Labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques
| Autor: | Steven W. Blue, A. V. Kaucher, A. J. Winchell, Mary R. Lee, Kathleen A. Grant, Tatiana A. Shnitko, David W. Erikson, Lorenzo Leggio |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine endocrine system Physiology Science Thalamus General Physics and Astronomy Endogeny Striatum Pharmacology Oxytocin Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Endocrinology 0302 clinical medicine Limit of Detection Animals Medicine lcsh:Science Administration Intranasal Multidisciplinary Dose-Response Relationship Drug Staining and Labeling Drug discovery business.industry Brain General Chemistry Macaca mulatta Oxytocin receptor 030104 developmental biology Female lcsh:Q Nasal administration Orbitofrontal cortex Brainstem business hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-10 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-15942-1 |
| Popis: | 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. The location and extent of intranasal oxytocin brain penetrance has not been shown. Here the authors show that oxytocin, administered intranasally, enters brain regions along the trajectories of the olfactory and trigeminal nerves and there, reaches biologically relevant concentrations. |
| Databáze: | OpenAIRE |
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