G-1573

Protective Role of Oxytocin Against Early-Life Stress-Induced Working Memory Impairment: Evidence for Sex Differences

 Erfan Ehsani ¹ ℗, Mehrdad Jahanshahi ² ©, Leila Karimi-Zandi ³   

 
Abstract

Introduction: Early-life maternal separation is a well-established psychological stressor that can profoundly affect brain development and cognitive function later in life. Among the brain regions vulnerable to such early environmental challenges, the prefrontal cortex—critical for decision-making, attention, and working memory—is particularly sensitive. Previous studies have demonstrated that early-life stress can significantly impair working memory performance. Oxytocin, a neuropeptide recognized for its anti-stress and neuroprotective effects, has been shown to enhance cognitive processes, including memory and learning. Building on these insights, the present study aims to investigate the impact of oxytocin on working memory in a rat model of maternal separation. Methods and Materials: In this study, 30 Wistar rats (10 males and 20 females) were initially selected for mating and maintained under standard environmental conditions. Offspring resulting from these matings were enrolled in the experiment. To establish the maternal separation model, pups were separated from their mothers for 3 hours daily from postnatal day 2 (PND2) to day 21 (PND21). The treatment groups received daily oxytocin (1μg/μl) administration for 20 consecutive days. At the end of the study, working memory performance was assessed using the Y-maze test to evaluate the effects of maternal separation and the administered treatment. Results: Maternal separation caused significant working memory impairments in both male (p=0.004) and female (p=0.003) offspring. Treatment with oxytocin effectively reduced these cognitive deficits. Additionally, female offspring exhibited greater sensitivity to the effects of maternal separation stress compared to males (p=0.02). Conclusion and Discussion: This finding aligns with extensive evidence that early psychological stress disrupts prefrontal cortex development, a brain region critically involved in working memory, attention, and executive function. Early maternal separation impairs working memory in both male and female offspring, with females exhibiting greater vulnerability to these cognitive deficits. Intranasal oxytocin treatment provides a protective effect by effectively alleviating working memory impairments, likely through its neuroprotective and anti-stress properties. These findings underscore the critical role of early maternal care in cognitive development and highlight oxytocin as a promising therapeutic intervention for mitigating stress-induced working memory deficits.

Keywords: Maternal Separation, Working Memory, Oxytocin