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.

Nonapeptide Receptor Distributions in Promising Avian Models for the Neuroecology of Flocking

“…Nonapeptide receptor autoradiography assays were carried out as previously described ( Perkeybile et al, 2015 ; Guoynes et al, 2018 ; Hartman et al, 2018 ). Sections were allowed to thaw in slide boxes for 1 h at room temperature and then placed in racks to dry.…”

Sex-dependent regulation of social reward by oxytocin: an inverted U hypothesis

“…Sex differences in the distribution and number of receptors for OT have been observed within specific brain regions, although these sex differences, like those for the expression levels of OT and AVP, are not entirely consistent across species [48,49]. The distribution of OTR binding tends to be greater in males compared to females in forebrain regions, such as the nucleus accumbens (NAc), where sex differences have been reported in a number of rodent species including rats, mice, and prairie vole [48,49,[71][72][73]. However, these male/female differences are not always consistent.…”

A Review of Oxytocin and Arginine-Vasopressin Receptors and Their Modulation of Autism Spectrum Disorder

“…To date, this technique has allowed researchers to manipulate genetic information (Halladay et al, 2009 ), allowing control over genetic factors that contribute to the development of neurodevelopmental disorders, potentially giving rise to new medical treatments (Avraham et al, 2017 ). Rodent models have been adopted in ASD studies to investigate mechanisms for prevention (Vuillermot et al, 2017 ), and potential therapeutic treatments (Chadman, 2017 ; Guoynes et al, 2017 ), as well as to better understand the involvement of the gut-brain axis (for a review see Nithianantharajah et al, 2017 ) and the immune system (Schwartzer et al, 2017 ) in ASD etiology. To illustrate this, we draw specific attention to the pivotal role that animal models have played in elucidating how maternal immune activation, a well-ascertained environmental risk factor, contributes to ASD.…”