吗啡依赖大鼠脑多巴胺转运蛋白及D_2受体的研究

Exploration of dopamine transporter and D_2 receptors in morphine dependent rats through ^(125)I-β-CIT、^(125)I-IBZM cerebral autoradiography and the biodistribution study

目的 观察吗啡依赖 (MD)大鼠脑多巴胺 (DA)系统的变化。方法 采用两隔室 (C1及C2 )模型训练大鼠对吗啡产生条件性位置偏爱 ,造成MD大鼠模型 ,用DA转运蛋白 (DAT)及DAD2 受体显像剂12 5I 甲苯 3β (4 碘苯基 )托烷 2 β 羟酸酯 (β CIT)、12 5I 左旋 3 碘 2 羟基 6 甲氧基 N[(1 乙基 2 吡咯烷 )甲基 ]苯酰胺 (IBZM)脑放射自显影、脑内放射性分布观察MD及对照组大鼠脑内D2 受体及DAT的变化。结果 条件性位置偏爱实验自第 6d后MD组大鼠由C1进入C2时间平均 (0 84±0 5 0 )min ,与对照组 (2 .40± 1.10 )min比较差异有显著性 (P <0 .0 5 ) ;放射自显影图像分析示 :12 5I β CITMD组纹状体 (ST) /小脑 (CB)及伏隔核 (NAC) /CB摄取比值分别为 4.76± 0 .92、2 .72± 0 96 ,与对照组 (5 .92± 0 .6 7、4.16± 0 .5 6 )比较差异有显著性 (P <0 .0 5 ) ;12 5I IBZM在MD组的ST/CB和NAC/CB摄取比值分别为 4.11± 0 .5 6、2 .6 4± 0 .2 5 ,明显低于对照组 (5 .43± 0 .74、3.49± 0 .6 5 ,P <0 0 5 ) ,脑内分布研究 (%ID/g脑组织湿重 )也证实MD组12 5I β CIT、12 5I IBZMST/CB摄取比值分别比对照组降低(2 1 6 8± 11.11) %和 (18.6 9± 9.97) %。结论 应用12 5I β CIT、12 5I IBZM能够敏感地反映MD?

Objective To explore the variation of cerebral dopamine(DA) transmiting system in morphine dependent(MD) rats using dopamine transporter(DAT) and D 2 receptors imaging agent. Methods MD model rats were established by using a two compartment(C1 and C2 morphine conditioned compartment) apparatus for assessing morphine conditioned place preferences in rats. 125 I 2β carbomethoxy 3β (4 iodophenyl)tropane( 125 I β CIT) and 125 I 3 iodo 2 hydroxy 6 methoxy N [(1 ethyl 2 pyrrolidinyl)methyl] benzamide ( 125 I IBZM) cerebral DAT and D 2 receptor autoradiography and biodistribution study were used to evaluate the variation of DAT and D 2 receptors in morphine dependent rats. Results The mean time of MD rats entering from C1 to C2 was (0.84±0 50) min after 6 days' conditioned place preference training, shorter than that of the control group[(2.40±1 10) min, P <0.05]. Autoradiographic analysis showed that 125 I β CIT uptake ratio of striatum (ST)/cerebellum(CB) and nucleus acumbens(NAC)/CB in MD group were 4.76±0.92 and 2.72±0.96,significantly lower than that of control group(5.92±0.67 and 4.16±0.56, P <0.05);the ST/CB and NAC/CB of 125 I IBZM uptake ratio in MD group were 4.11±0.56 and 2.64±0.25,lower than that in control group(5.43±0.74 and 3.49±0.65, P <0.05). The 125 I β CIT、 125 I IBZM biodistribution study also showed that the DAT and D 2 binding sites were reduced in ST of MD group by (21.68±11.11)% and (18.69±9.97)% comparing to the controls, respectively. Conclusions The DAT and D 2 receptors in both ST and NAC were all involved and reduced to some extent in morphine dependent model rats, the DAT and D 2 receptor imaging agent could reflect the variation of DAT and D 2 receptors, this would afford the theoretical basis for D 2 receptors and DAT imaging in study on preventing drug addiction and on its abstinence.