Retigabine alleviates chronic restraint stress-induced memory retrieval impairment in male mice

来源 :中国药理学会第十三次全国学术大会 | 被引量 : 0次 | 上传用户:lflhzq
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  Aim To investigate whether Kv7 channels opener retigabine could alleviate memory impairment induced by chronic restraint stress (CRS) and the underlying neuroprotective mechanisms.Methods Adult male Kunming(KM) mice, weighing 20 ~25 g, were restrained in wellventilated Plexiglass tubes for 6 h daily beginning from 10: 00 to 16 : 00 for 21 consecutive days.Mice were injected with retigabine (10 mg· kg1) or vehicle (10% DMSO) 30 min before restraint stress for 21 days.After stressor cessation, the spatial learning and memory was determined by Morris water maze test, the levels of pAkt, pGSK3β and pErk1/2 of hippocampal tissues were examined by western blot.Results Compared with control group, CRS mice exhibited significantly longer escape latencies on day 2, 3 and 4 (P <0.05, P <0.01, P <0.01) respectively, but retigabine (10 mg · kg1) treatment had no influences on escape latencies compared with CRS group.During the probe test, CRS mice spent significant less time in target quadrant than control group (P <0.01).Compared with CRS group, retigabine (10 mg · kg1)treatment increased the time spent in target quadrant (P <0.01).Additionally, the swimming speed showed no significant differences among groups.Western blot results showed that the levels of pAkt, pGSK3β and pErk1/2 in the hippocampus of CRS mice were significantly decreased compared with control group.Compared with CRS group, retigabine (10 mg· kg1) treatment strongly prevented the reduction of pAkt and pGSK3β (P < 0.01),but had no effect on the reduction of pErk1/2.Conclusion Retigabine protected against CRSinduced spatial memory retrieval impairment partly via activation of Akt/GSK3β signaling pathway.
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