Effects Of Intracerebroventricular Injection Of BDNF On DRD2,DAT And Their MRNA Expressions In Nucleus Accumbens Septum Of Methamphetamine-dependent Rats

Objective:Establish a methamphetamine-dependent (MA-dependent) rat model, intracerebroventricular injections of brain-derived neurotrophic factor (BDNF) to the MA-dependent rats,observe changes in the nucleus accumbens septum dopamine receptor D2(DRD2) and dopamine transporter (DAT)and their mRNA,and explore the effects of exogenous BDNF interventions on the metabolic function of the nucleus accumbens septum. Methods:160SD rats,were randomly divided into four groups:a control group and three experimental groups that were dependent on one week, four weeks and eight weeks.Stereotypic behavior and conditioned place preference experiments were conducted, After confirming MA dependence, the three experimental groups were injected one week, four weeks and eight weeks respectively to establish different dependence periods for the three groups of rats, Moreover,the three experimental groups were further divided into five subgroups:simple MA-dependent group, MA-dependent+Sham-operated group, MA-dependent+distilled water group, MA-dependent+BDNF low dose intervention group, MA-dependent+BDNF high dose intervention group.Application of immunohisto-chemistry, in situ hybridization, Western blot technology and real-time quantitative PCR detection of the nucleus accumbens DRD2, DAT protein and their mRNA changes.Results:Each groups of MA-dependent DRD2and their mRNA expression in comparison of blank control group were increased, Except for DRD2of eight weeks, the other groups showed a significant difference (P<0.05).Each groups of MA-dependent DAT and their mRNA expression in comparison of blank control group were dropped, there were significant differences (P<0.05). rats of one week and four weeks were given BDNF low and high dose intervention,MA-dependent+BDNF low dose intervention group and MA-dependent+BDNF high dose intervention group DRD2and their mRNA expression level relatively simple MA-dependent group decreased, close blank control group, in comparison of the simple MA-dependent group have a significant difference (P<0.05).One, four, eight weeks the rats were given low and high doses of BDNF intervention, the DAT and their mRNA expression amount MA-dependent+BDNF low dose intervention group,MA-dependent+BDNF high dose intervention group had increased in comparison of MA-dependent group, and blank control group close or even slightly increased, apart from eight weeks group MA-dependent+BDNF low dose intervention group DAT mRNA in comparison of in the simple MA-dependent group no significant significant difference (P>0.05), the rest of each group have significantly with difference (P<0.05).conclusion:1.Multiple intraperitoneal injection of methamphetamine, combined with the conditioned place preference experiments and stereotyped behavior score evaluation method successfully established methamphetamine dependent rats.2.The expression of DRD2and their mRNA in nucleus accumbens septum of MA-dependent rats increased, but the expression of DAT and their mRNA decreased, suggesting that the poisnousness of MA on dopaminergic neurotoxicity.3.Low-dose and high-dose injection of BDNF to MA-dependent rats caused DRD2and their mRNA expression in nucleus accumbens septum decreasing, and DAT and their mRNA expression increasing, suggesting restoration and preservation function of BDNF on the injury of dopaminergic nerve of MA-dependent rats.