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

Abstract

Converging evidence from humans and non-human animals indicates that the neurohypophysial hormone oxytocin (OT) evolved to serve a specialized function in social behavior in mammals. Although OT-based therapies are currently being evaluated as remedies for social deficits in neuropsychiatric disorders, precisely how OT regulates complex social processes remains largely unknown. Here we describe how a non-human primate model can be used to understand the mechanisms by which OT regulates social cognition and thereby inform its clinical application in humans. We focus primarily on recent advances in our understanding of OT-mediated social cognition in rhesus macaques (Macaca mulatta), supplemented by discussion of recent work in humans, other primates, and rodents. Together, these studies endorse the hypothesis that OT promotes social exploration both by amplifying social motivation and by attenuating social vigilance. This article is part of a Special Issue entitled Oxytocin and Social Behav.

Keywords: Amygdala; Inhalation; Intranasal; Nebulizer; Oxytocin; Rhesus macaques; Social cognition; Social decision-making; Social vigilance.

Figure 1

OT concentration in the cerebrospinal fluid (CSF) and social development in rhesus macaques. A. A nebulizer-based inhalation setup using a nebulizer (PARI Baby Nebulizer) in rhesus macaques. Notice that both nose and mouth are covered with the inhalation mask. Top, a training phase in which juice rewards are delivered through the nebulizer mask (about a week). Bottom, a treatment phase in which aerosolized OT or saline solutions are delivered to the monkeys. B. OT concentration in the CSF after inhaling 25 IU of OT (red) or saline (dark gray) in monkeys (5 minutes of nebulization at a 5 IU/min). The CSF samples were obtained from cervical punctures at 30 min post-delivery. Colored outlines on data points identify individual monkeys. Arrows with matching colors emphasize the CSF OT concentrations following saline (baseline) and OT inhalations within the same two monkeys. *, P < 0.05, Welch two-sample t test. C. Different levels of baseline CSF OT for mother-reared and nursery-reared male rhesus macaques across 18, 24, and 36 months of age. *, P <0.05, ANOVA. D. Enhanced duration of affiliative behavioral engagements (e.g., allogrooming and reciprocal male mounting) in mother-reared compared to nursery-reared monkeys. The inset shows reduced frequency of aggressive behaviors toward conspecifics for mother-reared compared to nursery-reared monkeys. *, P<0.05, ANOVA. [B adapted from: Chang, S.W.C., Barter, J.W., Ebitz, R.B., Watson, K.K., and Platt, M.L. (2012. Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta). Proc. Natl. Acad. Sci. 109, 959–964, Copyright (2012) National Academy of Sciences, U.S.A.; C, D adapted from: Winslow, J.T., Noble, P.L., Lyons, C.K., Sterk, S.M., and Insel, T.R. (2003). Rearing effects on cerebrospinal fluid oxytocin concentration and social buffering in rhesus monkeys. Neuropsychopharmacology 28, 910–918, Copyright (2003) Nature Publishing Group]

Figure 2

OT promotes social motivation in rhesus macaques. A. Choice preference index following inhaled OT (red) or saline (gray) administration for rewards delivered to: other (recipient monkey) versus (vs.) neither, self (actor) vs. other, and self vs. neither in the social reward-allocation task. Data points from self vs. other and self vs. neither are jittered on the left plot for visibility. The inset shows unjittered data from self vs. other trials. *, P < 0.05, Welch two-sample t test. B. Number of gaze shifts made to the recipient monkey after reward delivery over the course of each session on other vs. neither trials. *, P < 0.05, Welch two-sample t test. C. OT selectively increases the decision deliberation time in the other vs. neither context (choosing to deliver juice rewards to other or no one) in which actor rhesus monkeys show a preference for delivering juice rewards to another monkey. *, P < 0.05, Welch two-sample t test. [A – C adapted from: Chang, S.W.C., Barter, J.W., Ebitz, R.B., Watson, K.K., and Platt, M.L. (2012). Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta). Proc. Natl. Acad. Sci. 109, 959–964, Copyright (2012) National Academy of Sciences, U.S.A.]

Figure 3

OT regulates social vigilance in rhesus macaques. A. Inhaled OT selectively reduces monkeys’ species-typical choices to view dominant face images in a task in which monkeys choose to view the images of dominant high status monkeys, subordinate low status monkeys, female perinea, or gray square (Deaner et al., 2005). *, P < 0.05, Tukey LSD. B. Accompanied by the reduction in monkeys’ species-typical choices to view dominant face images (Fig. 3A), OT selectively eliminates typical reaction time facilitation of choosing to view dominant monkey faces. *, P < 0.05, post hoc LSD. C. Left, Examples of saccade residuals from trials with social distractors (upper) and nonsocial distractors (lower) presented at a neutral location relative to a target. Right, OT selectively reduces the typical saccade interferences (measured by the magnitude of deflections) to social distractors. *, P < 0.01, Bonferroni-corrected post doc Tukey LSD. D. Left, Attentional bias scores for facial expression stimuli categories after inhaled OT or placebo. Right, attentional bias scores for direct versus averted gaze trials after inhaled OT or placebo. OT reduces attention to emotional face stimuli (left), whereas it shows a trend of enhancing attention to facial stimuli with direct gaze (right). [A – C adapted from: Ebitz, R.B., Watson, K.K., and Platt, M.L. (2013). Oxytocin blunts social vigilance in the rhesus macaque. Proc. Natl. Acad. Sci. 110, 11630–11635, Copyright (2013) National Academy of Sciences, U.S.A.; D adapted from: Parr, L.A., Modi, M., Siebert, E., and Young, L.J. (2013). Intranasal oxytocin selectively attenuates rhesus monkeys’ attention to negative facial expressions. Psychoneuroendocrinology 38, 1748–1756, Copyright (2013) Elsevier]