Effects Of Risperidone On The Learning And Memory Functions In Rats With Autism

Objective: To observe the intervention of risperidone on the learning and memory functions of autism offspring model rats established through injected sodium valproate during pregnancy.Methods: The pregnant rats were randomly divided into 3 groups: model group(n=8),control group(n=2)and saline group(n=2).In the model group of pregnant rats,intraperitoneal injection of sodium valproate 600 mg / kg was given to the rats in the second trimester(E12.5d),and at the same time,normal saline groups of pregnant rats were injected intraperitoneally with an equal volume of saline.The offspring of the pregnant rats of control group without any treatment was regarded as normal control group(n=11).The offspring of the pregnant rats that was intraperitoneal injected saline was regarded as normal saline group(NS,n=11).The offspring of the model group of pregnant rats was regarded as the autism model rats.The male rats in model group were randomly divided into 5 groups(n=11 each group): Autism Control group(AS),Autism Normal Saline group(AS+NS),Autism+Risperidone1.0mg/kg group(AS+R1.0mg/kg),Autism+Risperidone 1.58mg/kg group(AS+R1.58mg/kg),and Autism+Risperidone2.5mg/kg group(AS+R2.5mg/kg).At the arranged test times,the weight,the ability of direction inclination,the swimming behavior score,the stereotyped behavior score,the open-field test and the mechanical threshold of the offspring model rats in the following days were detected,and finally the Morris water maze was used to examine the learningand memory functions of rats in all groups.Results:1.The identification of offspring autism model ratsThe weight of rats in Group AS were lower than Group C in P12,P14,P22(P<0.01).The ability of direction inclination of rats in Group AS were lower than Group C in P7-P10(P<0.05).The swimming behavior of rats in Group AS were lower than Group C in P9,P11,P13,P15(P<0.05).The opening time scores of rat eyes in Group AS were lower than Group C in P13-P15(P<0.05).2.The comparisons of 7 groups in stereotyped behavior detection,open-field test,and mechanical threshold resultsKruskal-Wallis analysis of the stereotyped behavior detection of 7 groups showed Group AS+R1.0mg/kg,Group AS+R1.58mg/kg,Group AS+R2.5mg/kg were lower than Group AS,Group AS+NS(P<0.05);Group AS,Group AS+NS were higher than Group C,Group NS(P<0.05).One-way ANOVA analysis of the open-field test of 7 groups showed that Group AS+R1.0mg/kg,Group AS+R1.58mg/kg,Group AS+R2.5mg/kg were higher than Group AS and Group AS+NS(P<0.05),while Group AS and Group AS+NS were lower than Group C and Group NS(P<0.05).Two-way ANOVA(repeated measures)analysis of the mechanical threshold of 7groups showed that Group AS+R1.0mg/kg,Group AS+R1.58mg/kg,and Group AS+R2.5mg/kg were lower than Group AS,and Group AS+NS(P<0.05),while Group AS and Group AS+NS were higher than Group C and Group NS(P<0.05).3.The comparisons of Morris water maze test resultsTwo-way ANOVA(repeated measures)analysis of the escape latency of 7 groups in the place navigation test at 7 days showed F(6,390)=303.024,P<0.01 for test days;F(6,65)=1.480,P>0.05 for animal groups.By the comparisons of SNK-q,Group AS and Group NS were significantly different(P<0.05).Two-way ANOVA(repeated measures)analysis of the swimming speed of 7groups in the place navigation test at 7 days showed F(6,390)=32.951,P<0.01 for test days;F(6,65)=1.656,P>0.05 for animal groups;and F(1,56)=5.389,P<0.01 for the interaction between test days and groups.Chi-square test of the ratio of strategic analysis among rats at 7 days showed?2=176.515,P<0.01 for Day 1,?2=122.970,P <0.01 for Day 2,?2=18.331,P<0.01 for Day 3,?2=69.838,P<0.01 for Day 4,?2= 74.985,P<0.01 for Day 5,?2=78.931,P<0.01 for Day 6,?2=104.246,P< 0.01 for Day 7.Two-way ANOVA analysis of time ratio in target quadrant among 7 groups in the place navigation test at 7 days showed F(6,390)=71.580,P<0.01 for test days,F(6,65)=2.286,P<0.05 for animal groups.The comparison of the number of crossing plate at the 8th test day showed,F=0.984,P>0.05,in the spatial probe test.Conclusions: Through detecting the weight,the ability of direction inclination,the swimming behavior score and so on,we can conclude that the animal model is established successfully.The learning and memory functions of model rats are damaged in model rats with autism.Risperidone can alleviate stereotyped behavior and the sensitivity to pain of model rats.Risperidone may also have an effect on the learning and memory functions of model rats to some extent.