Saliva oxytocin measures do not reflect peripheral plasma concentrations after intranasal oxytocin administration in men

Abstract

Oxytocin plays an important role in social behavior. Thus, there has been significant research interest for the role of the oxytocin system in several psychiatric disorders, and the potential of intranasal oxytocin administration to treat social dysfunction. Measurement of oxytocin concentrations in saliva are sometimes used to approximate peripheral levels of oxytocin; however, the validity of this approach is unclear. In this study, saliva and plasma oxytocin was assessed after two doses of Exhalation Delivery System delivered intranasal oxytocin (8 IU and 24 IU), intravenous oxytocin (1 IU) and placebo in a double-dummy, within-subjects design with men. We found that intranasal oxytocin (8 IU and 24 IU) administration increased saliva oxytocin concentrations in comparison to saliva oxytocin concentration levels after intravenous and placebo administration. Additionally, we found that saliva oxytocin concentrations were not significantly associated with plasma oxytocin concentrations after either intranasal or intravenous oxytocin administration. Altogether, we suggest that saliva oxytocin concentrations do not accurately index peripheral oxytocin after intranasal or intravenous oxytocin administration, at least in men. The data indicates that elevated oxytocin saliva levels after nasal delivery primarily reflect exogenous administered oxytocin that is cleared from the nasal cavity to the oropharynx, and is therefore a weak surrogate for peripheral blood measurements.

Salivary and plasmatic oxytocin are not reliable trait markers of the physiology of the oxytocin system in humans

“…The lack of increase in salivary oxytocin after the intravenous administration of exogenous oxytocin that was consistently found in our study and in a previous study ( Quintana et al, 2018 ) also raises the question of how oxytocin reaches the saliva if not from the blood. Currently, there is no evidence of direct acinar secretion or direct nerve terminals release of oxytocin to the saliva; therefore, transport from the blood remains as the most plausible mechanism of appearance of oxytocin in the saliva.…”

“…We could replicate previous evidence that intravenous oxytocin does not increase salivary oxytocin ( Quintana et al, 2018 ) and extended it by showing that the lack of increase in salivary oxytocin is not limited to the specific low dose of intravenous OT that was previously used (1IU) and that it is not driven by the insufficient sensitivity of the OT measurement method which had resulted in more than 50% of the saliva samples being discarded in the previous study ( Quintana et al, 2018 ). Therefore, our data supports the notion that increases in salivary oxytocin after its intranasal administration most likely reflect drip-down oxytocin from the nasal cavity ( Quintana et al, 2018 ). If this is the case then oxytocin elevations in saliva are mainly driven by non-absorbed exogenous oxytocin and therefore their use to estimate levels of systemic absorption or predict treatment effects after intranasal oxytocin administration is not valid.…”

“…In a previous study using enzyme-linked immunosorbent assay, the administration of low and medium doses of intranasal oxytocin (8 and 24 IU) elevated oxytocin concentrations in saliva, but the administration of a low dose (1 IU) intravenously had no effect. Moreover, concentrations of oxytocin in plasma and saliva did not correlate at baseline or after the administration of exogenous oxytocin for either route ( Quintana et al, 2018 ). These data suggest that salivary oxytocin is a weak surrogate measure for peripheral blood levels.…”

Ejaculate Collection Influences the Salivary Oxytocin Concentrations in Breeding Male Pigs

“…In humans, oxytocin reaches the salivary glands via blood circulation through active transport mechanisms [31]. However, the dynamic of oxytocin in both fluids (blood and saliva) could be different, since saliva concentrations of oxytocin do not reflect peripherally circulating oxytocin after exogenous administration in humans [32]. Martin et al [33] found that oxytocin concentrations in human saliva are more correlated with those in cerebrospinal fluid, and therefore with central oxytocin, than with those of blood plasma.…”

Is Oxytocin “Nature’s Medicine”?

“…Several studies have revealed reliable variations in oxytocin concentration, especially in rapid response to specific experiences, such as anticipation of breast feeding ( White-Traut et al, 2009 ), sexual stimulation, exercise, affiliative social contact, and psychologic stress ( Jong et al, 2015 ; MacLean et al, 2017a ). However, the relationships between concentrations of peptides in saliva, blood, and peptide concentrations in the source brain nuclei are not yet well-understood ( Quintana et al, 2018 ).…”