Growing evidence has suggested that alterations in the synaptic proteins (for instance, PSD-95 and GluA1) and dendritic spine density after social defeat stress have a role in the depression-like phenotype and that the recovery of synaptogenesis by antidepressants has a key role in their antidepressant actions.41, 42, 43, 47, 48, 49 Intravenous injection of MR16-1 showed a robust antidepressant effect by normalizing decreased levels of PSD-95 and GluA1 in the hippocampus and PFC and increased levels of PSD-95 and GluA1 in the NAc. This evidence concerns the gene DLG4 and major depressive disorder.