Acute Restraint Stress Enhances Prosocial Behavior in Rats via Oxytocin and Fear-Related Circuits

Background: Stress is a critical determinant of social behavior, with oxytocin playing a key role in buffering stress effects and facilitating social bonding. However, the relationship between stress-induced fear and oxytocin-associated sociability remains unclear, particularly in contexts reminiscent of prior stress. This study investigates whether acute restraint stress (ARS) alters anxiety-related behaviors and prosocial choices, and whether these effects can be modulated by pharmacological intervention targeting the oxytocin and corticotropin-releasing hormone (CRH) systems. Methods: Sprague-Dawley rats were subjected to ARS and assessed for anxiety-like behavior using the elevated T-maze (ETM) and for prosocial behavior using the social choice test (SCT). The effects of the oxytocin receptor antagonist L-368899 and CRH receptor antagonist antalarmin were evaluated in this paradigm. Plasma corticosterone was checked peripherally and the tissue concentrations of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) were measured in the hippocampus, medial prefrontal cortex (mPFC), and amygdala to assess stress-related neurochemical changes in the fear circuit. Results: (i) ARS rats showed a significant increase in prosocial preference compared to control, an effect blocked by L-368899 or antalarmin. (ii) ARS rats exhibited reduced corticosterone levels, together with shorter avoidance latency, and longer escape latency in the ETM. (iii) Neurochemically, ARS rats had decreased DA and increased NE levels in the mPFC, both of which were normalized by L-368899 treatment. Conclusions: Oxytocin modulates stress-induced alterations in monoaminergic activity within the mPFC, influencing social choice behavior. These findings provide new insights into the neurobiological mechanisms underlying stress-related sociability and the context-dependent role of oxytocin in fear memory and social behavior.