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。     

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     

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。     

大鼠脑中隔核毁损对关联性条件化恐惧的影响

目的：中隔核(Septum)在实验大鼠对关联性刺激所产生的条件化恐惧的获得(Acquisi-tion)已经证明具有重要的作用，但对关联性刺激所产生的条件化恐惧的表达(Expression)的作用至今仍未阐明。方法：实验组大鼠分别采用射频(Radiofrequency)技术对双侧中隔核区行组织毁损术，对照组大鼠完全按照实验组大鼠的手术程序，但不采用射频技术进行组织破坏，然后均接受经典的条件化恐惧的实验训练。实验1：实验大鼠(n=18)在手术后第11d，经采用足部电击(Footshocks)方法产生与之关联的条件化恐惧，然后在24h后，在相同条件下但不予以足部电击的情况下评定其僵滞(Freezing)行为；实验2：实验大鼠(n=16)在手术前24h，先采用足部电击方法产生与之关联的条件化恐惧，然后在手术后第11d在相同条件下但不予以足部电击的情况下评定僵滞行为。结果:在训练前接受双侧中隔核毁损的大鼠既不阻断也不增强关联性条件化僵滞，而在训练后接受双侧中隔核毁损的大鼠则明显阻断关联性条件化僵滞的表达，同时因关联性条件化恐惧所致非粪的数量也明显减少。结论:双侧中隔核的毁损并不引起关联性条件化恐惧的增强，而是明显减弱关联性条件化恐惧的表达水平，因此，中隔核具有潜在增强关联性条件化恐惧的表达的作用。     

海洛因成瘾大鼠伏隔核毁损术前后觅药行为及多巴胺神经递质的变化

目的研究海洛因成瘾大鼠毁损伏隔核前后觅药行为及多巴胺神经递质的变化。方法建立海洛因成瘾大鼠模型，毁损大鼠双侧伏隔核，利用条件性位置偏好实验测定成瘾前、后，术前、术后成瘾大鼠觅药行为的变化，利用高效液相方法测定边缘系统多巴胺神经递质的变化。结果毁损大鼠双侧伏隔核能够完全消除条件性地点偏好。成瘾大鼠边缘系统多巴胺含量较对照组明显增高。毁损前后大鼠边缘系统多巴胺含量无明显变化。结论伏隔核是调节强化作用的重要位置，长期使用海洛因可使大鼠边缘系统多巴胺含量明显增高，但毁损前后无明显变化，与条件性位置偏好表现不同步。     

伏核毁损对精神分裂症模型大鼠行为和学习记忆能力的影响

目的　探讨毁损伏核对调控精神分裂症行为的有效作用及对学习记忆能力的影响 ,为精神分裂症外科治疗提供参考。方法　给大鼠腹腔内注射苯环己哌啶 (PCP)制作精神分裂症动物模型。采用立体定位仪 ,电极毁损大鼠伏核 ,观察社会行为、刻板行为评分 ,并进行Morris水迷宫实验。结果　毁损伏核组能使精神分裂症模型大鼠刻板行为和运动失调有所减轻 ,与假毁损组比较差异具有显著性 (P <0 .0 5 )。水迷宫实验毁损组在初期空间记忆能力的建立上存在缺陷 ,与假毁损组比较差异具有显著性 (P <0 .0 5 )。结论　伏核毁损能改善精神分裂症症状 ,对大鼠初期学习记忆能力有一定影响     

