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Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans

D. A. Martins, N. Mazibuko, F. Zelaya, S. Vasilakopoulou, J. Loveridge, A. Oates, S. Maltezos, M. Mehta, S. Wastling, M. Howard, G. McAlonan, D. Murphy, S. C. R. Williams, A. Fotopoulou, U. Schuschnig, View ORCID ProfileY. Paloyelis
doi: https://doi.org/10.1101/563056
D. A. Martins
1Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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N. Mazibuko
1Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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F. Zelaya
1Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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S. Vasilakopoulou
1Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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J. Loveridge
1Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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A. Oates
2South London and Maudsley NHS Foundation Trust, London, UK
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S. Maltezos
3Adult Autism and ADHD Service, South London and Maudsley NHS Foundation Trust, London, UK & Institute of Psychiatry, Psychology and Neuroscience, King’s College London, UK
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M. Mehta
1Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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S. Wastling
1Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
4Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, UK
5Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK
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M. Howard
1Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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G. McAlonan
6Department of Forensic and Neurodevelopmental Science (SM), Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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D. Murphy
6Department of Forensic and Neurodevelopmental Science (SM), Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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S. C. R. Williams
1Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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A. Fotopoulou
7Department of Clinical, Educational and Health Psychology, University College London, London, UK
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U. Schuschnig
8PARI GmbH, Gräfelfing, Germany
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Y. Paloyelis
1Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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  • ORCID record for Y. Paloyelis
  • For correspondence: yannis.paloyelis@kcl.ac.uk
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ABSTRACT

Could nose-to-brain pathways mediate the effects of peptides such as oxytocin (OT) on brain physiology when delivered intranasally? We address this question by contrasting two methods of intranasal administration (a standard nasal spray, and a nebulizer expected to improve OT deposition in nasal areas putatively involved in direct nose-to-brain transport) to intravenous administration in terms of effects on regional cerebral blood flow during two hours post-dosing. We demonstrate that OT-induced decreases in amygdala perfusion, a key hub of the OT central circuitry, are explained entirely by OT increases in systemic circulation following both intranasal and intravenous OT administration. Yet we also provide robust evidence confirming the validity of the intranasal route to target specific brain regions. Our work has important translational implications and demonstrates the need to carefully consider the method of administration in our efforts to engage specific central oxytocinergic targets for the treatment of neuropsychiatric disorders.

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  • Updated version during peer-review

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Posted January 29, 2020.
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Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans
D. A. Martins, N. Mazibuko, F. Zelaya, S. Vasilakopoulou, J. Loveridge, A. Oates, S. Maltezos, M. Mehta, S. Wastling, M. Howard, G. McAlonan, D. Murphy, S. C. R. Williams, A. Fotopoulou, U. Schuschnig, Y. Paloyelis
bioRxiv 563056; doi: https://doi.org/10.1101/563056
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Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans
D. A. Martins, N. Mazibuko, F. Zelaya, S. Vasilakopoulou, J. Loveridge, A. Oates, S. Maltezos, M. Mehta, S. Wastling, M. Howard, G. McAlonan, D. Murphy, S. C. R. Williams, A. Fotopoulou, U. Schuschnig, Y. Paloyelis
bioRxiv 563056; doi: https://doi.org/10.1101/563056

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