吗啡成瘾性大鼠脑内核团神经细胞[Ca 2+]i变化的研究

目的 研究吗啡成瘾对大鼠脑内与成瘾相关核团神经细胞[Ca 2 ]i的影响.方法 将50只SD大鼠随机分成吗啡成瘾组和对照组,观察成瘾后的戒断症状;应用对Ca2 敏感的探针Fluo-3与Ca2 络合后被激光激发发出荧光的特性,利用激光共聚焦显微镜观察伏核、海马、内侧额前皮质神经细胞[Ca 2 ]i变化,并用图像分析软件进行处理.结果 吗啡成瘾大鼠脑内伏核、海马及内侧额前皮质神经细胞[Ca 2 ]i和对照组比较明显增高(P<0.01).结论 长期使用吗啡可明显增高伏核、海马和内侧额前皮质神经细胞[Ca 2 ]i.     

吗啡成瘾大鼠脑内核团毁损后的行为学研究及形态学变化

目的研究脑内核团毁损对吗啡成瘾大鼠戒断症状及行为学方面的影响．以及毁损前后的脑形态学变化。方法将120只雄性SD大鼠随机分成对组、吗啡成瘾组、伏核毁损组、海马毁损组及伏核、海马假毁损组，通过旷场实验和隔离残杀实验观察大鼠目的性探究行为和攻击行为的变化．并在光镜和电镜下观察脑内伏核、海马的形态学变化。结果成瘾组和毁损组在自然戒断症状、旷场实验、隔离残杀实验方面经统计学分析，组间差异有统计学意义（P〈0．05）；成瘾大鼠伏核、海马的神经元细胞器减少、线粒体肿胀、染色质边集、核固缩甚至坏死。结论长期使用吗啡可导致脑内神经元超微结构损害：毁损伏核、海马后可改善成瘾大鼠的戒断症状．使其探索行为和攻击性行为发生变化。     

可卡因成瘾大鼠脑立体定向核团毁损术前后形态学及单胺类神经递质的变化

目的研究可卡因成瘾大鼠脑形态学的变化及在脑立体定向核团毁损术前后单胺类神经递质的变化。方法采用普通SD大鼠作为实验动物,随机分为对照组、成瘾组、成瘾大鼠毁损伏核组、成瘾大鼠毁损海马组、成瘾大鼠毁损扣带回组、成瘾大鼠毁损伏核-海马-扣带回组。成瘾大鼠每天皮下注射溶解于0.2ml蒸馏水的盐酸可卡因15mg/kg,正常对照组每天皮下注射0.2ml蒸馏水,持续90 d。毁损组分别行不同部位的毁损,3 d后处死,采用高效液相色谱仪(HPLC)脑组织匀浆法检测纹状体的单胺类递质含量,同时观察比较正常、成瘾及毁损后大鼠不同脑区在光镜及电镜下形态学的改变。结果成瘾大鼠纹状体多巴胺含量较正常对照组升高(P<0.01)。毁损前后大鼠单胺类递质无明显变化。在成瘾大鼠的伏核、海马、扣带回观察到核固缩、间质水肿、纤维断裂及坏死。结论长期使用可卡因可以造成大鼠脑组织的损害及纹状体多巴胺含量升高。立体定向核团毁损术前后脑组织单胺类神经递质变化不明显。     

吗啡依赖大鼠脑内相关脑区CREB mRNA的表达

目的　观察吗啡依赖和戒断时大鼠脑内转录因子CREBmRNA的变化。方法　采用逆转录PCR(RT PCR)方法 ,对CREBmRNA在吗啡依赖和戒断时大鼠脑内与阿片类物质依赖有关的前额叶皮质、海马、伏隔核和新纹状体等脑区的表达进行观察。结果　吗啡依赖和戒断时前额叶皮质以及吗啡戒断时新纹状体CREBmRNA的光密度值高于对照组 ,海马、伏隔核等处无改变。结论　吗啡依赖和戒断时CREBmRNA在某些脑区的表达升高 ,提示CREB可能与阿片类物质依赖的形成有关。     

慢性吗啡处理大鼠相关脑区脑源性神经生长因子、Bcl-2的表达

中脑腹侧被盖区和蓝斑核分别是阿片成瘾心理依赖和躯体依赖密切相关的脑区。目前尚无系统的吗啡成瘾后与阿片类依赖密切相关的脑区内脑源性神经生长因子、Bcl-2基因和蛋白水平变化的研究。实验采用免疫组化技术和原位杂交技术观察到吗啡依赖形成及戒断过程中,大鼠蓝斑、海马、前额叶皮质处的脑源性神经生长因子显著增加,Bcl-2显著降低;而腹侧被盖区,伏隔核脑区脑源性神经生长因子变化不明显,Bcl-2的表达在伏隔核脑区显著增加。提示脑源性神经生长因子和Bcl-2参与了吗啡依赖和戒断的形成。     

