Social touch-like tactile stimulation alleviates stress-induced anxiety-like behavior by enhancing the oxytocin level in the prefrontal cortex

Stress is a major contributor to the development and exacerbation of anxiety disorders. While social support is known to provide a buffering effect, the specific mechanisms remain poorly understood. This study investigated the neurobiological basis through which social touch alleviates stress-induced anxiety. Using a mouse model of chronic restraint stress, we demonstrated that a gentle, stroking tactile stimulus (mimicking social grooming) significantly reduced anxiety-like behaviors in the open field and elevated plus maze tests. Specifically, social touch reversed the stress-induced decrease in neuronal activity in the prelimbic cortex (PL) pyramidal neurons. Moreover, we found that the anxiolytic effect of social touch was mediated by a localized increase in oxytocin (OT) levels within the PL. Furthermore, administration of an OT receptor agonist into the PL mimicked the benefits of social touch, while an OT receptor antagonist blocked them. In conclusion, our findings reveal a direct pathway whereby affective social touch attenuates anxiety by enhancing oxytocin levels in the prefrontal cortex, thereby rescuing stress-impaired neuronal function. This provides a fundamental neurobiological explanation for the social buffering phenomenon and identifies the prefrontal cortex OT system as a potential therapeutic target for anxiety disorders. • Social touch, but not visual or olfactory social cues, reverses stress-induced anxiety-like behaviors in mice. • The anxiolytic effect of social touch-like tactile stimulation is mediated by the prelimbic cortex. • Social touch-like tactile stimulation restores the suppressed neuronal activity in the prelimbic cortex caused by chronic stress. • The behavioral and neural benefits require local oxytocin receptor activation in the prelimbic cortex.