地佐环平马来酸盐对大鼠甲基苯丙胺辨别效应的影响(英文)

目的:研究兴奋性氨基酸NMDA受体拮抗剂地佐环平马来酸盐对甲基苯丙胺辨别行为的作用。方法:采用双杆、固定比率食物强化型辨别实验程序。结果:大鼠对甲基苯丙胺(1.0mg/kg,sc)可以产生辨别行为,并稳定地维持该行为。在用地佐环平马来酸盐(0.1mg/kg,sc)的替代实验中,1只大鼠的行为表明地佐环平马来酸盐无替代作用,其余6只均表明该剂量下地佐环平马来酸盐具有不同程度的替代甲基苯丙胺的辨别效应;但是地佐环平马来酸盐(0.025,0.05mg/kg,sc)均没有替代作用。在拮抗实验中,地佐环平马来酸盐(0.10mg/kg,sc)不同程度地拮抗甲基苯丙胺的辨别效应(P<0.01);而地佐环平马来酸盐(0.025,0.05mg/kg,sc)均没有拮抗甲基苯丙胺的辨别效应的作用。结论:NMDA受体可能与甲基苯丙胺精神依赖性有关。     

急性应激障碍向创伤后应激障碍发展小鼠模型的制备

目的 制备急性应激障碍(ASD)向创伤后应激障碍(PTSD)发展的小鼠模型,为应激障碍机制研究和防治药物评价提供动物模型.方法 雄性C57BL/6J小鼠,每日足底电击,电流0.8 mA,每次持续10 s,间隔时间10 s,重复15次,连续电击3 d,同时设正常对照组.急性期行为学实验于足底电击后第1～第3天进行;慢性期...     

创伤后应激障碍简述

2004-12底发生的印度洋海啸令全世界震惊和悲痛。随着救援工作的推进，人们关注的焦点逐渐从遇难者转向幸存者，据相关报道显示，至少800名泰国幸存者患上了后海啸恐惧症，他们担心海啸还会卷土重来；一些幸存者为同伴相继死去而自己却生存下来感到负罪，甚至想要自杀；还有许多人脑海中不时出现灾情场面，或是仿佛听到海啸警报声；     

急性应激障碍向创伤后应激障碍转化模型的建立

目的建立小鼠急性应激障碍(ASD)向创伤后应激障碍(PTSD)转化的模型。方法雄性C57BL/6J小鼠(6-8周龄)采用电击刺激(0.8 m A,每次10 s,每天15次,3 d)造模,造模后24 h和28 d后测量焦虑、回避、再体验症状。通过行为轮廓法(behavior profile),分离出在急性期和慢性期患病的小鼠。结果在电击应激后24 h,应激组小鼠表现出明显的回避行为(P=0.0012)、在电击环境中的僵直行为(P<0.01)和明显的焦虑行为(P=0.002)。在电击后28天,应激组小鼠同对照组相比仍然表现出显著的焦虑行为(P=0.0889)、回避行为(P<0.01)和在电击环境中的僵直行为(P=0.0138)。通过行为轮廓法,以对照组各项行为学数据的平均值±0.5标准差为界限,定义在三项行为学测试中,均超过或低于界限的小鼠为患病小鼠。通过筛选,在应激后24 h对照组小鼠有1只患病,模型组有15只患病,患病率分别为4%和57.69%。在应激后28 d,对照组小鼠患病2只,应激组患病8只,患病率分别为8%和30.77%,应激组小鼠的创伤后应激障碍患病率同临床数据相似。其中应激组在急性期和慢性期均患病的小鼠有6只,急性应激障碍向创伤后应激障碍的转化率为40%。结论成功建立了小鼠急性应激障碍向创伤后应激障碍转化的模型,可用于相关机制研究和药物筛选。     

