Effects of 7,8-Dihydroxyflavone on Spatial Cognitive Function and Synaptic Structure in Schizophrenia Rat Model / 医药导报

ABSTRACT

Objective To investigate the effects of specific TrkB receptor agonist 7,8-dihydroxyflavone ( 7,8-DHF) on spatial cognitive function and synaptic structure in schizophrenia rat model. Methods SD infant rats were divided into normal control group and model group according to the random number table method on the 6th day after birth. During the postnatal day 7 to 11, rats in the normal control group received subcutaneous injection of 0.9% sodium chloride solution (1 mL·kg-1) twice daily, and the rats in the model group were injected with dizocilpine (0.1 mg·kg-1). Beginning on the postnatal day 60, model rats were randomly divided into 7,8-DHF group and model control group, which were given intraperitoneal injection of 7,8-DHF ( 5 mg·kg-1 ) and DMSO once daily for 14 consecutive days, respectively. The rats of normal control group were given equal volume injections of DMSO. Morris water maze task, Golgi staining and Western blotting were adopted to examine spatial cognitive function, hippocampal dendritic spine density, protein expression and activity, respectively. Results The result in the open field test showed that the total travelled distance within 5 min was (12.20±1.62) m in the normal control group, (11.73±1.36) m in the model control group and (12.94±1.09) m in the 7,8-DHF group. The escape latency and travelled distance in the model control group were significantly higher than those in the normal control group (P<0.05), and the escape latency and travelled distance in rats of 7,8-DHF group were significantly shortened as compared with those in the model control group (P<0.05). There was no significant difference in the swimming speed among the three groups (P>0.05). The hippocampal dendritic spine density was (14.2±2.3)/10 μm in the normal control group, (8.0±1.9)/10 μm in the model control group, and (13.5±1.7)/10 μm in the 7,8-DHF group, the differences between the three groups were significant ( all P<0.05);the phosphorylation level of GluR1 protein was (100.0±5.0) in the normal control group, (47.9±10.8) in the model control group, and (97.5±9.3) in the 7,8-DHF group, and the differences among the three groups were significant ( all P<0. 05 ) . Conclusion 7, 8-DHF treatment could improve the spatial cognitive function in rat model of schizophrenia and the mechanisms might be related with the increases of hippocampal dendritic spine density and phosphorylated levels of GluR1.