柴胡总皂甙对戊四氮慢性点燃大鼠痫性发作及脑电图的影响

目的 评价柴胡有效成分中柴胡总皂甙对戊四氮（PTZ）慢性点燃大鼠痫性发作及脑电图的影响。方法 将48只健康SD大鼠随机等分为6组,即空白组、生理盐水组、丙戊酸钠（VPA）组和柴胡总皂甙高、中、低3种剂量组,除空白组不做处理外．其他组采用腹腔注射PTZ进行慢性点燃造模,造模同时给予以上不同处理因素,连续4周．在此期间记录大鼠痫性发作级别及次数,最后描记大鼠脑电图。结果 柴胡总皂甙高、中、低3个剂量组在实验2周时可以降低大鼠的痫性发作率,其中以高剂量组显著（P〈0．05）,柴胡皂甙高剂量组应用4周时能明显降低PTZ慢性点燃大鼠的点燃率（P〈0．05）,并明显降低痫性发作级别（P〈0．01）;各组间脑电图也存在一定差异。结论 柴胡总皂甙可拮抗PTZ慢性点燃大鼠的痫性发作．并有一定的对抗PTZ慢性点燃作用。     

戊四氮点燃模型大鼠海马苔藓纤维出芽与Cdk5/p35表达的动态变化

目的：动态观察细胞周期素依赖性激酶5（cyclin-dependent kinase5，Cdk5）和调节亚基p35在戊四氮（pentylenetetrazole，PTZ）致痫大鼠海马各区的表达变化，及其与苔藓纤维出芽（mossy fiber sprouting，MFS）的关系，以探讨其在癫痫发病机制中的作用。方法：SD雄性成年大鼠120只，随机分为PTZ组和对照组；PTZ组分为PTZ第1次注射后3d、1周、2周、4周、6周共5个亚组，每亚组12只，对照组随机分为5个亚组，与眦组各时间点对应。以上各亚组再分2个小组，每小组6只大鼠，分别进行（1）免疫组织化学和原位杂交，检测各时间点Cdk5与p35蛋白和mRNA在海马CA1和CA3区、齿状回颗粒细胞层和门区的表达；（2）Timm染色并评分。结果：PTZ组大鼠上述各区Cdk5和p35mRNA在第3天时表达即有明显上调（P＜0．01），第4周仍维持在较高水平，第6周时基本恢复到对照组水平；各区Cdk5和p35蛋白表达从第3天起即上调（P＜0．01），第2周时最强，其后下调，至第6周接近或达到对照组水平。PTZ组CA3区在点燃前MFS评分1～4分，点燃后MFS评分4～5分。MFS的变化趋势与Cdk5和p35的表达一致。结论：海马Cdk5／p35的表达变化可能参与苔藓纤维出芽，从而促进癫痫的发生。     

佐匹克隆对大鼠化学点燃效应的影响

①目的　探讨佐匹克隆 (zpl)对大鼠戊四唑 (PTZ)化学点燃和对小鼠氨基脲惊厥的影响。 ②方法制备大鼠PTZ化学点燃模型 ,对已点燃大鼠分别给予zpl 1 .5、3.0、5 .0mg/kg灌胃 ,30min后PTZ 35mg/kg腹腔注射 ,观察大鼠行为发作情况 ,大鼠行为发作按Ono标准分级 ,计算 6级发作百分率并与用药前比较 ;小鼠zpl(0 .5、1 .5、3.0mg/kg)灌胃给药 30min后 ,氨基脲 (1 5 0mg/kg)尾静脉注射 ,观察小鼠行为活动变化 ,记录小鼠阵挛惊厥的潜伏期及存活时间。③结果　zpl 3.0、5 .0mg/kg可降低点燃大鼠行为发作强度 ,与用药前比较其Ono分级和 6级发作的百分率均有显著性差异 (t =2 .1 9,P <0 .0 5 ,t =5 .2 6 ,P <0 .0 1 ;χ2 =4 .6 8,P <0 .0 5 ,χ2 =1 0 .74 ,P <0 .0 1 ) ;zpl 1 .5、3.0mg/kg灌胃用药延长了小鼠氨基脲惊厥的潜伏期及存活时间 ,与对照组比较有显著性差异 (t =2 .2 0～ 3.81 ,P <0 .0 5、0 .0 1 )。④结论　zpl对大鼠PTZ化学点燃和小鼠氨基脲惊厥均有明显的抑制作用     

