Effect of agomelatine on memory impairment and ERK5 expression in hippocampus of rats with posttraumatic stress disorder / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the effect of agomelatine on memory impairment and expres-sion 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 recog-nized single prolonged stress (SPS) stimulation,and the AGO group and PC group were given the same a-mount 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 ex-periment 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) de-creased 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 tis-sues.