杏仁核亚核群毁损对PCP模型大鼠行为和递质的影响

目的探讨杏仁核亚核群毁损后五氯苯酚(pentachlorophenol,PCP)模型大鼠行为和前额叶单胺类递质含量的变化,为立体定向技术治疗精神病提供参考。方法经腹腔注射PCP制作精神分裂症动物模型,立体定向电极毁损大鼠杏仁核,对其刻板行为进行评分,应用高效液相色谱分析系统检测前额叶多巴胺(DA)、5-羟色胺(5-HT)和去甲肾上腺素(NE)的含量。结果杏仁核内侧核群毁损能减轻PCP模型大鼠的刻板行为和社会行为,与假毁损组之间具有非常显著性差别(P<0.001)。毁损组前额叶DA含量低于假毁损组(P <0.05),5-HT和NE含量均高于假毁损组(P<0.05)。结论PCP模型大鼠前额叶DA含量增高,5-HT和NE含量下降。立体定向毁损杏仁核内侧核群能够改变前额叶单胺类递质的水平,改善模型大鼠精神分裂症症状。     

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。     

新靶点前连合隔核隔区毁损治疗难治性癫痫

作者应用脑立体定向术毁损前连合、隔核、隔核前区新靶点治疗难治性癫痫12例,术后癫痫消失8例,大发作转为小发作4例,服药量减少50％,无手术死亡和严重并发症。     

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。     

Characteristics of memory impairment following lesioning of the basal forebrain and medial septal nucleus in rats

Memory impairment in rats with lesions of the basal forebrain (BF) and medial septal nucleus (MS) including cell bodies of the cortical and septohippocampal cholinergic systems, respectively, were compared in order to evaluate the functional contribution of the two cholinergic systems to memory. Biochemical assay revealed that lesioning of the BF and MS resulted in marked and selective decreases in both choline acetyltransferase and acetylcholinesterase activities in the cerebral cortex and hippocampus, respectively. Rats with BF lesions exhibited a severe deficit in a passive avoidance task; acquisition of passive avoidance by repeated training was sluggish, and the acquired response was rapidly eliminated in a subsequent extinction test. However, only slight impairment of passive avoidance was observed in rats with MS lesions. Memory impairment in rats with BF or MS lesions was also investigated using two spatial localization tasks, the Morris water task and the 8-arm radial maze task. Both BF and MS lesions elicited a significant impairment in the Morris water task that required reference memory, as demonstrated by an apparent increase in the latency to escape onto a hidden platform in a large water tank. The impairment was much more obvious in the BF-lesioned rats. In contrast, in the radial maze task primarily requiring working memory, rats with lesions of the MS showed severe disruption, exhibiting a marked increase in total errors, a decrease in the number of initial correct responses, and an apparent change in the strategy pattern. However, corresponding changes in the rats with BF lesions were slight. These results suggest that BF lesions may lead to substantial long-term memory impairment while MS lesions may primarily produce short-term or working memory impairment, indicating a qualitatively different contribution of the two cholinergic systems to memory. It is also suggested that these two experimental animal models may be useful for evaluation of therapeutic drugs for senile dementia of the Alzheimer type.     

Effects of inhibiting neonatal methamphetamine-induced corticosterone release in rats by adrenal autotransplantation on later learning,memory, and plasma corticosterone levels

Rationale

Neonatal rat methamphetamine (MA) exposure has been shown to cause long-term behavioral impairments similar to some of those observed following neonatal stress. The mechanism by which MA induces impairments is unknown but may be related to early increases in corticosterone release. We previously developed a method to attenuate MA-induced corticosterone release using adrenal autotransplantation (ADXA) in neonatal rats. This exposure period corresponds to the second-half of human pregnancy.

Objective

To determine whether inhibition of neonatal MA-induced increases in corticosterone attenuates the long-term behavioral deficits associated with early MA treatment.

Results

ADXA successfully attenuated MA-induced plasma corticosterone increases by ∼50% during treatment (P11–20) but did not attenuate the long-term behavioral effects of MA treatment. MA-treated rats, regardless of surgery, showed increased errors and latencies in the Cincinnati water maze test of egocentric learning and increased latency, path length, and cumulative distance in three phases of Morris water maze spatial learning and reference memory. MA-treated offspring were hypoactive, had subtle reductions in anxiety in the elevated zero maze but not in the light-dark test. ADXA had no effect on MA-induced long-term 5-HT reductions in the neostriatum or entorhinal cortex or on 5-HIAA reductions in the hippocampus.