氯胺酮在利多卡因化学性点燃大鼠的量效关系

目的观察氯胺酮对大鼠化学性点燃模型的作用,并了解其是否有量效关系。方法建立利多卡因化学性点燃模型大鼠,观察氯胺酮对利多卡因点燃的影响。结果氯胺酮20.0~30.0 mg.kg-1,ip可降低利多卡因化学点燃模型大鼠降低Rac ine's发作级别(P<0.05),并降低V级发作率。结论氯胺酮能抑制大鼠利多卡因化学性点燃发作,并有显著的量效关系。     

The social cognitive neuroscience of aggression,violence, and psychopathy

Social status is a key regulator of health and reproduction in mammals, including humans. Despite this, relatively little is known about how social status influences the mammalian brain. Furthermore, the extent to which status is an independent construct, i.e., not simply acting as a psychosocial stressor, is yet to be determined. Research to date reveals several promising mechanisms and/or systems associated with social status, including monoamine systems, hypothalamic neuroendocrine axes, and the hippocampus, though whether these differences are the cause or effect of status is often unclear. We review these candidates and propose how best to approach this research question in the future.     

Amygdala hypersensitivity in response to emotional faces in Tourette's patients

Abstract

Objectives. Tourette's syndrome is characterised by motor and vocal tics as well as a high level of impulsivity and emotional dysregulation. Neuroimaging studies point to structural changes of the basal ganglia, prefrontal cortex and parts of the limbic system. However, there is no link between behavioural symptoms and the structural changes in the amygdala. One aspect of daily social interaction is the perception of emotional facial expressions, closely linked to amgydala function. Methods. We therefore investigated via fMRI the implicit discrimination of six emotional facial expressions in 19 adult Tourette's patients. Results. In comparison to healthy control group, Tourette's patients showed significantly higher amygdala activation, especially pronounced for fearful, angry and neutral expressions. The BOLD-activity of the left amygdala correlated negatively with the personality trait extraversion. Conclusions. We will discuss these findings as a result of either deficient frontal inhibition due to structural changes or a desynchronization in the interaction of the cortico-striato-thalamo-cortical network within structures of the limbic system. Our data show an altered pattern of implicit emotion discrimination and emphasize the need to consider motor and non-motor symptoms in Tourette's syndrome in the choice of both behavioural and pharmacological treatment.     

SB‐334867, an orexin receptor 1 antagonist,decreased seizure and anxiety in pentylenetetrazol‐kindled rats

Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system (CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin‐A and orexin‐B are brain neuropeptides originating from postero‐lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, this study was designed to evaluate the effect of OX1 receptor antagonist (SB‐334867) on seizure‐ and anxiety‐related behaviors of pentylenetetrazol (PTZ)‐kindled rats. Kindling was induced by repeated intraperitoneal (IP) injections of PTZ (32 mg/kg) with two‐day intervals for 24 days in male Wistar rats. Three groups received intracerebroventricular (ICV) injections of SB‐334867 (2.5, 5, and 10 μg/rat) before PTZ injections. Two control groups received vehicle (2 μL/rat, ICV) and valproate (26 μg/rat, ICV) before PTZ injections. An extra group of control animals received saline both ICV and IP. Seizure‐related behaviors were monitored for 30 min following PTZ administration. The anxiety‐like behaviors were also assessed using elevated plus‐maze in the first and last days of the study. The results revealed that ICV injection of SB‐334867, mainly at the dose of 10 μg/rat, decreased the median of seizure stages, prolonged the latency and reduced the duration of different seizure stages, and reversed the PTZ‐induced anxiety‐like behaviors. Based on the presented results, it is suggested that pharmacological blockade of the OX1 receptor is a potential target in the treatment of seizure and concomitant anxiety disorders.     

Gaining insight into adolescent vulnerability for social anxiety from developmental cognitive neuroscience

Social anxiety disorder (SAD) markedly impairs daily functioning. For adolescents, SAD can constrain typical development precisely when social experiences broaden, peers’ opinions are highly salient, and social approval is actively sought. Individuals with extreme, impairing social anxiety fear evaluation from others, avoid social interactions, and interpret ambiguous social cues as threatening. Yet some degree of social anxiety can be normative and non-impairing. Furthermore, a temperament of behavioral inhibition increases risk for SAD for some, but not all adolescents with this temperament. One fruitful approach taken to understand the mechanisms of social anxiety has been to use neuroimaging to link affect and cognition with neural networks implicated in the neurodevelopmental social reorientation of adolescence. Although initial neuroimaging studies of adolescent SAD and risk for SAD underscored the role of fear-processing circuits (e.g., the amygdala and ventral prefrontal cortex), recent work has expanded these circuits to include reward-processing structures in the basal ganglia. A growing focus on reward-related neural circuitry holds promise for innovative translational research needed to differentiate impairing from normative social anxiety and for novel ways to treat adolescent SAD that focus on both social avoidance and social approach.