期刊
MOLECULAR PSYCHIATRY
卷 23, 期 1, 页码 115-122出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2017.27
关键词
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资金
- Bench-to-Bedside (B2B) - National Institutes of Health (NIH) Office of Behavioral and Social Sciences Research (OBSSR), NIH intramural funding [ZIA-AA000218]
- Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Intramural Research Program (IRP) of the National Institute on Drug Abuse (NIDA)
- ZIA [MH002928-01]
- National Center for Advancing Translational Sciences (NCATS), NIH [1UH2TR000963]
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UH2TR000963] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [ZIAMH002928] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [ZIAAA000218] Funding Source: NIH RePORTER
Oxytocin (OT) is a potential treatment for multiple neuropsychiatric disorders. As 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 unequivocably 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 intravenous (IV) route, which requires blood-brain barrier penetration. To address these questions, we developed a sensitive and specific quantitative mass spectrometry assay that distinguishes labeled (d5-deuterated) from endogenous (d0) OT. We administered d5 OT (80 IU) to six 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 and 60 min) d5 OT 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.
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