神经节苷脂GM1对大鼠脑液压伤后行为和记忆的影响

目的:探讨大鼠脑液压伤后GM1与学习记忆、脑内一氧化氮、突触素和细胞凋亡的关系.方法:液压损伤法建立大鼠脑损伤模型,随机分为治疗组、损伤组和对照组.观察伤后学习记忆改变,检测一氧化氮合酶(NOS)、一氧化氮(NO)、突触素和海马、皮质及基底节区细胞凋亡指数.结果:治疗组学习记忆成绩高于损伤组,NOS、NO明显降低,治疗组海马CA1区突触素显著增多,皮质、海马和基底节的凋亡细胞数明显减少.结论:GM1能减少海马和皮质细胞凋亡,可能有利于促进脑损伤后神经行为和记忆的恢复.     

用激光扫描共聚焦显微镜观察吗啡成瘾对大鼠海马神经细胞内钙离子的影响

目的　为了取得吗啡成瘾对神经细胞内钙离子 ([Ca2 ]i)影响的直接证据 ,探索吗啡成瘾的神经生物学机制及对吗啡成瘾可能的治疗途径。方法　根据新型荧光探针Fluo 3能与活细胞内 [Ca2 ]i特异性结合后发出荧光的特性 ,将 1 9只新生SD大鼠随机分成吗啡成瘾组和对照组 ,给吗啡成瘾组动物腹腔注射吗啡使其成瘾 ,用Fluo 3荧光探针对两组动物的海马神经细胞分别进行染色 ,利用激光共聚焦显微镜 (laserscanningconfocalmicroscope ,LSCM)技术对两组大鼠的海马神经细胞 (主要是锥体细胞 )内 [Ca2 ]i的变化进行了观察研究 ,并用图像分析技术进行处理。结果　吗啡成瘾大鼠海马锥体神经细胞内Ca2 浓度的平均荧光像素是对照组的 3 7倍。结论　吗啡成瘾可能明显增高大鼠海马锥体神经细胞内Ca2 浓度。     

神经节苷脂GMl对大鼠脑液压伤后行为和记忆的影响

目的探讨大鼠脑液压伤后GM1与学习记忆、脑内一氧化氮、突触素和细胞凋亡的关系.方法液压损伤法建立大鼠脑损伤模型,随机分为治疗组、损伤组和对照组.观察伤后学习记忆改变,检测一氧化氮合酶(NOS)、一氧化氮(NO)、突触素和海马、皮质及基底节区细胞凋亡指数.结果治疗组学习记忆成绩高于损伤组,NOS、NO明显降低,治疗组海马CA1区突触素显著增多,皮质、海马和基底节的凋亡细胞数明显减少.结论GM1能减少海马和皮质细胞凋亡,可能有利于促进脑损伤后神经行为和记忆的恢复.     

伏核脑深部刺激对吗啡成瘾心理依赖大鼠的作用研究

目的研究伏核脑深部刺激（DBS）对吗啡成瘾大鼠心理依赖的作用。方法将60只SD大鼠随机等分为三组：假刺激（ShS）组、DBS组、正常对照（NS）组。刺激前后行条件性位置偏爱实验，并观察伏核、海马、前额叶脑组织的形态学变化。结果刺激前DBS组与ShS组大鼠在伴药箱平均停留时间均长于NS组，差异显著（P〈0．01）；刺激后，DBS组较ShS组在伴药箱平均停留时间明显缩短（P〈0．01），而与NS组差异无统计学意义（P〉0．05）。刺激前，DBS组与ShS组大鼠伏核、海马神经元部分丢失，且水肿明显，细胞器减少；刺激后，DBS组较ShS组细胞水肿明显减轻，以伏核变化明显。结论伏核DBS有效治疗了大鼠的吗啡成瘾心理依赖作用。     

皮质发育障碍大鼠小脑回形态学和海马苔藓纤维发芽的研究

目的 探讨液氮损伤诱导局灶性皮质发育障碍大鼠海马形态学及苔藓纤维发芽的情况。方法 实验随机分为正常对照组、假手术组和液氮损伤组，建立局灶性皮质发育障碍动物模型，察看其行为改变；采用常规HE染色、Nissl染色和Timm’s硫化银组织化学方法染色，肉眼和光镜下观察大鼠脑皮质形态变化，光镜下评估海马苔藓纤维发芽情况，各组数据取苔藓纤维发芽评分，采用非参数秩和Kruskal—Wallis H检验，组间两两比较用Nemenyi法。结果 液氮损伤组大鼠行为轻微改变，鼠脑嘴尾方向形成了一小的脑回，同侧海马CA3区有苔藓纤维发芽．而正常对照组和假手术组却没有。结论 幼鼠早期液氮损伤可导致小脑回形成及海马CA3区苔藓纤维发芽。小脑回周围异常兴奋性突触环路和海马CA3区苔藓纤维发芽形成推测是局灶性皮质发育障碍导致癫痫发生的重要机制。     

