The involvement of P2X4R is further examined using ivermectin (IVM), a selective P2X4R agonist.<h4>Results</h4>LIPUS significantly alleviates the LPS-induced depression-like behavior, suppresses hippocampal pro-inflammatory cytokine expression, inhibits microglial activation, and reduces neuronal apoptosis. The gene discussed is P2RX4; the disease is depressive disorder.