The Effects Of Maternal Rats Exposed To Resident Intruder Stress And Baixiangdan Capsule Treatment Before Pregnancy On The Behavior And Neurobiology Of Progeny

Objective:Our aims of this study are to introduce rat model and research evaluative method of anger emotional reaction, to investigate changes of neurotransmitter and hormone and to initially explore the mechanism of rat model as well as effect of medicine.Methods:Model rats with anger emotional reaction before pregnancy are induced by social isolation paradigm plus resident intruder stress, after that we evaluated the model by aggressive behavior test, supplemented by open-field test and sugar preference test, and then intervened with Baixiangdan and Fluoxetine granule. Immediately after the end of the experiment behavior breed offspring, take2-month-old male offspring of rats subsequent into behavioral experiments. after that we evaluated offspring behavioral changes by aggressive behavior test, supplemented by open-field test and elevated plus maze test. Evaluated offspring learning and memory damage by Morris water maze and novel object recognition test. After the end of the experiment behavior, we killed the rats by decapitation, dissected five different brain regions: left prefrontal cortex, left hippocampus, hypothalamus, right prefrontal cortex, right hippocampus. Detected NE, DA,5-HT content in left prefrontal cortex, left hippocampus and hypothalamus by ELISA kit method. The expression level of BDNF P-CREB5-HTT in the right prefrontal cortex and right hippocampus was evaluated by western blot.Result:(1)Aggressive behavior Test results showed:Compared with the drug intervention group scored significantly increased in model group first three weeks after the model of maternal aggressive behavior(P<0.01);Open field test results showed that:Compared with normal control group, the first three weeks after modeling, model group mothers open field test score was significantly higher(P<0.001);Sucrose preference test results showed that:the model group was significantly lower than sucrose water consumption other three groups(P<0.001).(2)Offspring aggressive behavior test results showed:Offspring aggressive behavior in the model group than in normal group scores were significantly increased(P<0.001);Compared with the model group, and Fluoxetine Baixiangdan group attack scored significantly lower(P<0.05, P <0.01). Open field test results show that:the model group offspring open-field experiments total distance than the normal control group was significantly increased(P<0.001);Elevated plus maze test results showed that:the model group than in the control group to enter the open arm percentage was significantly increased(P<0.001), Model group than in the control group the percentage of time of enter the open arms significantly increased (P <0.01), Compared with the model group, the percentage of time into the open arms fluoxetine treatment group significantly reduced (P<0.05).(3) Water maze test results showed that:During space exploration, compared with the normal group, the number of cross platform model rats was significantly reduced(P<0.01);Compared with the model group, the number of platforms through Baixiangdan group and fluoxetine group has gone up, but there was no significant difference(P>0.05). The new object recognition results showed that:Compared with the normal group, distinguish index(DI) of model group was significantly lower(P<0.05). Compared with the model group, DI of Baixiangdan group and fluoxetine group has gone up, but there was no significant difference(P>0.05).(4)ELISA findings:①5-HT:Left hippocampus showed no significant difference (P>0.05) between5-HT levels in each group;A significant reduction in the hypothalamus in the model group compared with the control group(P<0.01);left prefrontal cortex in each group showed no significant difference(P>0.05)②NE:There were no significant differences (P>0.05) between the left hippocampus NE content in each group;NE levels in the hypothalamus of the model group compared with the control group significantly decreased(P<0.05);A significant reduction in the left frontal cortex NE content model group than in the control group(P<0.01), significantly increased(P<0.01)compared with the model group compared NE content in Baixiangdan groups.③) DA:There were no significant differences (P>0.05) between the DA levels in the hypothalamus in each group;A significant reduction in the lef hippocampus DA content model group compared with the control group(P<0.05);Left frontal cortex the DA content of model group compared with the control group was significantly reduced(P<0.001).(5) Western Blot results showed that:①the right hippocampus:Compared with the normal group, the protein expression of BDNF in model group was significantly higher (P<0.001);Compared with the model group, the protein expression of BDNF in Baixiangdan and fluoxetine rats decreased significantly(P<0.05,P<0.001);Compared with the control group, the protein expression of P-CREB relative offspring in model group was significantly higher(P<0.05);compared with the model group, fluoxetine group relative content of rat P-CREB decreased(P<0.01);Compared with the control group, model group offspring5-HTT content were significantly increased relative content(P<0.001);Compared with the model group, and fluoxetine and Baixiangdan5-HTT rats were significantly decreased relative(P<0.001, P<0.001).②Right frontal cortex:Compared with the control group, BDNF levels in the model group rats were significantly increased (P<0.001); compared with the model group, BDNF levels of fluoxetine group were significantly decreased (P<0.01);Brain regions of rats in four groups of P-CREB was no significant difference in the relative content(P>0.05); Compared with the control group, model group offspring5-HTT levels were significantly increased (P<0.001);Compared with the model group, the content of5-HTT in fluoxetine and Baixiangdan group offspring were significantly decreased all (P<0.001).Conclusions:The anger emotional reaction rat model before pregnancy can be induced by the method of social isolation plus resident intruder stress. Modeling method was reliable and mature with a better credibility and repeatability.The effects of maternal rats exposed to resident intruder stress before pregnancy on the behavior and neurobiology of progeny were negative. Mainly showed:aggressive behavior significantly,the ability to adapt to the new environment weakened, tensions increased, lack of ability to experience pleasure, impaired the learning and memory ability. Mechanism of this negative impact may be associated with5-HT monoamine neurotransmitters and expression of BDNF、P-CREB proteins highly correlated.We can assume that Baixiangdan and Fluoxetine granule play the role of pharmacological effects by corrected those indicators and its possible function location may be is different cerebral regions.