Oxytocin (OT) is a potential treatment for multiple neuropsychiatric disorders. Since OT is a peptide, delivery by the intranasal (IN) route is the preferred method in clinical studies. Although studies have shown increased cerebrospinal fluid (CSF) OT levels following IN administration, this does not clearly demonstrate that the peripherally administered OT is entering the CSF. For example, it has been suggested that peripheral delivery of OT could lead to central release of endogenous OT. It is also unknown whether the IN route provides for more efficient entry of the peptide into the CSF compared to the IV route which requires blood brain barrier (BBB) penetration. To address these questions, we developed a sensitive and specific quantitative mass spectrometry assay that distinguishes labelled (d5-deuterated) from endogenous (d0) OT. We administered d5-oxytocin (80 IU) to 6 nonhuman primates via IN and IV routes as well as IN saline as a control condition. We measured plasma and CSF concentrations of administered and endogenous OT before (t=0) and after (t=10, 20, 30, 45, 60 minutes) d5-oxytocin dosing. We demonstrate CSF penetrance of d5, exogenous OT delivered by IN and IV administration. Peripheral administration of d5-OT did not lead to increased d0, endogenous OT in the CSF. This suggests that peripheral administration of OT does not lead to central release of endogenous OT. We also did not find that IN administration offered an advantage compared to IV administration with respect to achieving greater CSF concentrations of OT.

In Figure 1e and f, "F4 control" should be "Cre/tdTomato" and "F4Cre KO" should be "F4Cre/tdTomato". In addition, in the Figure1f legend, the first sentence should end with "(Cre/tdTomato: n = 10, F4Cre/tdTomato: n = 14)".In the 'Materials and Methods' section, under 'Electrophysiology,' the n values for evoked action potential recordings were omitted. The sentence 'For high-frequency stimulus-induced action potentials, the stimulus electrode was placed in the rostral part of VTA and a train of 100 Hz stimuli (1 s) was applied' should end with '(Cre/tdTomato: n=10, F4Cre/tdTomato: n=14).'Later in the same paragraph, in 'For recording evoked EPSCs (Cre/tdTomato, n=13, F4Cre/tdTomato, n=15; AMPA EPSCs were recorded at -70  mV and NMDA EPSCs were recorded at +40 mV)', the phrase 'Cre/tdTomato, n=13, F4Cre/tdTomato, n=15' should be deleted; those n values should have appeared at the end of the later sentence beginning 'Miniature ESPCs...'. The complete, corrected sentence is 'Miniature EPSCs (mEPSCs) were acquired in the presence of 0.5-1 μM TTX and 100 μM picrotoxin and semiautomatically detected by offline analysis using in-house software in Igor Pro (Wavemetrics, Portland, OR, USA) (Cre/tdTomato, n=13, F4Cre/tdTomato, n=15).'Finally, in the 'Materials and Methods' section, third sentence under 'Immunohistochemistry,' information for one TH antibody was omitted. The list of antibodies should end with 'or Millipore MAB5280, 1:1000-1:2000.'