Expression Of Dopamine Transporter, Dopamine Receptor D1, Dopamine Receptor D2, And Serotonin Transporter In Six Cerebral Regions Related To Methamphetamine Dependence In Rats

Objective:To establish a rat model of methamphetamine(MA)dependence,then detect the expression of dopamine transporter(DAT),dopamine receptor D 1(DRD1), dopamine receptor D2(DRD2),and serotonin transporter(SERT)in six cerebral regions which related to MA dependence.Then investigate the correlation between the expression of DAT,DRD1,DRD2 and SEPT with the mechanism of MA dependence.Methods:The rats were devided into five groups which were control group,1 week group,2 weeks group,4 weeks group,and 8 weeks group of MA dependence.The models of diffenrent periods of administered MA(ip,10mg.kg-1 per day)were established.Then observe the stereotyped behavior and do experiment of conditioned position preference(CPP)to confirm the models were successfully esablished.The animals were sacrificed,the brain tissues of the prefrontal cortex, nucleus accumbens septum,striatum,hippocampus,ventral tegmental area,and substantia nigra were collected to detect the expression of DAT,DRD1,DRD1,SERT with the methods of immunohistochemistry,in situ hybridization,western blotting, and the reversed transcriptive polymerase chain reaction(RT-PCR).Results: Compared to control group,the score of stereotyped behavior and CPP of four dependent groups had significant difference(P＜0.05).There were positive expression in all six regions with DAT,DRD1,DRD2,and SERT.Compared to the same cerebral region in different groups,the expression of DAT,DRD1,DRD2,and SEPT were difference(P＜0.05).At frontal cortex,the DAT decreased in 1 week,increased in 2 weeks and continuous to 4 weeks,then decreased in 8 weeks.There was significant differnce that compared cotrol group with 1,2,8 weeks group,4 weeks with 8 weeks group(P＜0.05 ).The DRD1 decreased in 1 week,increased in 2 weeks and continuous to 4 weeks,then decreased in 8 weeks.There was significant differnce that compared cotrol group with 1,4 weeks group.The DRD2 were increased in 1 week,then decreased in 2 weeks and continuous to 4 weeks,then increased again in 8 weeks. There was significant diffemce that compared cotrol group with 1,2,8 weeks group, 1 week with 4 weeks group,4 weeks with 8 weeks group(P＜0.05).The SERT decreased in 1 week and continuous to 2 weeks,then increased in 4 weeks,decresed again in 8 weeks.There was significant differnce that compared cotrol group with 1,2 weeks group(P＜0.05).At nucleus accumbens septum,the DAT decreased in 1 week and continuous to 2 weeks,increased in 4 weeks,then decreased again in 8 weeks. There was significant differnce that compared cotrol group with 1,2,8 weeks group, 1 week with 4 weeks group,2week with 4 weeks and 8 weeks group(P＜0.05).The DRD1 increased from 1 week to 8 weeks.There was no significant differnce that compared cotrol group with four dependent groups.The DRD2 increased in 1 week and continuous to 2 weeks,then decreased in 4 weeks and increased again in 8 weeks. There was significant diffemce that compared cotrol group with 1,2,8 weeks group, 4 weeks with 8 weeks group(P＜0.05).The SERT decreased in 1 week and continuous to 2 weeks,then increased in 4 weeks,decreased again in 8 weeks.There was significant differnce that compared cotrol group with 1,2 weeks group,1 week with 4 weeks and 8 weeks group,2 week with 4 weeks and 8 weeks group(P＜0.05). At striatum,the DAT decreased in 1 week,then increased in 2 weeks and continuous to 4 weeks,decreased again in 8 weeks.There was significant differnce that compared cotrol group with 1,2,8 weeks group(P＜0.05).The DRD1 decreased from 1 week to 8 weeks.There was no significant differnce that compared cotrol group with four dependent groups.The DRD2 increased in 1 week and continuous to 2 weeks,then decreased till 8 weeks.There was significant differnce that compared cotrol group with 1,2 weeks group(P＜0.05).The SERT decreased from 1 week to 2 weeks,then increased in 4 weeks and decreased again in 8 weeks.There was significant differnce that compared cotrol group with 2,4,8 weeks group,1 week with 2 weeks group(P＜0.05).At hippocampus,the DAT and DRD1 increased in 1 week,then decreased from 2 weeks to 4 weeks,increased again in 8 weeks.There was no significant differnce that compared cotrol group with four dependent groups.The DRD2 decreased in 1 week,then increased from 2 weeks to 8 weeks.There was significant differnce that compared cotrol group with 1,2,4,8 weeks group(P＜0.05 ).The SERT decreased from 1 week to 2 weeks,increased in 4 weeks and decreased in 8 weeks. There was significant differnce that compared cotrol group with 2 weeks group,1 week group with 2 weeks group,2 weeks with 1,4 weeks group(P＜0.05).At ventral tegmental area,the DAT increased from 1 week to 8 weeks.There was significant differnce that compared cotrol group with 4,8 weeks group(P＜0.05).The DRD1 increased from 1 week to 4 weeks,then decreased in 8 weeks.There was no significant differnce that compared cotrol group with four dependent groups.The DRD2 increased from 1 week to 2 weeks,then decreased from 4 weeks to 8 weeks. There was significant differnce that compared cotrol group with 2 weeks group(P＜0.05 ).The SERT decreased in 1 week,then increased in 2 weeks and decreased from 4 weeks to 8 weeks again.There was significant differnce that compared cotrol group with 1,4,8 weeks group,2 weeks group with 4 weeks and 8 weeks group(P＜0.05). At substantia nigra,the DAT decreased in 1 week,then increased in 2 weeks, decreased from 4 to 8 weeks.There was significant differnce that compared 2 weeks group with 4,8 weeks group(P＜0.05).The DRD1 increased in 1 week and decreased in 2 weeks,then increased from 4 to 8 weeks.There was no significant differnce that compared cotrol group with four dependent groups.The DRD2 increased in 1 week and decreased from 2 to 4 weeks,then increased again in 8 weeks.There was no significant differnce that compared cotrol group with four dependent groups.The SERT decreased from 1 to 2 weeks,increased in 4 weeks and decreased again in 8 weeks.There was significant differnce that compared cotrol group with 1,2,4,8 weeks group(P＜0.05).Compared to the six different regions in same experiment group,the DAT,DRD1,DRD2,and SERT also had different changes,and had significant difference at several cerebral regions(P＜0.05).Conclusion:1.the rat model of MA dependence can be established succussfully that use the method of multi-administer MA and comfirm with experiment of CPP.2.at frontal cortex, nucleus accumbens septum,striatum,hippocampus,ventral tegrnental area,and substantia nigra,the expression of DAT,DRD1,DRD2,and SERT had significant diffenence,which related to the different cerebral regions and the time course of administered MA.The changes of DAT,DRD1,DRD2,and SERT may play a crucial role in MA dependece.