咖啡因对慢性低O2高CO2大鼠学习记忆及N-甲基-D-天冬氨酸受体亚基1 mRNA表达的影响

目的：探讨咖啡因对慢性低O2高CO2处理的大鼠空间学习记忆、皮质和海马N-甲基-D-天冬氨酸受体（NMDAR）亚基1mRNA（NR1 mRNA）表达的影响。方法：SD大鼠48只分为4组,正常对照组;低O2高CO24周（HH）组,处理组：低O2高CO2＋咖啡因0．1mg·mL^-14周（HCl组）,低O2高CO2＋咖啡因0．3mg·mL^-14周（HC2组）。处理组以咖啡因水溶液干预4周后行Morris水迷宫实验,观察大鼠寻找站台的平均逃避潜伏期和游泳总距离;采用原位杂交法观察大鼠海马及皮质区NRImRNA的表达与分布情况。结果：①Morris水迷宫实验显示,HH组与对照组相比大鼠寻找站台的平均逃避潜伏期延长、游泳总距离增加（P〈0．05）,HC2组有显著性降低（P〈0．05）;②原位杂交显示NR1 mRNA阳性细胞广泛分布于海马和皮质区;模型组与对照组比较大鼠海马锥体细胞层NR1 mRNA表达的平均吸光度值降低（P〈0．05）,而咖啡因处理组平均吸光度值升高。结论：咖啡因可改善慢性低O2高CO2大鼠的空间学习记忆能力并增加海马和皮质区NR1 mRNA的表达。     

Brief social isolation in early adolescence affects reversal learning and forebrain BDNF expression in adult rats

Isolation rearing produces significant behavioral and neurochemical dysregulations in rodents. However, few studies have examined the effects of short-term isolation rearing during puberty compared to chronic social isolation from weaning to adulthood. In this study, we subjected weaning rats to a brief two-week social isolation and then re-socialized them until adulthood. We found that early isolation rearing affected reversal learning without interfering with spatial learning in the Morris water maze. We also found that brain-derived neurotrophic factor (BDNF) protein expression was increased in the medial prefrontal cortex (mPFC) but was decreased in the nucleus accumbens (NAc), CA1 and dentate gyrus of the hippocampus in isolation-reared rats. Together, our findings support the use of adolescent social isolation as a rodent model to study brain and behavior abnormalities induced by early environmental interruptions.     

A single early-life seizure impairs short-term memory but does not alter spatial learning,recognition memory,or anxiety

The impact of a single seizure on cognition remains controversial. We hypothesized that a single early-life seizure (sELS) on rat Postnatal Day (P) 7 would alter only hippocampus-dependent learning and memory in mature (P60) rats. The Morris water maze, the novel object and novel place recognition tasks, and contextual fear conditioning were used to assess learning and memory associated with hippocampus/prefrontal cortex, perirhinal/hippocampal cortex, and amygdala function, respectively. The elevated plus maze and open-field test were used to assess anxiety associated with the septum. We report that sELS impaired hippocampus-dependent short-term memory, but not spatial learning or recall. sELS did not disrupt performance in the novel object and novel place recognition tasks. Contextual fear conditioning performance suggested intact amydgala function. sELS did not change anxiety levels as measured by the elevated plus maze or open-field test. Our data suggest that the long-term cognitive impact of sELS is limited largely to the hippocampus/prefrontal cortex.     

A single early-life seizure impairs short-term memory but does not alter spatial learning, recognition memory, or anxiety

The impact of a single seizure on cognition remains controversial. We hypothesized that a single early-life seizure (sELS) on rat Postnatal Day (P) 7 would alter only hippocampus-dependent learning and memory in mature (P60) rats. The Morris water maze, the novel object and novel place recognition tasks, and contextual fear conditioning were used to assess learning and memory associated with hippocampus/prefrontal cortex, perirhinal/hippocampal cortex, and amygdala function, respectively. The elevated plus maze and open-field test were used to assess anxiety associated with the septum. We report that sELS impaired hippocampus-dependent short-term memory, but not spatial learning or recall. sELS did not disrupt performance in the novel object and novel place recognition tasks. Contextual fear conditioning performance suggested intact amydgala function. sELS did not change anxiety levels as measured by the elevated plus maze or open-field test. Our data suggest that the long-term cognitive impact of sELS is limited largely to the hippocampus/prefrontal cortex.     

