Chronic Intranasal Oxytocin has Dose-dependent Effects on Central Oxytocin and Vasopressin Systems in Prairie Voles (Microtus ochrogaster)

C. D. Guoynes, T. C. Simmons, G. M. Downing, S. Jacob, Marjorie Solomon Friedman, K. L. Bales

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Oxytocin (Oxt) is a neuropeptide with many functions, including modulation of social behavior(s) and anxiety. Due to its notable pro-social effects, it has been proposed as a treatment in the management of neuropsychiatric disorders, such as autism spectrum disorder (ASD), schizophrenia, and social anxiety; however, effects of long-term daily treatment are still being explored. Previously, we have shown that in male prairie voles (Microtus ochrogaster) exposure to Oxt during the peri-adolescent period impaired adult pair bonding in a dose-dependent fashion. In females, the medium dose used (0.8 IU/kg) appeared to facilitate pair bonding, and the low and medium doses were associated with fewer lines crossed in the open field. In this study, we examined central receptor binding and immunoreactive (IR) protein for Oxt and vasopressin (Avp), a closely related peptide. Voles were treated with saline vehicle, or one of three doses of Oxt (0.08, 0.8, 8.0 IU/kg) for three weeks from postnatal days 21 to 42, and euthanized as adults. We used autoradiography to examine Oxt and Avp receptor binding and immunohistochemistry to examine Oxt and Avp – IR cells in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Females that received the medium dose of Oxt had higher Oxt receptor binding in the nucleus accumbens shell (NAS), while males that received the medium dose had lower Avp-IR cells in the PVN. In summary, we found sex-specific effects of long-term exposure to intranasal Oxt on the Oxt and Avp systems at the weight-adjusted dose currently being used in clinical trials in humans.

Original languageEnglish (US)
Pages (from-to)292-302
Number of pages11
JournalNeuroscience
Volume369
DOIs
StatePublished - Jan 15 2018

Fingerprint

Arvicolinae
Oxytocin
Vasopressins
Oxytocin Receptors
Anxiety
Vasopressin Receptors
Supraoptic Nucleus
Grassland
Social Behavior
Nucleus Accumbens
Neuropeptides
Autoradiography
Schizophrenia
Carrier Proteins
Immunohistochemistry
Clinical Trials
Weights and Measures
Peptides
Therapeutics

Keywords

  • autism
  • intranasal
  • oxytocin
  • vasopressin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chronic Intranasal Oxytocin has Dose-dependent Effects on Central Oxytocin and Vasopressin Systems in Prairie Voles (Microtus ochrogaster). / Guoynes, C. D.; Simmons, T. C.; Downing, G. M.; Jacob, S.; Friedman, Marjorie Solomon; Bales, K. L.

In: Neuroscience, Vol. 369, 15.01.2018, p. 292-302.

Research output: Contribution to journalArticle

@article{73c9062e4575480a8ec8aa800b2a4e12,
title = "Chronic Intranasal Oxytocin has Dose-dependent Effects on Central Oxytocin and Vasopressin Systems in Prairie Voles (Microtus ochrogaster)",
abstract = "Oxytocin (Oxt) is a neuropeptide with many functions, including modulation of social behavior(s) and anxiety. Due to its notable pro-social effects, it has been proposed as a treatment in the management of neuropsychiatric disorders, such as autism spectrum disorder (ASD), schizophrenia, and social anxiety; however, effects of long-term daily treatment are still being explored. Previously, we have shown that in male prairie voles (Microtus ochrogaster) exposure to Oxt during the peri-adolescent period impaired adult pair bonding in a dose-dependent fashion. In females, the medium dose used (0.8 IU/kg) appeared to facilitate pair bonding, and the low and medium doses were associated with fewer lines crossed in the open field. In this study, we examined central receptor binding and immunoreactive (IR) protein for Oxt and vasopressin (Avp), a closely related peptide. Voles were treated with saline vehicle, or one of three doses of Oxt (0.08, 0.8, 8.0 IU/kg) for three weeks from postnatal days 21 to 42, and euthanized as adults. We used autoradiography to examine Oxt and Avp receptor binding and immunohistochemistry to examine Oxt and Avp – IR cells in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Females that received the medium dose of Oxt had higher Oxt receptor binding in the nucleus accumbens shell (NAS), while males that received the medium dose had lower Avp-IR cells in the PVN. In summary, we found sex-specific effects of long-term exposure to intranasal Oxt on the Oxt and Avp systems at the weight-adjusted dose currently being used in clinical trials in humans.",
keywords = "autism, intranasal, oxytocin, vasopressin",
author = "Guoynes, {C. D.} and Simmons, {T. C.} and Downing, {G. M.} and S. Jacob and Friedman, {Marjorie Solomon} and Bales, {K. L.}",
year = "2018",
month = "1",
day = "15",
doi = "10.1016/j.neuroscience.2017.11.037",
language = "English (US)",
volume = "369",
pages = "292--302",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Chronic Intranasal Oxytocin has Dose-dependent Effects on Central Oxytocin and Vasopressin Systems in Prairie Voles (Microtus ochrogaster)

