Abstract: OBJECTIVE: To investigate the antidepressant mechanism of acupuncture at the molecular level in the pituitary gland of rats exposed to chronic restraint stress(CRS).METHODS: Forty-eight rats were randomly divided into a control group(C), model group(M), fluoxetine group(F), and acupuncture group(A). CRS was induced in the model group by restraining rats for 28 days. Groups F and A were given fluoxetine administration and acupuncture intervention, respectively, 1 h before the CRS procedures were implemented. On the 29 th day, rat pituitary glands were harvested for RNA extraction and RNA-sequencing analysis.RESULTS: Differentially expressed gene analysis identified 148, 87, and 179 response genes differen-tially expressed in group C vs group M, group F vs group M, and group A vs group M, respectively. Using Gene Ontology term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, we identified the up-regulation of gene sets involved in extracellular space,receptor binding, and monoamine neurotransmitter metabolism, and the down-regulation of gene sets involved in immune response and inflammatory response as the prevailing transcriptomic signatures in the pituitary gland of rats treated with CRS,fluoxetine, or acupuncture.CONCLUSION: Our findings suggest that acupuncture has a multitarget antidepressant effect at the molecular and behavioral levels.

Key words: Acupuncture, Depression, Pituitary gland, Gene ontology, RNA, Behavior