Abstract:

Objective To investigate the effect of fluoxetine (FLX) on the expression of bromodomain-containing protein 4 (BRD4) in the hippocampus induced by chronic restraint stress (CRS), with the depression-like behaviour also being determined. Methods Twenty-four male Kunming mice were randomly divided into normal saline(NS) group, CRS group and fluoxetine(FLX) intervention(CRS+FLX) group. The mice of the CRS group were subjected to 3 weeks chronic restraint stress. The mice of CRS+FLX group were treated with fluoxetine by intraperitoneal injection 30 minutes before restraint stress from the 8 to 21 days. The mice in the NS group and CRS group were treated with NS. Depression-like behavior was determined by sucrose preference test, sucrose splash test, forced swimming test, novelty object recognition test and open field test. Expression of BRD4 in the hippocampus was determined by Western blotting and Real-time PCR. Results Compared with NS group, mice in the CRS group showed reduced sucrose preference (P<0.01) and decrease the time spent licking in Sucrose splash test (P<0.05) , increase immobility time in the forced swimming test (P<0.01) and decrease on the discrimination ratio in the novelty object recognition test, while FLX treatment effectively reversed the depression-like behavior induced by CRS (P<0.05) Compared with the NS group, CRS led to significantly decreased expression of BRD4 protein and mRNA in the hippocampus (1.000 ± 0.04577 vs 0.08337 ± 0.01658; 1.000 ± 0.04379 vs 0.6672 ± 0.03193, P<0.05), which was attenuated by FLX treatment (0.08337 ± 0.01658 vs 0.4983 ± 0.08574; 0.6672 ± 0.03193 vs 0.8572 ± 0.03181, P<0.05). Conclusion Our finding indicates that FLX could alleviate CRS-induced depression-like behavior in mice, which might be attributed to the increased expression of BRD4 in the hippocampus.

Key words: Fluoxetine, Chronic restraint stress, Depression, Bromodomain-containing protein 4, Hippocampus, Real-time PCR, Mouse