Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques

Sara M. Freeman, Sridhar Samineni, Philip C. Allen, Diane Stockinger, Karen L. Bales, Granger G C Hwa, Jeffrey A Roberts

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1 IU/kg; 1 IU/kg; 5 IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5 min post-dose and gradually returned to baseline by 120 min. In contrast, a change in CSF OT was only observed at the highest IV dose (5 IU/kg) at 15 min post-dose and gradually returned to baseline by 120 min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15-30 min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently.

Original languageEnglish (US)
Pages (from-to)185-194
Number of pages10
JournalPsychoneuroendocrinology
Volume66
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

Fingerprint

Macaca
Oxytocin
Cerebrospinal Fluid
Intranasal Administration
Central Nervous System
Social Behavior
Neuropeptides
Macaca mulatta
Intravenous Administration
Cross-Over Studies
Primates
Haplorhini
Publications
Schizophrenia
Catheters
Pharmacokinetics
Body Weight

Keywords

  • Cerebrospinal fluid
  • ELISA
  • Nasal spray
  • Neuropeptide
  • Rhesus macaque

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Endocrine and Autonomic Systems

Cite this

Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques. / Freeman, Sara M.; Samineni, Sridhar; Allen, Philip C.; Stockinger, Diane; Bales, Karen L.; Hwa, Granger G C; Roberts, Jeffrey A.

In: Psychoneuroendocrinology, Vol. 66, 01.04.2016, p. 185-194.

Research output: Contribution to journalArticle

Freeman, Sara M. ; Samineni, Sridhar ; Allen, Philip C. ; Stockinger, Diane ; Bales, Karen L. ; Hwa, Granger G C ; Roberts, Jeffrey A. / Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques. In: Psychoneuroendocrinology. 2016 ; Vol. 66. pp. 185-194.
@article{e6ebbe0bcee3478494610a154330a6de,
title = "Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques",
abstract = "Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1 IU/kg; 1 IU/kg; 5 IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5 min post-dose and gradually returned to baseline by 120 min. In contrast, a change in CSF OT was only observed at the highest IV dose (5 IU/kg) at 15 min post-dose and gradually returned to baseline by 120 min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15-30 min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently.",
keywords = "Cerebrospinal fluid, ELISA, Nasal spray, Neuropeptide, Rhesus macaque",
author = "Freeman, {Sara M.} and Sridhar Samineni and Allen, {Philip C.} and Diane Stockinger and Bales, {Karen L.} and Hwa, {Granger G C} and Roberts, {Jeffrey A}",
year = "2016",
month = "4",
day = "1",
doi = "10.1016/j.psyneuen.2016.01.014",
language = "English (US)",
volume = "66",
pages = "185--194",
journal = "Psychoneuroendocrinology",
issn = "0306-4530",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques

AU - Freeman, Sara M.

AU - Samineni, Sridhar

AU - Allen, Philip C.

AU - Stockinger, Diane

AU - Bales, Karen L.

AU - Hwa, Granger G C

AU - Roberts, Jeffrey A

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1 IU/kg; 1 IU/kg; 5 IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5 min post-dose and gradually returned to baseline by 120 min. In contrast, a change in CSF OT was only observed at the highest IV dose (5 IU/kg) at 15 min post-dose and gradually returned to baseline by 120 min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15-30 min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently.

AB - Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1 IU/kg; 1 IU/kg; 5 IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5 min post-dose and gradually returned to baseline by 120 min. In contrast, a change in CSF OT was only observed at the highest IV dose (5 IU/kg) at 15 min post-dose and gradually returned to baseline by 120 min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15-30 min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently.

KW - Cerebrospinal fluid

KW - ELISA

KW - Nasal spray

KW - Neuropeptide

KW - Rhesus macaque

UR - http://www.scopus.com/inward/record.url?scp=84960859295&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960859295&partnerID=8YFLogxK

U2 - 10.1016/j.psyneuen.2016.01.014

DO - 10.1016/j.psyneuen.2016.01.014

M3 - Article

VL - 66

SP - 185

EP - 194

JO - Psychoneuroendocrinology

JF - Psychoneuroendocrinology

SN - 0306-4530

ER -