Expression Of 5-hydroxytryptamine Receptor 1A And 5-hydroxytryptamine Receptor 2A On Six Cerebral Regions Related To Methamphetamine Dependent Rat After Gastrodin Intervention

OBJECTIVE:To establish a methamphetamine(MA)dependent rat model,the expression of 5-hydroxytryptamine receptor-lA(5-HT 1A)and 5-hydroxytryptaminereceptor-2A(5-HT 2A)in six brain regions,which were nucleus accumbens septi,striatum,hippocampus,frontal cortex,ventral tegmental area,and substantia nigra,were detected.Then two dosages of gastrodin were administrated to the MA dependent rats,and the expression of 5-HT1A and 5-HT2A were measured.And the protective or therapeutic effect of gastrodin on MA induced injury of central nervous system and the mechanism were discussed.METHODS:Eighty SD rats were randomly divided into 2 groups,i.e MA dependent 2 weeks group and MA dependent 4 weeks group.Each group had 5 sub-groups(n=8),which were saline control group(NS),MA dependent group(2 weeks or 4 weeks),the gastrodin pre-intervention group,gastrodin intervention group(10mg),gastrodin intervention group(20mg).And for the gastrodin intervention group,the time period of gastrodin injection was 4 weeks.The methamphetamine-dependent rat model was established by intraperitoneal inject methamphetamine,and the conditioned preference test(CPP)and stereotyped behavioral scores were observed.After the methamphetamine dependence rat model was confirmed,the MA dependent groups of different time intervals were established,those were MA dependent 2 weeks group and MA dependent 2 weeks group.And then,different dosages of gastrodin were treated.The expression of 5-HT 1A and 5-HT 2A in six different cerebral regions of central nerve system were detected by immunofluorescence,Western blotting and real-time quantitative PCR.RESULTS:1.Behavioral tests:Compared with the NS group,the results of conditioned preference test of the MA-dependent group was significant difference(P<0.05),which indicated the methamphetamine-dependent model was successfully established.2.Morphology:Expression of 5-HT 1A and 5-HT 2A were located at nucleus at the frontal cortex,hippocampus,striatum,and nucleus accumbens septi.And 5-HT 1A and 5-HT 2A also expressed at the membrane and cytoplasm at ventral tegmental area and substantia nigra.3.The expression of 5-HT 1A and 5-HT 2A:at most cerebral regions,5-HT 1A and 5-HT 2A were decreased after administration of MA dependent 2 weeks group and MA dependent 42 weeks group.And after administrating different dosages of gastrodin,the expressions of 5-HT 1A and 5-HT 2A were increased.The data indicated that expression of 5-HT 1A and 5-HT 2A might have a crucial correlation with the mechanism of MA dependence and neurotoxicity,and gastrodin might have a protective effect on the neurotoxicity induced by MA.CONCLUSION:1.the methamphetamine-dependent rat model was established successfully via the method of intraperitoneal injection MA and measured with the CPP test.2.The expression levels of 5-HT-1A and 5-HT-2A in nucleus accumbens septi,striatum,hippocampus,frontal cortex,ventral tegmental area,and substantia nigra were different.The data suggest that 5-HT 1A/2A might involve in the mechanism of methamphetamine-induced neurotoxicity.3.The data suggest that gastrodin might be a potential drug for the treatment of MA dependence.