Objective MicroRNAs (miRNAs) are a large family of small non-coding RNAs which negatively control gene expression at both the mRNA and protein levels.The number of miRNAs identified is growing rapidly and approximately one-third is expressed in the brain where they have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse plasticity.It has been proposed that miRNAs may have important roles in complex psychiatric disorders.Pharmacological and behavioral data have posited miR-16 as a central effector that regulates SERT expression and mediates the adaptive response of serotonergic and noradrenergic neurons to antidepressants treatment.Until now, little has been known about the potential involvement of hippocampal miRNAs in depression.Methods Male Sprague-Dawley rats were subjected to a sequence of 12 different stressors (two per day) for 35 d.Sucrose preference test was used to assess rats depressive-like hehavior.MiRNA expression profiling was identified by using Solexa sequencing.Lists of predicted effectors of candidate miRNAs were generated using the TargetScan program (http://www.targetscan.org).Results (1) One miRNA (miR-1224) showed a significant variation with fold change higher than 2.0 and four miRNAs showed decrease (miR-1249, 182, 183, 204).(2) Brain-derived neurotrophic factor (BDNF) and CLOCK gene, which have been reported an association with depression, are two predicted miR-182 target sites.Conclusion miR-182 maybe an important molecular regulator that control the complex actions of chronic stress in hippocampus and the neuroadaptations associated with depression.