Expression Of Glutamate Receptors And Glutamate Transporter In Six Cerebral Regions Related To Methamphetamine Dependence In Rats After Gastrodin Intervention

Objective:To establish rat model of methamphetamine dependence,then the animals were intervened with gastrodin,to detect the expression of Glutamate receptors(Grin2B、Glur-1)、Glutamate transporter(GLT-1、EAAT-1)and Caspase-3 in six cerebral regions related to MA dependence,which were frontal cortex(FC),striatum(CPu),nucleus accumbens septi(NAc),hippocampus(HP),substantia nigra(SN),and ventral tegmental area(VTA).Then the dependent mechanism of MA and the effects of gastrodin on the neurotoxicity damages induced by MA were investigated.Methods:80 SD rats were randomly divided into groups of 6 weeks and 8 weeks,according to the time.Each group can be further divided into five groups:normal saline group(NS),the preintervention of gastrodin group,MA dependent group,gastrodin intervention group(10mg),gastrodin intervention group(20mg).The methamphetamine-dependent rat model was established by intraperitoneal injection of methamphetamine,and the behavioral changes were observed by conditional preference test(CPP)and stereotyped behavioral scores.After confirming the generation of methamphetamine in rats,the dependent model was established at different time intervals and then treated with gastrodin.The expression of Glutamate receptors(Grin2B、Glur-1),Glutamate transporter(GLT-1、EAAT-1)and Caspase-3 in different brain regions were detected by immunofluorescence,Western blotting and real-time quantitative PCR.Results:1.Compared with the control group,the scores of stereotyped behavior and CPP of MA dependent groups had significant difference,which means t he rat model of methamphetamine dependence was established.2.The expressio n of Caspase-3,NR2B of 8weeks,Glur-1 of most cerebral region,GLT-1 and EAAT-1 of 8 weeks increased after administration of MA,while the expression of Glutamate transporter(GLT-1、EAAT-1)decreased.3.The residence time in the drug-combined box was significantly shortened after the intervention of gastrodin.The stereotyped behavior score was also significantly decreased after the intervention of gastrodin.4.The increased level of Glutamate receptors(G rin2B、Glur-1),Glutamate transporter(GLT-1、EAAT-1)and Caspase-3 cause d by MA can be decreased by Gastrodin.We also find that therapeutic effect o f 20mg was better than lOmg.Conclusion:l.The rat model of MA dependence was established successfully by using the method ofintraperitoneal injection MA,observing the conditioned place preference(CPP)andstereotyped behavior(SB).2.The expression of Caspase-3,NR2B of 8weeks,Glur-1 of most cerebral region,GLT-1 and EAAT-1 of 8 weeks increased after administration of MA,while the expression of Glutamate transporter(GLT-1、EAAT-1)decreased.They might have an intimate correlation with the mechanism of MA dependence and neurotoxicity.3.The increased level of Glutamate receptors(Grin2B、Glur-1)、Glutamate transporter(GLT-1、EAAT-1)and Caspase-3 caused by MA can be decreased by Gastrodin,and therapeutic effect of 20mg was better than lOmg.The data indicated that gastrodin might have a protective effect on the neurotoxicity induced by MA.