Effect of agomelatine on memory impairment and ERK5 expression in hippocampus of rats with posttraumatic stress disorder

Abstract

Objective To investigate the effect of agomelatine on memory impairment and expression of extracellular signal-regulated kinase 5 (ERK5) in post-traumatic stress disorder (PTSD)-like rats. Methods Forty-eight SD rats were divided into control group (SHAM group), post-traumatic stress disorder group (PTSD group), agomelatine group (AGO group) and placebo control group(PC group) according to random number table with 12 in each group. The PTSD-like model was established by internationally recognized single prolonged stress (SPS) stimulation, and the AGO group and PC group were given the same amount of agomelatine and saline respectively by intragastric administration within 8 hours after modeling for 14 days. The arousal emotional level and learning and memory ability of rats were observed by open field experiment and Morris water maze test. Then the expressions of ERK5 and ERK5 mRNA in hippocampus of rats were detected by Western blot and qRT-PCR. Results (1) The results of the open field experiment showed that compared with the SHAM group (38.58±5.76), the numbers of crossing the grids of the PTSD group (29.75±3.75) decreased (P<0.01). Compared with the PC group (28.58±2.91), the number of crossing the grids of the AGO group (41.00±4.49) increased (P<0.01). (2) In Morris water maze test, positioning navigation experiment showed that compared with the SHAM group, the escape latency of the PTSD group and the PC group increased (P<0.01), while the escape latency of AGO group was shorter than that of the PC group (P<0.01). And in the space exploration experiment, compared with the SHAM group (2.12±0.51), the times of crossing the platform in PTSD group (1.03±0.43) and the PC group (1.23±0.59) decreased (P<0.01), while the times of crossing the platform in AGO group (2.75±0.72) increased compared with PC group (P<0.01). Compared with SHAM group (12.14±2.53), the latency of crossing the platform of PTSD group (27.33±6.54) increased (P<0.01), and the agomelatine group (14.36±4.27) decreased compared with the PC group (29.67±9.72) (P<0.01). (3) Results of Western blot and qRT-PCR showed compared with the SHAM group, the levels of ERK5 and ERK5 mRNA in rat hippocampus were up-regulated in the PTSD group (P<0.01), and the expression of ERK5 and ERK5 mRNA was higher than that of PC group (P<0.01). Conclusion Agomelatine can effectively improve the learning and memory ability of PTSD-like rats, which may be related to the up-regulation of ERK5 protein expression in hippocampal tissues. Key words: Agomelatine; Post-traumatic stress disorder; Extracellular signal-regulated kinase 5; Rats