Conclusions

Fifty percent attenuation of neonatal MA-induced elevations in corticosterone does not alter the long-term egocentric or allocentric learning deficits or other behavioral effects of neonatal MA exposure. Because the ADXA effect was partial, the data cannot rule out the possibility that a more complete block of MA-induced corticosterone release might not prevent later cognitive deficits.     

Cross-species embryonic septal transplants: restoration of conditioned learning behavior

Embryonic septal and hippocampal tissue from mice was transplanted between species into the brains of adult rat hosts as cell suspensions. Deficits in the ability to learn a conditioned, hippocampally mediated, forced alternation behavior, which were caused by a bilateral transection of the fornix-fimbria pathway, were ameliorated in the septal transplant recipients. The successful performance of the task was correlated to the density index of acetylcholinesterase in the hippocampal section.     

去松果树对大鼠学习记忆及大脑皮质胆碱能纤维的影响

目的　探讨松果体功能减退致褪黑素 (MT)分泌减少对大鼠学习记忆及大脑皮质胆碱能纤维分布的影响。方法　将大鼠进行Y型迷宫测试 ,淘汰学习障碍的大鼠 ,将学习正常的大鼠随机分 2组 ,实验组手术摘除松果体 ,对照组给予假手术 ,饲养 40d后再行Y型迷宫测试 ,乙酰胆碱酯酶 (AChE)组织化学法测AChE。结果　实验组大鼠学习成绩由术前 (14.7± 5 .0 )次增加到术后(2 8.7± 2 .4)次 ,学习记忆能力明显低于术前自身及对照组 (13.8± 8.3)次 (P <0 .0 1) ,运动皮质、体感皮质第Ⅱ～Ⅳ层 ,海马CA1、CA2、CA3区辐状层、腔隙层、分子层和齿状回多形细胞层AChE阳性纤维密度明显低于对照组 (P <0 .0 1)。结论　大鼠松果体摘除可以引起大鼠学习记忆障碍及大脑皮质胆碱能纤维密度降低     

Comparison of medial and lateral septal neuron activity during performance of spatial tasks in rats

The septal complex, having close and reciprocal connections with the hippocampus, is known to play an important role in learning and memory. Anatomically, the septal complex is divided into the medial and lateral areas (MS and LS). In the present study, in order to elucidate functional differences between the MS and LS, we recorded single unit activity in the MS or LS and electroencephalogram (EEG) in the hippocampus simultaneously while the rats performed the following 2 spatial tasks in an open‐field chamber. In task 1, the rat received rewarding intracranial electrical stimulation (ICES) when it entered in a reward place that was set randomly in the open field in each trial. In task 2, the rat received rewarding ICES when it alternately visited two fixed reward places in the open field. Unit activity was analyzed in relation to the pattern of hippocampal EEG, and rat's location, locomotion direction and locomotion speed in the spatial tasks. A total of 47 neurons were recorded in the septal complex (MS, 19; LS, 28). The majority of neurons with activity correlated with hippocampal EEG were found in the MS (14/19). All of the neurons with place‐related activity (an increase in unit activity when the rat was in a specific location in the open field) were found in the LS (n = 15). The majority of neurons with direction‐related activity were found in the LS (18/23). Twenty‐one neurons displayed speed‐related activity (MS, 9; LS, 12). The present results indicate that (1) the MS is directly involved in the formation and control of hippocampal EEG patterns, and (2) the LS is important for the processing and integration of spatial information in the environment. Hippocampus 1999; 9:220–234. © 1999 Wiley‐Liss, Inc.     

