Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques ( Macaca mulatta )

In the citing paper

“Of the above-mentioned studies, four (20,22,24,25) achieved oxytocin concentrations in excess of 20pg/ml from basal levels of <5pg/ml, while Dal Monte et al. reported a rise to 80pg/ml after nasal spray, but no significant rise with a nebulariser (23).Modi et al. reported a 100-fold increase in plasma in the macaque (to >300pg/ml), and a rise to ~60pg/ml (from 10pg/ml) after nebulariser”

In the citing paper

“Chang et al. gave 25IU oxytocin to two macaques, and reported a rise in CSF from ~20 to ~50pg/ml at 35min (24).”

In the citing paper

“The intranasal dose administered in the present study has been associated with changes in central function in humans 58, and similar or smaller doses of oxytocin or vasopressin (24–48 IU for oxytocin; 40–80 IU for vasopressin) have been associated with elevations in peptide levels in the cerebrospinnal fluid in humans or macaques of no more than approximately 55 pg/ml in actual levels 70, 71, 72,”

In the citing paper

“neuropeptides have been shown to gain access to the brain following intranasal administration (Born et al., 2002;Chang et al., 2012).”

In the citing paper

“Ultimately, prosocial responses occur through multiple processes both within and across species, some of which may be modified by OXT (Brosnan, Talbot, et al., 2015; Chang et al., 2012; Mustoe et al., 2015) while others may not (this study).”

In the citing paper

“This work provides anatomical support for other findings in macaques, which indicate that IN-OXT treatment increases gaze following67, increases socially oriented gaze68, and alters social attention in a wide variety of contexts69–74.”

In the citing paper

“OT also enhances socially reinforced learning (Parr, 2014), and increases reward allocation to a partner monkey (Chang et al., 2012).”

In the citing paper

“This way the expected period of rise in OT levels (20–45 min) coincided with the post-treatment viewing period (Chang et al., 2012; Dal Monte et al., 2014b).”

In the citing paper

“Behavioral testing began 30 min after each treatment, given that animal studies in both rodents (53) and nonhuman primate (54, 55) have shown central elevations of OT concentration after 30 min from intranasal administration.”

In the citing paper

“This dose, administered intranasally, has been shown in nonhuman primates to increase OT levels in cerebrospinal fluid significantly (54) and to modulate social behavior (65), as well as to affect brain activity (66) and phasic activity of the parasympathetic nervous system (67) in humans.”

In the citing paper

“In rhesus macaques, three studies have found that treatment with IN-OT impacts social visual attention and looking behaviours in a variety of tasks (77-79).”

In the citing paper

“In rhesus macaques, for example, Chang et al. (2012) found that subjects that engaged in a food sharing task showed first greater selfish choices and after 2 h greater prosocial choices after inhaling oxytocin.”

In the citing paper

“Finally, in some studies oxytocin only increases positive perceptions or social motivations toward others (Chang et al., 2012; Shamay-Tsoory et al., 2013) and in other studies it also amplifies pre-existing social motivations or perceptions, whether positive or negative (De Dreu, 2012).”

In the citing paper

“More recently, Neumann et al. (2013) in mice and rats, and Chang et al. (2012) in rhesus monkeys showed that inhaled oxytocin arrives in the behaviorally-relevant parts of the brain and in the CSF, respectively, although the exact route remains elusive.”

In the citing paper

“That oxytocin release may depend more on an individuals' social perception of an interaction than on the properties of the interaction itself mirrors other studies on human and non-human primates which suggest that inhaled oxytocin changes individuals' perception or motivation toward a social context (Chang et al., 2012; Parr et al., 2013, for reviews see: Bartz et al., 2011; Olff et al., 2013).”

In the citing paper

“Studies using exogenous oxytocin have highlighted how a possible effect of oxytocin is to change individuals' social motivations or perceptions of a current social context, such that individuals that inhale oxytocin compared with those that do not, become more affiliative, attentive, prosocial or empathetic to the same social stimuli (e.g., Bartz et al., 2011; Chang et al., 2012; Parr et al., 2013”

In the citing paper

“Also, in monkeys, IN-OT or OT intake via a nebulizer (25 or 48 IU) increased OT CSF concentration compared to placebo (Chang et al. 2012; Dal Monte et al. 2014; Modi et al. 2014).”

In the citing paper

“In nonhuman primates, exogenous inhaled oxytocin promotes social donation behavior 26 and focal infusion of oxytocin into the amygdala significantly increases prosocial decisions 7 .”

In the citing paper

“There is accumulated research on the role of IN-OT in promoting social exploration, enhancing social motivation and attenuating social vigilance in nonhuman primate models (Chang et al. 2012; Chang and Platt 2014; Ebitz and Platt 2013; Parr et al. 2013; Putnam et al. 2016).”

In the citing paper

“It is estimated that only a small amount of intranasally administered oxytocin reaches the brain.33, 34, 46, 47”

In the citing paper

“Using a pediatric nebulizer, we recently showed that inhaled oronasal administration of OT increases its concentration in the cerebrospinal fluid (CSF), measured at 30 min post-delivery (Chang et al., 2012) (Fig. 1B).”

In the citing paper

“Oronasal nebulization of OT amplifies these self-regarding and other-regarding preferences in rhesus macaques (Chang et al., 2012).”

In the citing paper

“When choosing between allocating juice rewards to a recipient monkey and no one at all, exogenous OT enhances the baseline prosocial bias (Fig. 2A).”

In the citing paper

“Furthermore, inhaled OT significantly increases reaction times when the actor monkeys choose between donating juice rewards to the recipient monkey and no one (Chang et al., 2012) (Fig. 2C), inviting the possibility that OT promotes prosocial choices by increasing internal deliberative processing in rhesus macaques.”

In the citing paper

“By contrast, when choosing between delivering juice rewards to themselves and to the recipients, inhaled OT amplifies the self-regarding preference (i.e., delivering juice to only themselves over only the recipients), essentially eliminating the small number of prosocial choices in this competitive context (Fig. 2A).”

In the citing paper

“Amplified prosocial preference is accompanied by an increase in gaze shifts to the recipient monkeys’ face region following OT (Fig. 2B).”

In the citing paper

“Critically, the OT-treated actors do not increase such gaze shifts to the recipient monkeys when the juice rewards are delivered to the recipients by the experimenter (i.e., cued condition) (Chang et al., 2012).”

In the citing paper

“Based on these results, we conjecture that reduced vigilance might play a permissive role in social approach behavior, favoring increased attention to faces and eyes and subsequent enhancements in social cognition.”

In the citing paper

“The efficacy of the nebulized inhalation method for delivering OT to the CNS in alert rhesus macaques prior to experimental tasks (Chang et al., 2012; Modi et al., in press) makes it easier to compare neurophysiological results from animal studies with behavioral or neuroimaging results obtained from both healthy people and those with neuropsychiatric disorders.”

In the citing paper

“the exact transnasal-CNS route remains unknown, and the proportion of OXT that actually reaches the CNS is exceptionally small relative to the given dose (Born et al., 2002; Chang et al., 2012; Striepens et al., 2013; Dal Monte et al., 2014; Modi et al., 2014).”

In the citing paper

“These results suggest that intranasal administration rapidly upregulates OT levels in the brain and plasma during the timeframe of behavioral testing, and that OT clears the system several hours after testing.”