杏仁核和扣带回毁损对甲基苯丙胺大鼠边缘区多巴胺受体的影响

目的　探讨立体定向杏仁核和扣带回的联合毁损对甲基苯丙胺 (MAP)大鼠脑内边缘区多巴胺D2受体表达的影响。方法　 4 0只SD大鼠随机分为对照组、MAP组、MAP加毁损组和MAP加假毁损组 ,每组各 10只 ;采用经腹腔注射MAP制备精神分裂症MAP模型 ,立体定向 射频毁损杏仁核和扣带回 ,免疫组织化学ABC法观察边缘区D2受体的表达。结果　与对照组比较 ,MAP组及MAP加假毁损组大鼠边缘区D2受体表达有非常显著性差异(P <0 0 1) ;MAP加毁损组大鼠边缘区D2受体阳性细胞数目与对照组比较无显著性差异 (P <0 0 1)。结论　杏仁核和扣带回的联合毁损可以抑制使用MAP而诱发的边缘区D2表达的亢进。     

伏隔核毁损对MAP模型大鼠行为及脑内DA受体的影响

目的 探讨立体定向伏隔核毁损对甲基苯丙胺（MAP）模型大鼠行为学及不同脑区多巴胺D2受体表达的影响。方法 将80只SD大鼠随机分为对照组、模型组、假手术组和手术组，每组各20只。经腹腔注射MAP制备精神分裂症模型，采用立体定向一直流电毁损伏隔核，观察大鼠刻板行为变化；并采用原位杂交法观察额叶、颞叶、边缘区及脑干部位的D2受体表达。结果 与对照组比较，模型组及假手术组大鼠刻板行为评分及各个脑区D2受体表达均显著性增加；与模型组及假手术组比较，手术组大鼠刻板行为评分及各脑区DA受体阳性细胞数目均显著性减少。结论 伏隔核毁损可能通过抑制MAP诱发的脑内D2表达亢进而改变其行为学异常。     

杏仁核和扣带回联合毁损对MAP大鼠脑内多巴胺D2受体的影响

目的探讨联合毁损杏仁核和扣带回对甲基苯丙胺(M AP)大鼠脑内边缘区多巴胺D2受体表达的影响。方法40只SD大鼠随机分为对照组、M AP组、M AP 毁损组和M AP 假毁损组,每组各10只;采用经腹腔注射M AP制备精神分裂症M AP模型,立体定向-射频毁损杏仁核和扣带回,免疫组织化学ABC法观察边缘区D2受体的表达。结果与对照组和M AP 损毁组比较,M AP组及M AP 假毁损组大鼠边缘区D2受体表达有显著性差异(P<0.01);M AP 毁损组大鼠边缘区D2受体阳性细胞率与对照组比较差异无显著性(P>0.05)。结论杏仁核和扣带回的联合毁损可抑制使用M A P诱发的边缘区D2受体表达的亢进。     

伏隔核毁损对MAP模型大鼠行为及脑内DA受体影响的研究

目的探讨立体定向伏隔核毁损对甲基苯丙胺(MAP)模型大鼠行为学及不同脑区多巴胺D2受体表达的影响。方法80只SpraqueDawley(SD)大鼠随即分为对照组、模型组、假手术组和手术组,每组各20只;采用经腹腔注射MAP制备精神分裂症模型,立体定向-直流电毁损伏隔核,观察大鼠刻板行为变化,原位杂交法观察额叶、颞叶、边缘区及脑干部位D2受体表达。结果与对照组比较,模型组及假手术组大鼠刻板行为评分及各个脑区D2受体表达均显著增加;而与模型组及假手术组比较,手术组大鼠刻板行为评分及各脑区DA受体阳性细胞数目均显著减少。结论伏隔核毁损可能是通过抑制使用MAP而诱发的脑内D2表达的亢进而改变其行为学的异常。     

扣带回毁损对甲基苯丙胺大鼠颞叶皮质多巴胺D2受体的影响

目的探讨扣带回立体定向毁损对甲基苯丙胺(MAP)大鼠脑内颞叶皮质多巴胺D2受体表达的影响.方法80只SD大鼠随机分为对照组、MAP组、MAP 毁损组和MAP 假毁损组,每组各20只;采用经腹腔注射MAP制备精神分裂症MAP模型,立体定向-射频毁损扣带回,免疫组织化学ABC法观察颞叶皮质D2受体的表达.结果与对照组比较,MAP组及MAP 假毁损组大鼠颞叶皮质D2受体表达差异有显著性(P＜0.01);MAP 毁损组大鼠颞叶皮质DA受体阳性细胞数目与对照组比较差异无显著性(P＞0.05).结论扣带回毁损可以抑制使用MAP而诱发的颢叶皮质D2表达的亢进.     

