A comparison of methods to measure central and peripheral oxytocin concentrations in human and non-human primates

Abstract

Oxytocin (OT) concentration in the blood is considered to be a marker of its action in the brain. However, two problems have emerged when measuring OT level in the blood. First, it is unclear whether different methods of assessment lead to similar OT values. Second, it is unclear if plasma OT concentrations is informative on what OT does in the brain. To clarify these issues, we collected cerebrospinal fluid (CSF) from the brain ventricle of 25 patients during surgery to compare with plasma OT after simultaneous blood withdrawal. Additionally, we collected 12 CSF and blood samples from non-human primates while awake or under anaesthesia. We used four methods to assay OT concentrations: Commercial EIA with/without extraction, laboratory developed EIA with filtration and RIA with extraction. Three of these methods showed a positive correlation between plasma and CSF OT, suggesting a link between plasma and central OT, at least under specific testing conditions. However, none of the methods correlated to each other. Our results show major disagreements among methods used here to measure peripheral and brain OT and therefore they call for more caution when plasma OT is taken as a marker of central OT.

Oxytocin-mediated social enrichment promotes longer telomeres and novelty seeking

“…Axonal release of OT in the brain and in the circulatory system seem to be coordinated as central OT and peripheral OT in animals can be released simultaneously ( Wotjak et al, 1998 ). In humans, a correlation was shown between plasma and brain OT indicating that peripheral OT represents a suitable proxy of central OT ( Lefevre et al, 2017 ). It is also important to consider that, as they share a common ontogenetic origin from ectoderm, both brain and skin tissues contain similar collagenous proteins, reticulin, vasculature, and connective tissues such as fibroblasts and adipocytes.…”

“…Peripheral levels of OT (OTp) are assumed to reflect central releases of OT (OTc) in rats ( Wotjak et al, 1998 ) and humans ( Lefevre et al, 2017 ) with some procedural exceptions. Blood samples (0.5–0.7 mL) were taken 1–2 d prior to behavioural assessments ( Faraji et al, 2014 ) to measure plasma concentration of OT using solid phase radioimmunoassay (RIA) ( Alburges et al, 2000 ).…”

Opportunities and challenges for intranasal oxytocin treatment studies in nonhuman primates

“…Moreover, direct manipulation of the OT system by focal infusion into the macaque brain alters social gaze, prosocial decisions (Chang et al, 2015) and behavioral synchrony (Jiang & Platt, 2018), and the release of serotonin in brain regions implicated in social processing (Lefevre, Richard, et al, 2017). OT receptors in the rhesus monkey brain are highly expressed in regions involved with visual processing, including the nucleus basalis of Meynert, the pedunculopontine tegmental nucleus, the superficial gray layer of the superior colliculus, the trapezoid body, and the ventromedial hypothalamus (Freeman, Inoue, Smith, Goodman, & Young, 2014).…”

“…A small number of nonhuman primate studies have evaluated pharmacokinetic outcomes associated with these different routes of administration, though methodological differences have contributed to inconsistent findings. While rodent studies have demonstrated increases in both brain and plasma OT levels 30–60 min following nasal administration (Neumann, Maloumby, Beiderbeck, Lukas, & Landgraf, 2013), the relationship between central and peripheral levels of OT remains unclear, possibly due to temporal differences in OT bioavailability (Lefevre, Mottolese, et al, 2017). Here, we briefly summarize nonhuman primate studies reporting cerebrospinal fluid (CSF) outcome measures, which provide a direct and relatively noninvasive assessment of central nervous system (CNS) penetration routinely available for nonhuman primates.…”

Ocytocine, douleur et émotions

“…Simplifiant encore l'équation, une étude récente tend à montrer l'extrême variabilité existant entre différentes méthodes de dosage de l'ocytocine, fragilisant l'intégralité des conclusions basées sur les dosages dans le LCR et plasmatiques [45]. La controverse quant au mode d'administration de l'ocytocine, et à sa mesure, reste donc à ce jour réelle.…”