AU - Guoynes, C. D.

AU - Simmons, T. C.

AU - Downing, G. M.

AU - Jacob, S.

AU - Friedman, Marjorie Solomon

AU - Bales, K. L.

PY - 2018/1/15

Y1 - 2018/1/15

N2 - Oxytocin (Oxt) is a neuropeptide with many functions, including modulation of social behavior(s) and anxiety. Due to its notable pro-social effects, it has been proposed as a treatment in the management of neuropsychiatric disorders, such as autism spectrum disorder (ASD), schizophrenia, and social anxiety; however, effects of long-term daily treatment are still being explored. Previously, we have shown that in male prairie voles (Microtus ochrogaster) exposure to Oxt during the peri-adolescent period impaired adult pair bonding in a dose-dependent fashion. In females, the medium dose used (0.8 IU/kg) appeared to facilitate pair bonding, and the low and medium doses were associated with fewer lines crossed in the open field. In this study, we examined central receptor binding and immunoreactive (IR) protein for Oxt and vasopressin (Avp), a closely related peptide. Voles were treated with saline vehicle, or one of three doses of Oxt (0.08, 0.8, 8.0 IU/kg) for three weeks from postnatal days 21 to 42, and euthanized as adults. We used autoradiography to examine Oxt and Avp receptor binding and immunohistochemistry to examine Oxt and Avp – IR cells in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Females that received the medium dose of Oxt had higher Oxt receptor binding in the nucleus accumbens shell (NAS), while males that received the medium dose had lower Avp-IR cells in the PVN. In summary, we found sex-specific effects of long-term exposure to intranasal Oxt on the Oxt and Avp systems at the weight-adjusted dose currently being used in clinical trials in humans.

AB - Oxytocin (Oxt) is a neuropeptide with many functions, including modulation of social behavior(s) and anxiety. Due to its notable pro-social effects, it has been proposed as a treatment in the management of neuropsychiatric disorders, such as autism spectrum disorder (ASD), schizophrenia, and social anxiety; however, effects of long-term daily treatment are still being explored. Previously, we have shown that in male prairie voles (Microtus ochrogaster) exposure to Oxt during the peri-adolescent period impaired adult pair bonding in a dose-dependent fashion. In females, the medium dose used (0.8 IU/kg) appeared to facilitate pair bonding, and the low and medium doses were associated with fewer lines crossed in the open field. In this study, we examined central receptor binding and immunoreactive (IR) protein for Oxt and vasopressin (Avp), a closely related peptide. Voles were treated with saline vehicle, or one of three doses of Oxt (0.08, 0.8, 8.0 IU/kg) for three weeks from postnatal days 21 to 42, and euthanized as adults. We used autoradiography to examine Oxt and Avp receptor binding and immunohistochemistry to examine Oxt and Avp – IR cells in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Females that received the medium dose of Oxt had higher Oxt receptor binding in the nucleus accumbens shell (NAS), while males that received the medium dose had lower Avp-IR cells in the PVN. In summary, we found sex-specific effects of long-term exposure to intranasal Oxt on the Oxt and Avp systems at the weight-adjusted dose currently being used in clinical trials in humans.

KW - autism

KW - intranasal

KW - oxytocin

KW - vasopressin

UR - http://www.scopus.com/inward/record.url?scp=85037622621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037622621&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2017.11.037

DO - 10.1016/j.neuroscience.2017.11.037

M3 - Article

C2 - 29183825

AN - SCOPUS:85037622621

VL - 369

SP - 292

EP - 302

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

ER -