Effects of intranasal oxytocin and vasopressin on cooperative behavior and associated brain activity in men

Summary

The neural mechanisms supporting social bonds between adult men remain uncertain. In this double-blind, placebo-controlled study, we investigate the impact of intranasally administered oxytocin (OT) and vasopressin (AVP) on behavior and brain activity among men in the context of an iterated Prisoner's Dilemma game, which models a real-life social situation. fMRI results show that, relative to both AVP and placebo, OT increases the caudate nucleus response to reciprocated cooperation, which may augment the reward of reciprocated cooperation and/or facilitate learning that another person can be trusted. OT also enhances left amygdala activation in response to reciprocated cooperation. Behaviorally, OT was associated with increased rates of cooperation following unreciprocated cooperation in the previous round compared with AVP. AVP strongly increased cooperation in response to a cooperative gesture by the partner compared with both placebo and OT. In response to reciprocated cooperation, AVP increased activation in a region spanning known vasopressin circuitry implicated in affiliative behaviors in other species. Finally, both OT and AVP increase amygdala functional connectivity with the anterior insula relative to placebo, which may increase the amygdala's ability to elicit visceral somatic markers that guide decision making. These findings extend our knowledge of the neural and behavioral effects of OT and AVP to the context of genuine social interactions.

Introduction

In nature, the paradigmatic social bond is that between mother and offspring. Research with animal models implicates both the oxytocin (OT) and dopamine (DA) systems in the establishment and maintenance of maternal attachment and caregiving. OT enables mothers to overcome avoidance of proximity to offspring and, together with dopamine, may render maternal caregiving rewarding (Swain et al., 2007, Insel, 2010). The OT and DA systems interact in the ventral striatum, implicating the latter in maternal motivation (Skuse and Gallagher, 2009, Strathearn et al., 2009). This mechanism also appears to mediate female attachment to adult male partners in pair-bonding voles (Liu and Wang, 2003, Young et al, 2005) and possibly humans (Bartels and Zeki, 2004, Aron et al., 2005, Fisher et al., 2005), prompting the suggestion that modification of neural systems involved in maternal care is a parsimonious mechanism for the evolution of adult female pair-bonding (Ross and Young, 2009).

Non-reproductive social bonds between unrelated adults have been less thoroughly investigated; however, similar mechanisms may be involved. Reciprocated cooperation from adult strangers activates the caudate nucleus (Rilling et al., 2002, Rilling et al., 2004, Delgado et al., 2005), a region known to receive DA projections from the midbrain, and caudate activation predicts future reciprocity (King-Casas et al., 2005). Intranasal OT is associated with increased trust (Kosfeld et al., 2005, Baumgartner et al., 2008, Andari et al., 2010), and a recent study presented evidence suggesting that OT mediates bonding among men in groups (De Dreu et al., 2010). Thus, OT and DA may interact to support bonds among adult men. Here, we administered OT to men as they played an iterated Prisoner's Dilemma (PD) game to determine if OT would augment activation in the caudate nucleus in response to reciprocated cooperation.

OT appears to reduce the salience of negative social stimuli and increase the salience of positive social stimuli (Heinrichs et al., 2003, Baumgartner et al., 2008, Guastella et al., 2008, Petrovic et al., 2008, Unkelbach et al., 2008, Heinrichs et al., 2009, Theodoridou et al., 2009, Gamer et al., 2010). Recent studies have revealed a potential neural mechanism for these effects. OT decreases the amygdala response to aversive social stimuli in men (Kirsch et al., 2005, Domes et al., 2007, Baumgartner et al., 2008, Petrovic et al., 2008, Gamer et al., 2010). Domes et al. (2007) also showed that OT decreased amygdala activation to all emotional face stimuli (including happy faces) in the right amygdala, and a recent study showed that OT increased amygdala activation to happy faces in the left amygdala (Gamer et al., 2010). Collectively, these studies led us to the prediction that OT would decrease the right amygdala response to unreciprocated cooperation (an aversive social stimulus), and perhaps also reciprocated cooperation, whereas OT would increase the left amygdala response to reciprocated cooperation.

While OT is anxiolytic, AVP is anxiogenic (Heinrichs et al., 2009) and may play a role in inter-male aggressive communication (Thompson et al., 2004, Thompson et al., 2006). Polymorphisms of the V1a vasopressin receptor (AVPR1a) have been linked with differences in amygdala responses to emotional facial expressions (Meyer-Lindenberg et al., 2009). Consequently, we predicted that AVP administration would be associated with increased amygdala activation and decreased rates of cooperation in our sample of male subjects.

Finally, we hypothesized that neuropeptide effects on behavior and brain activity would be specific to interactions with assumed human partners and would not be observed for interactions with known computer partners. Importantly, this is the first study to simultaneously test the effects of both OT and AVP on behavior and brain activation in a social interactive context.