AUTHOR=Nerio-Morales Lina K. , Boender Arjen J. , Young Larry J. , Lamprea Marisol R. , Smith Adam S. 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 18 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1409316

DOI=10.3389/fnins.2024.1409316

ISSN=1662-453X

ABSTRACT=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.