Do forebrain structures compete for behavioral expression? Evidence from amphetamine-induced behavior, microdialysis, and caudate-accumbens lesions in medial frontal cortex damaged rats.

The neurochemical basis of behavioral changes following medial frontal cortex damage were investigated. Experiment 1 examined locomotion in response to D-amphetamine (1.5 and 5 mg/kg) in rats that had received bilateral aspirative lesions of the medial frontal cortex alone or in combination with 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens or caudate-putamen. Relative to controls, medial frontal cortex rats were initially hypoactive (day 1 postoperative) but rapidly became hyperactive (days 5-15 postoperative). Locomotor-time profiles and stereotypy ratings showed that amphetamine produced a selective enhancement of locomotion at the expense of stereotyped behavior. Nucleus accumbens lesions blocked the locomotion but enhanced stereotyped behavior in the medial frontal cortex damaged rats, suggesting that amphetamine-enhanced locomotion is dependent upon the integrity of the nucleus accumbens. In Experiment 2, intracerebral microdialysis was used to examine whether alterations in dopamine (DA) or monoamine metabolites in the nucleus accumbens or caudate-putamen accompanied the lesion-induced changes in locomotion. There were no differences in extracellular DA or monoamine levels between control rats and medial frontal cortex rats when tested on day 1 or day 15 postsurgery, either when they were at rest, while they walked on a motor-driven belt, or after amphetamine treatment. Therefore, it seems unlikely that changes in amphetamine-induced locomotion following medial frontal cortex lesions are related to underlying modifications in dopaminergic activity in the nucleus accumbens. It is suggested that neural structures compete for behavioral expression and that postlesion behavioral alterations reveal the competitive advantage of remaining intact neural systems.     

去松果体对大鼠学习能力及大脑皮质NOS表达的影响

目的探讨去松果体后其功能减退致褪黑素（ＭＴ）分泌减少对大鼠学习能力及大脑皮质一氧化氮合酶（ＮＯＳ）表达的影响。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二组,实验组手术摘除松果体,对照组给予假手术,饲养４０天后再行Ｙ型迷宫测试,ＳＡＢＣ法检测神经元型一氧化氮合酶（ｎＮＯＳ）表达。结果实验组大鼠学习能力明显低于对照组大鼠（Ｐ〈０．０１）,而大脑皮质、内侧隔核－斜角带核（Ｓ     

Behavior alters the uptake of [3h]choline into acetylcholinergic neurons of the nucleus basalis magnocellularis and medial septal area

Behavioral experience changed sodium-dependent high affinity choline uptake (SDHACU) in the hippocampus and frontal cortex. Rats were trained on various behavioral tasks and sacrificed after testing. SDHACU was determined in frontal cortex and hippocampus, areas that receive cholinergic innervation from the nucleus basalis magnocellularis (NBM) and the medial septal area (MSA), respectively. Untrained rats taken directly from their home cages had fairly consistent levels of SDHACU in the hippocampus (1.76 ± 0.45, X ± S.E.) and frontal cortex (1.46 ± 0.37). In the hippocampus of rats performing in a radial maze and T-maze and in rats that surpassed a criterion level in an active avoidance task, SDHACU increased significantly above Cage (untrained) group levels. In the cortex of rats performing the radial maze task, SDHACU decreased slightly. There were no other changes in frontal cortical SDHACU. After behavioral testing ceased, SDHACU in rats performing the radial maze task remained elevated above Control and Treadmill group levels for 20 days, but returned to near control levels 40 days later. Our data demonstrate that a functional differentiation exists between the MSA and NBM cholinergic systems, and that the measurement of SDHACU in central cholinergic neurons is a useful tool to identify the influences of behavior and environment upon changes in neurochemical events and neuronal activity.     

吡格列酮对糖尿病大鼠中枢神经系统PPAR-γ表达的影响

目的 研究吡格列酮对糖尿病大鼠海马、下丘脑处PPAR-γ表达的影响及与大鼠认知功能的关系.方法 雄性SD大鼠随机分为对照组(C组)、糖尿病组(D组)、糖尿病+吡格列酮组(DP组),每组10只.8周后行Morris水迷宫评价大鼠的空间学习记忆能力,Western Blot方法检测大鼠海马、下丘脑处PPAR-γ表达水平.结果 Morris水迷宫中,D组大鼠逃避潜伏期较C组和DP组延长差异均有统计学意义(P<0.05).大鼠海马和下丘脑处,PPAR-γ的表达D组较C组减少,DP组较D组增多,差异均有统计学意义(P<0.05).结论 吡格列酮能够增加糖尿病大鼠海马、下丘脑组织局部PPAR-γ表达水平,并且这种表达的增加可能是吡格列酮改善糖尿病大鼠空间学习记忆能力的机制之一.