While this task is different in structure than the typical trust game, as implemented by Zak, Kurzban, and Matzner[25], the common features of monetary vulnerability and outcomes contingent on joint decision making result in a task that was expected to replicate the differences in endogenous oxytocin observed in that work

While this task is different in structure than the typical trust game, as implemented by Zak, Kurzban, and Matzner[25], the common features of monetary vulnerability and outcomes contingent on joint decision making result in a task that was expected to replicate the differences in endogenous oxytocin observed in that work. significant relationship between plasma oxytocin concentrations and trusting or trustworthy behavior. In light of these findings, previous published work that used oxytocin immunoassays without sample extraction should be reexamined and future research exploring links between endogenous human oxytocin and trust or social behavior should proceed RNASEH2B with careful consideration of methods and appropriate biofluids for analysis. == Introduction == Interest in the function and effects of the neuropeptide oxytocin in humans has expanded rapidly. Diverging greatly from oxytocins well known roles in parturition and lactation, widely-publicized results have implicated oxytocin in a range of complex social and psychological phenomena[1]. Oxytocin has been reported to induce anxiolytic effects[2], to reduce food intake and adiposity[3], to facilitate social interaction, bonding, and trust[4][6], to ameliorate social or emotional deficits associated with psychopathologies[7],[8], and to attenuate the effects of paederosidic acid methyl ester psychostimulants[9]. These results have significantly impacted their respective fields and have motivated ongoing research into oxytocin as a pharmacologic intervention to ameliorate causes or symptoms of various disorders[10]. The evidence supporting intervention studies and a significant role for oxytocin in psychological phenomena is generally derived from three primary sources: (1) assays of peripheral and/or central oxytocin in rodent models, (2) assays of endogenous peripheral oxytocin in humans, and (3) the results of exogenous oxytocin administration studies in humans, either via peripheral infusion or intranasal spray. The work described here focused on quantitative analysis of endogenous oxytocin in human blood plasma as a function of trusting or trustworthy behavior. While administration studies are not without concern and criticism[11], we have found that there has been limited verification of oxytocin assays leading to concerns that imprecise assays may have impacted the validity of results that have been reported in the literature to date[12]. The present study therefore focused on coupling assay verification paederosidic acid methyl ester with replication of the widely-reported paederosidic acid methyl ester link between oxytocin and trusting and trustworthy behavior. Oxytocin is a nonapeptide produced both in the central nervous system (CNS) and many tissues throughout the periphery. The psychological effects of oxytocin are likely associated with hypothalamic production and paederosidic acid methyl ester release, but the gastrointestinal tract, heart, uterus, testes, corpus luteum, and placenta also secrete oxytocin[13]. Receptors are found in a similar variety of tissues. As will be discussed further below, there is considerable disagreement regarding typical concentrations of oxytocin in human plasma. Nevertheless, it appears that normal human circulating concentrations are well below 1 ng/mL[14]. The low concentration of oxytocin in the periphery coupled with practical considerations of cost and throughput have favored detection using immunoassays with either radiolabeling or enzyme-linked optical absorptive reporters. Such immunoassays can be highly specific and sensitive; however, this specificity and sensitivity depends upon optimized procedures as well as components including the choice of antibody and biofluid isolated for assay. The chosen biofluid (e.g., blood plasma) may contain elements that cause interference and nonspecific binding for the analyte targeted by the assay[14]. One might assume that the psychoactive properties of oxytocin are solely dependent on activity in the CNS, and consequently researchers should focus on assaying oxytocin in cerebrospinal fluid (CSF). However, there is evidence for complex feedback both within the periphery and between the CNS and the periphery[3],[11]that can result in coordinated, though not coupled, release[15]. Oxytocin also does appear to cross the blood-brain barrier, though in very small quantities[16]; thus, it is possible that peripherally released oxytocin exerts some direct influence on the CNS. As a practical matter, research on oxytocin as a biomarker in humans has most frequently involved assays of plasma levels due to the invasive nature, procedural complexity, and safety concerns associated with sampling CSF. Research conducted with animal models has enabled the assessment of CSF oxytocin with findings that are generally consistent with the roles of oxytocin mentioned above. Some caution is warranted in extending results to human behavior, in particular from data using rodent models. Zhang et al.[17]used two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) to demonstrate that endogenous plasma oxytocin concentrations in rats are approximately 2000-fold higher than those observed in humans. Prairie voles, another common model for oxytocin research, have been reported to exhibit endogenous oxytocin concentrations well in excess of those of rats[18]. This large mean difference in circulating levels of oxytocin is not absolute evidence of variance in physiological mechanism or effects since, for example, aspects of receptor affinity and density could be lower.