组胺对地佐环平诱发的SD大鼠八臂迷宫空间记忆障碍的改善作用

AIM: To investigate whether or not histamine is involved in spatial memory deficits induced by dizocilpine (MK-801) as evaluated by 8-arm radial maze of rats. METHODS: 8-Arm (4-arm baited) radial maze was used to measure spatial memory in rats. RESULTS: Bilaterally intrahippocampal (ih) injection of MK-801 (0.3μg/site) impaired working memory and reference memory in rats. Both histamine (50, 100 ng/site, ih) and intraperitoneal(ip) injection of histidine (100, 200 mg/kg) markedly improved the spatial memory deficits induced by MK-801. On the other hand, the ameliorating effect of histidine (100 mg/kg, ip) was completely antagonized by α-fluoromethylhistidine (α-FMH, 5μg/site, ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H1-antagonist pyrilamine (1μg/site, ih), but not by H2-antagonist cimetidine, even at a high dose (2.5μg/site, ih).CONCLUSION: The hippocampal histamine plays an important role in the ameliorating effect on MK-801-induced spatial memory deficits, and its action is mediated through postsynaptic H1-receptor.     

四逆散对创伤后应激障碍所致睡眠障碍大鼠海马超微结构的影响

目的研究中药复方四逆散对创伤后应激障碍大鼠海马超微结构的影响。方法按照随机数表法将SD雄性大鼠随机分为5组,每组10只:空白对照组、模型组、阴性对照组、阳性对照组、实验组。除空白对照组外,其余4组动物均复制应激模型。模型组和空白对照组的大鼠饮食正常。于造模前1 h,阴性对照组的大鼠灌胃0.9%Na Cl;阳性对照组的大鼠灌胃盐酸帕罗西汀溶液4.2mg·kg^-1;实验组的大鼠灌胃四逆散水煎液2.41 g·kg^-1。灌胃容积10m L·kg^-1,每日灌胃1次,连续给药7 d。造模结束后,各组大鼠立即进行心脏灌注,采集海马组织,于30000倍电镜下观察并比较各组大鼠海马CA1、CA3区超微结构的差异性。结果空白对照组的海马CA1和CA3区的神经元细胞器丰富,线粒体圆形或长杆状,线粒体嵴结构清晰,粗面内质网呈条索样分布,核糖体丰富,高尔基复合体常见。模型组与空白对照组比较,细胞器明显损伤,细胞质结构空旷,线粒体肿胀,线粒体膜及嵴结构消失,粗面内质网池样扩张,提示幽闭电击对大鼠海马区神经元内细胞器产生明显损伤。阴性对照组与模型组比较,变化与其相似,提示0.9%Na Cl灌胃对大鼠没有明显的应激影响;而阳性对照组和实验组的海马区神经元细胞质内细胞器结构明显恢复,2组结构基本相似,提示盐酸帕罗西汀和四逆散均能明显改善PTSD大鼠海马区神经元细胞器结构。结论四逆散可以明显改善创伤后应激障碍大鼠海马CA1和CA3区神经元细胞器结构。     

浅谈针刺防治疫情所致创伤后应激障碍

新型冠状病毒肺炎(COVID-19)疫情暴发后,在恐惧的氛围下,许多人产生了焦虑、抑郁等紧张情绪,创伤后应激障碍(PTSD)的发病率也随之增高.针刺作为一种传统的中医疗法,对很多精神类疾病的治疗有其独特的优势.笔者通过总结和分析针刺治疗PTSD的相关研究,发现电针疗法更能有效改善PTSD患者临床症状,调节杏仁核、海马、...     

地佐环平对兔视神经损伤后视网膜神经节细胞调节作用的研究

目的探讨地佐环平（Dizoclipine,MK-801）对兔视神经损伤后视网膜神经节细胞的保护作用。方法30只健康雄性日本大耳白家兔随机分为5组,双眼制作视神经损伤模型。5组动物左眼为治疗组,于玻璃体腔内注入MK-801溶液;右眼为对照组,同法注入等量0．9％氯化钠溶液。于1、3、7、14、28d各处死1组家兔,摘取双眼进行视网膜末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）,光镜下记数对应部位存活视网膜神经节细胞数及TUNEL染色阳性细胞数。结果治疗组各时段治疗组存活视网膜神经节细胞数与对照组比较差异有统计学意义（P〈0．05）;除视神经损伤1d外,余时间点治疗组TUNEL阳性细胞数与对照组比较差异有统计学意义（P〈0．05）。结论MK-801对兔视神经损伤后视网膜神经节细胞具有一定保护作用。     