神经干细胞移植对阿尔茨海默病大鼠海马突触素表达和学习记忆能力的影响*

背景：前期实验已证实,移植入阿尔茨海默病大鼠脑内的神经干细胞能够存活、增殖,但其是否可替代损伤或坏死的神经细胞而重建神经通路,改善学习记忆能力尚不清楚。突触素是突触重建的重要标记之一。 目的：观察神经干细胞移植对阿尔茨海默病大鼠学习记忆能力及突触表达的影响。 方法：SD大鼠随机数字表法分为正常对照组、阿尔茨海默病模型组、2周移植组和4周移植组,除正常对照组外制备阿尔茨海默病模型。另取新生24 h SD大鼠海马齿状回分离、培养神经干细胞,经Hoechst33258标记后植入2周和4周移植组海马CA1区,行Y迷宫实验检测大鼠的学习记忆能力,然后取脑进行尼氏染色和突触素免疫组织化学染色。阿尔茨海默病模型组则以同样的方法、同样的位点注入等量无菌生理盐水。正常对照组不施以任何处理。 结果与结论：①2周和4周移植组海马CA1区细胞比阿尔茨海默病模型组增多,但仍少于正常对照组(P < 0.05),平均吸光度与正常对照组相比差异无显著性意义(P > 0.05)。②2周移植组和4周移植组大鼠海马结构内突触素吸光度值明显高于正常对照组和阿尔茨海默病模型组(P < 0.05)。③与阿尔茨海默病模型组相比,2周和4周移植组大鼠学习能力和记忆能力均显著增强,正确反应率明显提高(P < 0.05),而与正常对照组相比,差异无显著性意义(P > 0.05)。提示移植入脑内的神经干细胞可促进突触形成,改善学习记忆能力。     

人参皂甙Rd对颞叶癫大鼠学习记忆能力及海马5-HT表达的影响

目的研究人参皂甙Rd对氯化锂-匹罗卡品点燃颞叶癫(temporal lobe epilepsy,TLE)大鼠学习记忆能力及海马5-HT表达的干预作用。方法建立氯化锂-匹罗卡品点燃颞叶癫大鼠模型,将30只造模成功的颞叶癫大鼠随机分为TLE组(生理盐水10ml/kg腹腔注射,15只)及GSRd干预组(人参皂甙Rd2mg/kg腹腔注射,15只),另选15只大鼠作为正常对照组;采用Morris水迷宫及免疫组化染色分别检测各组大鼠学习记忆能力及海马5-HT表达水平。结果与正常对照组比较,TLE组大鼠学习记忆能力下降,海马5-HT表达明显减少(P0.05);与TLE组比较,GSRd干预组可显著提高大鼠学习记忆能力及海马5-HT的表达水平(P0.05)。结论人参皂甙Rd可能通过增加海马5-HT的表达来提高颞叶癫大鼠学习记忆能力。     

Change in cerebral glucose metabolism during limbic seizures elicited from lateral septal nucleus

The roles of the amygdala and hippocampus have been extensively studied in limbic seizures. Although the septal nuclei have a close connection to the hippocampus and affect emotional behavior, the effect on limbic seizures is still unclear. We have reported that characteristic sham-rage seizures were observed in cats, by administering a local injection of kainic acid (KA) into the lateral septal nucleus (LSN). This study investigated the electrophysiological features of KA-induced septal seizures in rats and analyzed the process in relation to the cerebral glucose metabolism using [¹⁴C]deoxyglucose autoradiography. On EEG, epileptic discharge eliciting from the LSN rapidly propagated to the hippocampus and the amygdala. Behavioral change was similar to that in limbic seizures induced by intraamygdaloid KA. Sham-rage seizure was not observed in rats. However, the local cerebral glucose metabolism during the seizures increased not only in the limbic structures including the LSN but also in the hypothalamus and periaqueductal grey matter of the midbrain. The findings were distinctive of septal seizures as compared with amygdaloid seizures. The results suggested that sham-rage seizures in cats might be caused by a secondary epileptogenic excitation in the hypothalamus or periaqueductal grey matter of the midbrain. The septal nuclei may play an important role in emotional behavior associated with limbic seizures even if there is a species difference in its function.