摘要
目的 探讨东莨菪碱 (Sco)对吗啡 (Mor)依赖大鼠多巴胺 (DA)系统多巴胺转运蛋白(DAT)及D2 受体的影响。方法 4~ 5月龄SD大鼠 36只 ,随机分为Mor(按体重 2 0mg kg)组、Mor(按体重 2 0mg kg) +Sco组及生理盐水对照组。Mor+Sco组腹腔注射Mor前 15~ 30min先腹腔注射Sco(按体重 1mg kg) ,共给药 8d ;对照组只给予 0 3ml生理盐水。采用两隔室 (C1及C2 )地点偏爱装置测试大鼠的行为学变化。 3组大鼠再各随机均分为 2组 ,分别进行1 2 5I 甲基 3β (4 碘苯基 )托烷 2 β 羧酸酯 (β CIT)、1 2 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。结果 ①Mor组大鼠第 2~ 4天起进入C2室的时间逐渐缩短 ,由第 1天的 (1 6 8± 0 5 7)min降至第 8天的 (0 38± 0 16 )min ;Mor+Sco组大鼠自C1进入C2室的时间第 1天至第 8天略有降低趋势 ,由第 1天的 (1 72± 0 6 9)min降至第 8天的 (1 12± 0 33)min ,第 1天 3组间差异无显著性 (P >0 0 5 ) ,第 8天Mor组及Mor+Sco组均低于对照组 [第 1天 :(1 6 0± 0 5 5 )min ,第 8天 :(1 88± 0 5 4 )min ;t=5 6 82、6 372 ,P均 <0 0 5 ],但Mor+Sco组仍高于Mor组 (t=5 171,P <0 0 5 )。②DAT分布研究示 :Mor组大鼠纹?
Objective To investigate the effect of scopolamine (Sco) on central dopamine transporter (DAT) and D_2 receptor in morphine (Mor) dependent rats. Methods Chronic Mor exposure was induced by repeated Mor (20 mg·kg -1 ·d -1 , i.p.) treatment for 8 d. Conditioned place preference test was used to evaluate the drug seeking behavior. Biodistribution of the imaging agents 125 I-2β-carbomethoxy-3β-(4-iodophenyl)tropane (β-CIT) and 125 I-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethoyl-2-pyrrolidinyl)methyl] benzamide (IBZM) were used to evaluate the central DAT and D_2 receptor during chronic Mor exposure. Results For the Mor plus pretreating with Sco (Mor+Sco) rats, the time for the rats entering C2 from C1 was (1.72±0.69) min in the first day, with little difference from the control and Mor group (P>0.05), and (1.12±0.33) min for the 8th day, still longer than that of the Mor group (t=5.171, P<0.05), but shorter than that of the control group (t=6.372, P<0.05), suggesting that Sco could prevent the trend of drug reinforcement induced by Mor to some extent. The 125 I-β-CIT %ID/g in striatum (ST) and nucleus accumbens (NAC) for Mor+Sco group were 3.307±0.189 and 1.577±0.401 respectively, higher than those of the control group (2.431±0.104, 1.441±0.043, t was 4.151 and 5.416 respectively, P<0.05), but lower than those of the Mor group rats (4.205±0.410, 1.770±0.141, t was 4.871 and 6.922 respectively, P<0.05). The 125 I-IBZM %ID/g in ST, NAC, hippocampus (HIP) and frontal cortex (FC) for Mor+Sco group were 0.589±0.081, 0.683±0.046, 0.175±0.039 and 0.257±0.034 lower than that of the control rats(0.735±0.096, 0.709±0.098, 0.281±0.038, 0.289±0.020, t was 7.841, 6.170, 5.446 and 4.337 respectively, P<0.05), but higher than those of the Mor group (0.540±0.098, 0.640±0.061, 0.140±0.017, 0.232±0.015, t was 6.021, 3.227, 5.113 and 6.174 respectively, P<0.05). Conclusions Sco could prevent the conditioned place preference of the rat induced by Mor, and it was mainly interaction with dopaminergic system. Sco could prevent the hyperfunction of DAT and the down-regulation of D_2 receptor induced by Mor to some extent.
出处
《中华核医学杂志》
CAS
CSCD
北大核心
2004年第3期152-154,共3页
Chinese Journal of Nuclear Medicine
基金
国家自然科学基金资助项目 (30 1 0 0 0 4 4 )
关键词
东莨菪碱
吗啡依赖
脑
多巴胺
转运蛋白
D2受体
大鼠
Morphine
Dependency (psychology)
Scopolamine
Dopamine transporter
Receptors, dopamine D_2
Rats