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

D A Martins, Ndabezinhle Mazibuko, Fernando Zelaya, S Vasilakopoulou, J Loveridge, A Oates, S. Maltezos, Mitul Mehta, Stephen Wastling, M Howard, Grainne McAlonan, Declan Murphy, Steven Williams, A Fotopoulou, Uwe Schuschnig, Yannis Paloyelis

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85 Citations (Scopus)
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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.
Original languageEnglish
Article number1160
Number of pages16
JournalNature Communications
Volume11
Issue number1
Early online date3 Mar 2020
DOIs
Publication statusPublished - 3 Mar 2020

Keywords

  • oxytocin
  • intranasal
  • intravenous
  • nose-to-brain transport
  • arterial spinal labelling

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