心理护理干预对青少年创伤后应激障碍的影响

目的:探讨和分析心理护理干预对青少年创伤后应激障碍的影响.方法:选取2019年1月至12月期间我院的60例创伤后应急障碍青少年患者展开研究.以随机的方法将患者分成各30例的参考组与研究组,在对患者治疗过程中分别实施常规护理和心理护理干预;对比两组患者的实际改善效果.结果:干预后研究组患者的SAS评分与SDS评分均显著低...     

术中知晓所致创伤后应激障碍的护理分析

麻醉术中知晓可能会导致手术后患者不良的心理症状.有术中知晓存在的患者,特别是由此而带来严重创伤体验的患者,往往在术后可能会发展成为创伤后应激障碍.本文就以上问题进行了分析,认为外科护士应该评估所有患者在麻醉术中知晓的程度及其影响,认识创伤后应激障碍的诊断标准,从而为患者提供及时、有效的心理辅导和转介咨询.     

单程延迟性应激诱导雌性大鼠创伤后应激障碍模型的建立

目的 采用雌性SD大鼠建立单程长时应激(SPS)模型,从表观效度和预测效度2方面考察其是否能作为创伤性应激障碍的动物模型。方法 雌性大鼠依次连续给予固定束缚(2 h)、强迫游泳(20 min)和乙醚麻醉各1次作为应激因子制备SPS模型,随后连续2周内每天1次ig 给予舍曲林10 mg·kg^-1。2周后给予足底电击刺激,次日环境重现,测定呆滞行为时间;高架十字迷宫实验测定进入开臂次数百分比和开臂滞留时间百分比;开场实验观察爬格次数和站立次数。结果 与正常对照组比较,模型组大鼠呆滞行为时间明显延长(P<0.01),进入开臂次数百分比和开臂滞留时间百分比显著降低(P<0.01);与模型组相比,舍曲林组大鼠呆滞行为时间显著降低,进入开臂次数百分比和开臂滞留时间百分比显著增加(P<0.05, P<0.01); 各组爬格次数和站立数与正常对照组无显著性差异。结论 通过SPS成功诱导建立雌性大鼠创伤性应激障碍动物模型。     

氯胺酮单次注射对创伤后应激障碍模型动物场景恐惧行为的影响及机制

目的在大、小鼠创伤后应激障碍(PTSD)模型上评价氯胺酮单次预防给药对大、小鼠场景恐惧表达的影响,并基于脑源性神经营养因子(BDNF)表达调节研究其作用机制。方法建立小鼠条件性恐惧和大鼠时间依赖性敏化(TDS)2种PTSD动物模型,在条件性恐惧训练前不同时间点进行不同剂量的单次给药,采用僵住行为测试评价氯胺酮在2个模型上对场景恐惧的影响。在小鼠条件性恐惧模型中,训练前0.5 h单次预防性给予氯胺酮10 mg·kg-1,分别于造模训练后24 h和第14天取脑,采用Western印迹法检测大脑皮质BDNF的表达。结果行为学测试结果表明,在小鼠条件性恐惧模型上,氯胺酮10 mg·kg-1分别在训练前第7天、24 h和0.5 h单次预防给药,训练后24 h场景恐惧测试中各组小鼠僵住时间百分率无明显差异;而训练前0.5 h单次预防性ip氯胺酮10 mg·kg-1,在训练后第14天显著降低小鼠僵住时间百分率(P<0.05);在大鼠TDS模型上,条件性恐惧训练前0.5 h单次ip氯胺酮10 mg·kg-1可显著降低TDS大鼠僵住次数百分率(P<0.05)。Western印迹结果显示,在训练后24 h和第14天,与正常对照组相比,模型组小鼠大脑皮质BDNF表达均显著降低(P<0.05);训练前0.5 h给予氯胺酮10 mg·kg-1组,在训练后24 h和第14天小鼠皮质BDNF的表达较模型组均显著升高(P<0.05)。结论氯胺酮单次预防性给药可减少小鼠场景恐惧的表达,该作用与给药剂量有关,且具有延迟起效的特点,但延迟起效作用与恐惧记忆形成后大脑皮质BDNF表达改变在时间上不具有一致性;氯胺酮单次给药可降低TDS增敏的大鼠场景恐惧的表达,此作用与给药时间点密切相关。     