扣带回毁损对甲基苯丙胺大鼠颞叶皮质多巴胺D2受体的影响

目的探讨扣带回立体定向毁损对甲基苯丙胺(MAP)大鼠脑内颞叶皮质多巴胺D2受体表达的影响。方法80只SD大鼠随机分为对照组、MAP组、MAP 毁损组和MAP 假毁损组,每组各20只;采用经腹腔注射MAP制备精神分裂症MAP模型,立体定向-射频毁损扣带回,免疫组织化学ABC法观察颞叶皮质D2受体的表达。结果与对照组比较,MAP组及MAP 假毁损组大鼠颞叶皮质D2受体表达差异有显著性(P<0.01);MAP 毁损组大鼠颞叶皮质DA受体阳性细胞数目与对照组比较差异无显著性(P>0.05)。结论扣带回毁损可以抑制使用MAP而诱发的颞叶皮质D2表达的亢进。     

基底外侧杏仁核和隔内侧核毁损对精神分裂症大鼠行为学及中脑D2受体的影响

目的 探讨立体定向基底外侧杏仁核(BLN)和隔内侧核(MS)的联合毁损对甲基苯丙胺(MAP)大鼠中脑脑区多巴胺D2受体(D2DR)表达的影响.方法 48只SD大鼠随机分为对照组、模型组、假手术组、基底外侧杏仁核毁损组(BLN组)、隔内侧核毁损组(MS组)、基底外侧杏仁核与隔内侧核联合毁损组(BLN MS组),每组各8只;采用经腹腔注射MAP制备精神分裂症MAP模型,立体定向--直流电毁损BLN和MS,原位杂交法观察中脑脑区D2DR的表达.结果 与对照组比较,模型组及假手术组大鼠中脑D2DR表达有非常显著性差异(P<0.01); BLN组、MS组及(BLN MS)组中脑D2DR阳性细胞数目与显著低于模型组(P<0.01).结论 BLN和MS的联合毁损可以抑制使用MAP而诱发的中脑D2DR表达的亢进.     

杏仁核毁损对甲基苯丙胺大鼠脑内5-HT2A受体的影响

目的探讨杏仁核毁损对甲基苯丙胺（MAP）大鼠脑内5-HT2A受体表达的影响。方法24只SD大鼠分为对照组、模型组、假手术组和手术组，每组各6只；采用腹腔注射MAP制备精神分裂症模型，立体定向毁损杏仁核，采用Sams-Dodd法评定各组动物刻板行为的变化，以PCR技术测定脑组织中5-HT2A受体mRNA的表达。结果杏仁核毁损可明显降低MAP大鼠刻板行为评分（P〈0．05）。各组大鼠额叶、颞叶皮质和中脑均有5-HT2A受体mNRA（61lbp）的阳性表达，且均以额叶皮质表达最为强烈；模型组及假手术组大鼠中脑5-HT2A受体mRNA受体表达的水平明显低于对照组和手术组（P〈0．05）。结论杏仁核毁损可改善MAP大鼠的刻板行为，这可能是通过中脑5-HT2A受体mRNA表达的增高而起作用。     

中隔核毁损对甲基苯丙胺大鼠颞叶皮质多巴胺受体的影响

目的　探讨立体定向中隔核毁损对甲基苯丙胺 (MAP)大鼠脑颞叶皮质多巴胺D2 受体表达的影响。方法　 4 0只SD大鼠随机分为对照组、MAP组、MAP +毁损组和MAP +假毁损组 ,每组各 10只 ;采用经腹腔注射MAP制备精神分裂症MAP模型 ,立体定向 射频毁损中隔核 ,免疫组织化学ABC法观察颞叶皮质D2 受体的表达。结果　与对照组比较 ,MAP组及MAP +假毁损组大鼠颞叶皮质D2 受体表达有非常显著性差异 (P <0 .0 1) ;MAP+毁损组大鼠颞叶皮质DA受体阳性细胞数目与对照组比较差异无显著性 (P >0 .0 5 )。结论　中隔核毁损可以抑制使用MAP而诱发的颞叶皮质D2 表达的亢进。     

