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. 2020 Jun 3;11(1):2783.
doi: 10.1038/s41467-020-15942-1.

Labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques

M R Lee #  1 , T A Shnitko #  2 , S W Blue  2 , A V Kaucher  3 , A J Winchell  3 , D W Erikson  3 , K A Grant  2   4 , L Leggio  5   6   7   8
Affiliations

Labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques

M R Lee et al. Nat Commun. .

Abstract

Oxytocin may have promise as a treatment for neuropsychiatric disorders. Its therapeutic effect may depend on its ability to enter the brain and bind to the oxytocin receptor. To date, the brain tissue penetrance of intranasal oxytocin has not been demonstrated. In this nonhuman primate study, we administer deuterated oxytocin intranasally and intravenously to rhesus macaques and measure, with mass spectrometry, concentrations of labeled (exogenously administered) and endogenous oxytocin in 12 brain regions two hours after oxytocin administration. Labeled oxytocin is quantified after intranasal (not intravenous) administration in brain regions (orbitofrontal cortex, striatum, brainstem, and thalamus) that lie in the trajectories of the olfactory and trigeminal nerves. These results suggest that intranasal administration bypasses the blood-brain barrier, delivering oxytocin to specific brain regions, such as the striatum, where oxytocin acts to impact motivated behaviors. Further, high concentrations of endogenous oxytocin are in regions that overlap with projection fields of oxytocinergic neurons.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Cerebrospinal fluid (CSF) d5 oxytocin (OT) concentrations: time course of d5OT concentrations in monkey cerebrospinal fluid (CSF) after intravenous (IV) administration of 80 and 40 IU d5OT (N = 6).
No d5OT was detected after intranasal (IN) administration of 80 IU d5OT. Limit of quantification = 100 pg/ml.
Fig. 2
Fig. 2. Plasma d5 oxytocin (OT) concentrations: time course of d5OT concentrations in monkey plasma after intravenous (IV) and intranasal (IN) administration of 80 and 40 IU d5OT (N = 6).
Limit of quantification = 100 pg/ml.
Fig. 3
Fig. 3. Cerebrospinal fluid (CSF) endogenous (d0) oxytocin (OT) concentrations: time course of d0OT in monkey cerebrospinal fluid (CSF) at baseline (Time = 0) and after intranasal (IN) d5OT 80 and 40 IU; after intravenous (IV) d5OT 80 and 40 IU.
Limit of quantification = 10 pg/ml.
See this image and copyright information in PMC

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