Effects of chronic oxytocin on attention to dynamic facial expressions in infant macaques

Abstract

Studies in a variety of species have reported enhanced prosocial effects after an acute administration of the neuromodulating hormone, oxytocin (OT). Although the exact mechanisms underlying these effects are not fully understood, there is broad interest in developing OT into a treatment for social deficits. Only a few studies, however, have examined the effects of OT if given repeatedly during early development, the period when early intervention is likely to have the greatest benefits for reversing the progression towards social impairment. Those studies, exclusively in rodents, report mixed results. Some have shown enhancement of prosocial behavior, including increased social exploration, but others have shown anti-social effects, including increased aggression. In the present study, infant rhesus macaques were treated with a high-frequency (3× per week) or low-frequency (1× per week) dose of intranasal oxytocin (IN-OT) or placebo (IN-saline) between two and six months of age, after which their reactions to dynamic facial expressions (neutral, lipsmacking and threats) were measured. Results showed that IN-OT, compared to placebo, increased the time monkeys spent viewing the expression videos, but selectively reduced attention to the eyes in neutral faces in a dose dependent manner. The mechanism for this non-prosocial effect may be that repeated IN-OT administration down-regulates the expression of OT receptors in brain regions important for regulating social attention. Consequently, our results raise questions about the efficacy of implementing chronic IN-OT as a pharmacotherapy for the treatment of social deficits, particularly if given early in development. More work is needed, not only to identify optimal treatment schedules, but also to understand how IN-OT exerts its influences on the brain and behavior.

Keywords: Development; Eye-tracking; Facial expression; Gaze; Infant macaque; Oxytocin.

Figure 1

Methods used for administering IN-OT to monkeys under 16 weeks of age (left image) and over 16 weeks of age using a custom designed dosing box. The middle image shows the older infant inside the dosing box, while the image on the right shows the rear of the dosing box where the nebulizers are connected.

Figure 2

Custom designed eye-tracking chamber. Figure 2a shows the chair where the anesthetized mother was positioned. Figure 2b shows an overview of the exterior of the testing chamber and controls. Figure 2c shows the infant lying quietly on their mom and the stimulus presentation monitor. Figure 2d shows the infant lying quietly on the mom while watching the stimulus presentation monitor.

Figure 3

Mean total looking duration (+SEM) by monkeys in each treatment condition for each of the facial expression video categories. *p< 0.01; **p< 0.001

Figure 4

The mean log-transformed (+SEM) proportion of total looking duration directed at the eyes LookZones by monkeys in each treatment condition for each of the facial expression video categories. **p< 0.001

Figure 5

The mean log-transformed (+SEM) proportion of total looking duration directed at either the direct or averted eyes LookZones for each of the facial expression video categories. ^p< 0.05

Figure 6

Mean fixation duration (+SEM) by monkeys in each treatment condition for each of the facial expression video categories. ^p< 0.05; **p< 0.001