杏仁核毁损对甲基苯丙胺大鼠刻板行为和额叶皮质多巴胺的影响

目的　探讨立体定向杏仁核毁损对甲基苯丙胺 (methamphetamine ,MAP)大鼠刻板行为和额叶皮质多巴胺 (dopamine ,DA)含量的影响。方法　立体定向射频毁损杏仁核 ,经腹腔注射MAP观察大鼠行为学改变 ,荧光分光光度法测定额叶皮质DA含量。结果　杏仁核毁损组大鼠较假手术组大鼠刻板行为评分显著降低 ;甲基苯丙胺逆耐受持续时间显著缩短 ,潜伏期显著延长。MAP大鼠额叶皮质DA含量显著高于对照组 ;杏仁核毁损组的MAP大鼠额叶皮质DA含量显著低于假毁损组。结论　杏仁核毁损可有效地对抗使用甲基苯丙胺而出现的逆耐受现象 ,对额叶皮质DA增高有明显阻断作用     

立体定向边缘叶脑白质切开术对大鼠强迫检查行为学改变的影响

目的探讨立体定向边缘叶脑白质切开术对Quinpirole(QNP)引起大鼠强迫性检查行为的影响。方法给大鼠颈部皮下注射QNP建立强迫检查行为动物模型,采用立体定向进行大鼠边缘叶脑白质切开术,在开放场地观察大鼠返“家”频率、平均返回时间、运动总距离、参观地点、参观序列及预期比率,评价大鼠的行为学改变,并与假手术组和氯丙咪嗪处理组对比,观察手术对大鼠强迫检查行为的影响。结果术后2周大鼠返“家”频率及运动总距离与假手术组相比明显减少,平均返回时间延长,参观序列及实际/预期比率出现明显差异,而参观地点没有明显改变。氯丙咪嗪处理可以减弱大鼠过度返“家”次数,延长大鼠平均返回时间,但不影响其他强迫检查行为。结论边缘叶脑白质切开术和氯丙咪嗪处理均能明显改善QNP诱发的大鼠强迫检查行为。     

Effects of septal nucleus lesion on dopamine D2 receptor expression in the prefrontal lobe, striatum, and brainstem in a rat model of schizophrenia★

BACKGROUND: It has been demonstrated that the septal nucleus is involved in the pathogenesis of schizophrenia. Based on autopsies of schizophrenia patients, studies have shown a reduced number of septal nucleus neurons and glia. In addition, experimental rat models of schizophrenia have shown increased dopamine receptor D2 binding sites in the basal ganglia, septal nuclei, and substantia nigra. Previous studies have demonstrated that the septal nucleus modulates dopamine metabolic disorder and dopamine D2 receptor balance. OBJECTIVE: Dopamine D2 receptor expression in a rat model of schizophrenia, combined with antipsychotic drugs, was analyzed in the prefrontal lobe, striatum, and brainstem. In situ hybridization was used to observe the effects of stereotactic septal nucleus lesions on dopamine D2 receptor expression in the brains of methylamphetamine-treated rats. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed in the Laboratory of General Institute of Psychosurgery, Third Hospital of Chinese PLA from November 2005 to June 2006. MATERIALS: A total of 120 healthy, adult Sprague Dawley rats, weighing approximately 200 g, were included. Methylamphetamine (Sigma, USA) and an in situ hybridization detection kit for dopamine D2 receptor (Boster, China) were also used for this study. METHODS: All rats were randomly allocated to the following 4 groups, with 30 rats in each group: normal control, simple administration, septal nucleus lesion, and sham-operated groups. In the normal control group, rats were not administered or lesioned. In the remaining 3 groups, rats were intraperitoneally administered 10 mg/kg methylamphetamine, once per day, for 15 successive days to establish a schizophrenia model. Following successful model establishment, rats from the septal nucleus lesion group were subjected to stereotactic septal nucleus lesions. The cranial bone was exposed in rats from the sham-operated group, and the septal nucleus was not lesioned. MAIN OUTCOME MEASURES: At 7 days post-surgery, dopamine D2 receptor expression in the prefrontal lobe, striatum, and brainstem were detected by in situ hybridization. RESULTS: Dopamine D2 receptor expression in the rat prefrontal lobe, striatum, and brainstem was significantly higher in the simple administration group and sham-operated group, compared with the normal control group (P < 0.01). In the septal nucleus lesion group, dopamine D2 receptor expression was significantly less than the simple administration and sham-operated groups, (P < 0.01). There was no significant difference in dopamine D2 receptor expression between the simple administration and sham-operated groups (P > 0.05). CONCLUSION: Septal nucleus lesions reduce dopamine D2 receptor expression in the prefrontal lobe, striatum, and brainstem in a rat model of schizophrenia, indicating that the septal nucleus modulates dopamine D2 receptor expression. Key Words: septal nucleus; methylamphetamine; schizophrenia; in situ hybridization; dopamine D2 receptor