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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Neuropharmacology
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1409316

Limbic oxytocin receptor expression alters molecular signaling and social avoidance behavior in female prairie voles (Microtus ochrogaster)

Provisionally accepted
Lina K. Nerio Lina K. Nerio 1Arjen J. Boender Arjen J. Boender 2Larry J. Young Larry J. Young 2Marisol R. Lamprea Marisol R. Lamprea 3Adam S. Smith Adam S. Smith 1,4*
  • 1 Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, Kansas, United States
  • 2 Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, United States
  • 3 Department of Psychology, School of Human Sciences, Universidad Nacional de Colombia, Bogotá, Colombia
  • 4 Program in Neuroscience, School of Pharmacy, University of Kansas, Lawrence, United States

The final, formatted version of the article will be published soon.

    Social anxiety disorder (SAD) is one of the most common and disabling anxiety disorders. This condition is highly prevalent in women and is characterized by generalized social avoidance, often comorbid with other psychiatric diseases. The social defeat paradigm is the most representative animal model to study SAD and its underlying neural mechanisms. We have previously reported that defeat progressively reduces oxytocin receptors (OXTR) in the nucleus accumbens (NAc), anterior cingulate cortex (ACC), and basolateral amygdala (BLA) over an eight-week period in females prairie voles (Microtus ochrogaster). However, the functional significance of OXTR in stress-induced social avoidance in females is poorly understood. Oxytocin receptors activate the mitogen-activated protein kinase (MAPK) pathway, which has been previously associated with the anxiolytic effects of oxytocin. Here, we found that social defeat reduced OXTR binding in the NAc and affected MAPK pathway activity and oxytocin availability. These results were region-specific and sensitive to exposure to a behavioral test involving social novelty. Additionally, we showed that OXTR knockdown in the NAc, ACC, and BLA induced social avoidance and decreased basal MAPK activity in the NAc. Finally, we found that OXTR knockdown was associated with less availability of oxytocin in the PVN. These results show that dysregulation of the oxytocin system and MAPK signaling pathway in the NAc, ACC, and BLA are important in social behavior disruptions in female voles. This dysregulation could therefore play an important role in the etiology of SAD in women.

    Keywords: Oxytocin receptor (OXTR), social defeat stress, Prairie vole (Microtus ochrogaster), Nucleus accumbens (NA), Anterior cingulate (ACC), Basolateral amygadaloid (BLA), female

    Received: 29 Mar 2024; Accepted: 01 Jul 2024.

    Copyright: © 2024 Nerio, Boender, Young, Lamprea and Smith. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Adam S. Smith, Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, Kansas, United States

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