老龄鼠与记忆障碍模型大鼠脑内多巴胺系统的研究

Alteration of CNS dopamine transporter and D 2 receptor in aged and scopolamine induced amnestic rats

目的 从多巴胺 (DA)系统角度探讨实验性记忆障碍及衰老的机制。方法 应用东莨菪碱 (Sco)阻断毒蕈碱 (M)乙酰胆碱受体建立记忆障碍大鼠模型 ,对该模型及老龄鼠进行记忆行为测试 ,并应用12 5I β 甲苯 3 β (4 碘苯基 )托烷 2 β 羧酸酯 (CIT)及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 )脑内分布研究分别探讨在实验性记忆障碍和衰老时脑内DA转运蛋白 (DAT)及D2 受体的变化及其与记忆行为之间的关系。结果 在 10d的记忆测试中 ,第 1天 3组大鼠出错次数无明显差别 ,至第 10天老龄 [(1 3 3± 0 82 )次 /10min]及Sco组大鼠 [(3 0 0± 0 63 )次 /10min]出错次数均明显高于对照组 (t值分别为 5 682、6 3 72 ,P <0 0 5 )。12 5I β CIT脑内分布示Sco组及老龄组在纹状体 (ST)、海马 (HIP)及额叶 (FC)的每克组织百分注射剂量 (%ID/g)均低于对照组 (t值分别为 4 15 1、5 416、4 871、6 92 2、7 3 3 1、3 990 ,P均 <0 0 5 ) ;其中Sco组在FC的 %ID/g低于老龄鼠组 (t=4 13 6,P <0 0 5 )。12 5I IBZM脑内分布示Sco组及老龄鼠在ST的 %ID/g均明显低于对照组 (t值分别为 6 0 2 1和 3 2 2 7,P均 <0 0 5 ) ,且Sco组的HIP、FC的 %ID/g均低于老龄鼠组 (t值分别为

Objective To evaluate the effect of aging and scopolamine (Sco) induced amnesia on central dopamine transporter (DAT), D 2 receptor in rats. Methods The 3 month old amnestic rat models were made by peritoneal injection of the muscarinic receptor antagonist Sco (5 mg/kg) for 10 d. Passive avoidance task was carried out to evaluate the recent learning and memory of rats. The biodistribution of ~ 125I-2-β-carbomethoxy-3-β(4-iodophenyl)-tropan (~ 125I-β-CIT) and ~ 125I-s-3-iodo-N-(1-ethyl-2-pyrolidinyl)methyl-2-hydroxy-6-methoxybenzamide (IBZM) in the brain was used to evaluate the DAT and D 2 receptor. Results During 10 d passive avoidance task testing, no difference was found for the first day among 3 month control, 26 month old and Sco group rats, on the 10th day the entry number of aged and Sco group rats was (1.33±0.82)/10 min, (3.00±0.63)/10 min, respectively, higher than that of the control rats (t was 5.682 and 6.372, respectively,P<0.05). Decreased levels of ~ 125I-β-CIT binding were found in the striatum (ST), hippocampus (HIP) and frontal cortex (FC) of the aged and Sco group rats (t was 4.151,5.416,4.871,6.922,7.331 and 3.990, respectively,P<0.05),the %ID/g of ~ 125I-β-CIT in FC for Sco group rats was lower than that of the old rats (t=4.136, P<0.05). Decreased levels of ~ 125I-IBZM binding in ST was found in both Sco and old rats (t was 6.021 and 3.227, respectively,P<0.05), the %ID/g of Sco group in HIP and FC were lower than that of the old group (t was 4.321 and 7.631, respectively,P<0.05). Conclusions The blockade of M receptor by Sco induced the amnesia of 3 month old rats. The hypodopaminergic function, especially in the DAT and D 2 receptor, was found in ST, HIP and cortex of the aged and Sco group suggesting a gradual degeneration of dopaminergic neurons in aged rats. The decreased levels of ~ 125I-β-CIT and ~ 125I-IBZM binding in cortex area might be responsible for the amnesia in the Sco group through the dopaminergic pathway of midbrain-frontal cortex.