To investigate the regulatory role of oxytocin receptors (Oxtr) in the basal forebrain in chronic social defeat stress (CSDS) -induced social avoidance behavior.

c-Fos immunofluorescence staining, stereotaxic injection, fiber photometry calcium recording, and RNAscope in situ hybridization were employed to compare behavioral performance and neural activity between wild-type mice and those with basal forebrain-specific Oxtr deletion under the CSDS model.

Compared with the control group without CSDS exposure, CSDS-exposed mice had their social interactions with unfamiliar CD1 mice significantly shortened, accompanied by a marked increase in the proportion of c-Fos-positive neurons in the basal forebrain. Fiber photometry recordings suggested that calcium activity in Oxtr⁺ neurons of the basal forebrain was significantly enhanced during social interactions in CSDS mice. Notably, selective deletion of Oxtr in the basal forebrain significantly alleviated CSDS-induced social avoidance and effectively attenuated stress-induced neuronal hyperactivation.

Basal forebrain Oxtr⁺ neurons play a key regulatory role in chronic social defeat stress-induced social avoidance and the processing of social fear-related cues.