in faces . However, the exact mechanisms by which IN-OT influence prosocial behavior in primates remain unclear, including whether OT acts centrally in the brain through the oxytocin receptor system (OXTR) or through peripheral feedback. Therefore, while OT is an extremely attractive potentials pharmacotherapy that could function to ameliorate social impairments and enhance prosocial behavior in humans, many questions remain about its mechanism of action and overall function. This is particularly true in nonhuman primates. Although they represent an ideal preclinical model for screening the behavioral and neurobiological effects of OT, only a handful of studies investigated the effect of OT on nonhuman primate social cognition. It is the goal of this study to compare the effect of IN-OT and intracerebroventricular (ICV) OT, and an OXTR-antagonist on tasks that address social perception social reward in rhesus monkeys. The tasks used are designed to mirror those used in studies of IN-OT in humans, and address some ofthe same social skills known to be impaired in autism, e.g., salience of social stimuli, social reward, recognition of familiar faces, and emotion categorization. Additionally, monkeys will be shown complex videos of familiar and unfamiliar monkeys engaged in social interactions during eye-tracking to determine how IN-OT affects the convergence of social attention. This project will provide seminal data on how OT affects social perception and social reward and contribute to it pharmacotherapeutic development.

Public Health Relevance

Oxytocin is a hormone that enhances prosocial behavior in humans and thus might be useful as a pharmacotherapy for improving the social impairments that characterize many neuropathological conditions, such as autism. However, preclinical models are needed to understand how oxytocin improves prosocial behavior and to ensure its safety and effective use. This project will examine how oxytocin affects social perception and social reward in rhesus monkeys as a first step in the development of drug treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
1P50MH100023-01
Application #
8657299
Study Section
Special Emphasis Panel (ZMH1-ERB-L (02))
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$304,019
Indirect Cost
$120,507
Name
Emory University
Department
Type
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Modi, Meera E; Connor-Stroud, Fawn; Landgraf, Rainer et al. (2014) Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques. Psychoneuroendocrinology 45:49-57
Freeman, Sara M; Inoue, Kiyoshi; Smith, Aaron L et al. (2014) The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta). Psychoneuroendocrinology 45:128-41
Mosher, Clayton P; Zimmerman, Prisca E; Gothard, Katalin M (2014) Neurons in the monkey amygdala detect eye contact during naturalistic social interactions. Curr Biol 24:2459-64
Freeman, S M; Walum, H; Inoue, K et al. (2014) Neuroanatomical distribution of oxytocin and vasopressin 1a receptors in the socially monogamous coppery titi monkey (Callicebus cupreus). Neuroscience 273:12-23
Rilling, James K; Young, Larry J (2014) The biology of mammalian parenting and its effect on offspring social development. Science 345:771-6
Skuse, David H; Lori, Adriana; Cubells, Joseph F et al. (2014) Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills. Proc Natl Acad Sci U S A 111:1987-92
K├Ânig, Seth D; Buffalo, Elizabeth A (2014) A nonparametric method for detecting fixations and saccades using cluster analysis: removing the need for arbitrary thresholds. J Neurosci Methods 227:121-31