In our study, a significant increase in ASCT2 expression in the hippocampus, especially in the CA1 and CA3 regions, followed CSDS; whereas ASCT2 knockdown alleviated social avoidance and behavioral despair induced by CSDS, demonstrating the direct contribution of hippocampal ASCT2 to depression-like behavior. This evidence concerns the gene SLC1A5 and depressive disorder.