Intracerebroventricular Injection Of GDNF To Induce DRD2.DAT And Its MRNA Expressions In Methamphetamine Dependent Rats’ Nucleus Accumbens Septum

Objective:To establish methamphetamine (MA) dependent rats Models,observe dopamine D2receptor (DRD2) and dopamine transporter (DAT) changes of MA depend ent rats and that of after intracerebroventricular injection of glial cell line-derived trophic factor (GDNF) in nucleus accumbens septum, then explore the impact function metabolic changes of exogenous GDNF intervention on MA dependent rats. Methods:160SD rats were randomly divided into control group,1week group,4weeks group and8weeks group of MA dependence,three experimental groups were divided into five subgroups:simplex MA dependent group,MA dependent+sham group,MA dependent+distilled water group, MA dependent+low-dose GDNF intervention group and MA dependent+high-dose GDNF intervention group.To detect the changes of DRD2,DAT protein and its mRNA in nucleus accumbens septum with the methods of immunohistochemistry,in situ hybridization,Western blot technology and real-time quantitative PCR. Results:1.Compared with the control group, conditioned place preference experiment of the three simplex methamphetamine dependence groups were significant differences,proved that methamphetamine dependent rat models successfully established.2.Compared with the control group, three different subgroups within the experimental group, the DRD2,DAT protein and its mRNA expression in nucleus accumbens septum have changed.The expression of DRD2and its mRNA in simplex MA dependent groups, MA dependent+sham group, MA dependent+distilled water group were increased, while the expression in MA dependent+low-dose GDNF intervention group and MA dependent+high-dose GDNF intervention group were decreased; The expression of DAT and its mRNA in simplex MA dependent groups, MA dependent+sham group, MA dependent+distilled water group were decreased, while the expression in MA dependent+low-dose GDNF intervention group and MA dependent+high-dose GDNF intervention group were rebounded significantly.Conclusion:1.The establishment of of a successful methamphetamine dependent rat models using repeated intraperitoneal injection of methamphetamine, combined with the CPP experiment.2.GDNF can change the expression of DRD2and DAT and its mRNA in MA dependent rats’nucleus accumbens septum,suggesting that GDNF have a therapeutic effect on toxic effects of methamphetamine.3.GDNF can improve expression changes of DRD2and DAT and its mRNA due to methamphetamine both in0.5μg/μl and1.0μg/μl and the effect is better in0.5μg/μl.