Pharmacotherapy for post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a serious mental illness of considerable importance from a public health perspective. Management of PTSD may involve the use of various treatment modalities, involving both nondrug treatments and pharmacotherapy. Nondrug treatment is regarded as the first-line option for PTSD and should be routinely incorporated into management plans for patients with PTSD. However, some patients do not achieve a sufficient response to nondrug therapy or are left with disabling residual symptoms in one or more areas. Antidepressants are currently the preferred medication for PTSD, with the most substantial evidence available to support the use of the selective serotonin reuptake inhibitors. Many patients with PTSD have symptoms that are resistant to initial drug treatment, meaning that it is often necessary to explore additional pharmacotherapy options to achieve optimal symptom control: antipsychotics, anti-adrenergic drugs, anxiolytics and anticonvulsants have all been advocated as treatments for PTSD. In addition to the management of core PTSD symptoms, it is also necessary for clinicians to address important associated comorbidities, most notably, substance-use disorders and mood disturbances. Interpretation of research studies of the efficacy and safety of PTSD pharmacotherapy is often difficult owing to methodological limitations and factors such as inclusion bias. Further research in fundamental neurosciences and pharmacogenomics may help to elucidate optimal pharmacotherapy options for PTSD in the future.     

Pharmacotherapy for post-traumatic stress disorder: a comprehensive review

Significant advances have been made in the past 5 years in defining efficacious treatments for post-traumatic stress disorder (PTSD). Currently, sertraline is the first and only FDA-approved medication for this complex and often chronic illness. Other serotonergic antidepressants, such as paroxetine, fluoxetine and nefazodone, have well-controlled or replicated open-label evidence of efficacy. Anticonvulsants are also being studied as potential alternatives to treatment. Finally, atypical antipsychotic medications have shown promise in open-label trials. Clearly, more controlled studies are needed. This is especially true in males and in combat trauma-induced PTSD, where the effects of pharmacotherapy are less robust than in females or civilian trauma-induced PTSD. Also, there are virtually no data on pharmacotherapy for acute stress reaction or for PTSD in children. Future directions for research may focus on combination treatment in the more treatment-resistant patient populations.     

Paroxetine in the treatment of post-traumatic stress disorder: pooled analysis of placebo-controlled studies

Post-traumatic stress disorder (PTSD) is increasingly understood to be a medical disorder characterised by particular psychobiological dysfunctions that respond to specific treatments. Paroxetine is a selective serotonin re-uptake inhibitor that has been found effective in the treatment of major depression as well as a range of anxiety disorders. This paper reviews data on the use of paroxetine for the treatment of adult PTSD. There have been three 12-week, placebo-controlled studies of paroxetine in PTSD. As these followed a partly similar design, a pooled analysis of the studies is possible and is reported here. Paroxetine is effective in the short-term treatment of PTSD, resulting in significantly better response and remission rates than placebo, improving sleep disturbance and reducing each of the symptom clusters of PTSD, as well as the disability associated with this condition. The medication is effective in both male and female PTSD patients and whether or not there are comorbid disorders such as depression.     

Alcoholism treatment of Vietnam veterans with post-traumatic stress disorder

Vietnam veterans with alcoholism and Post-Traumatic Stress Disorder (PTSD) are a clinically problematic population. Early self-medication of the PTSD with alcohol led for some to alcohol abuse and dependency. These may often be treated in an intensive alcoholism program. At evaluation both diagnoses are made, and patients are told that alcohol or drug use is not tolerated. The program first focuses on traditional alcoholism treatment issues. Early and consistent support to enhance self-esteem and to reduce guilt helps the patient later to tolerate the gradual investigation of the anger and self-loathing associated with both disorders. Important forces include family and peer support, effective limit setting in a structured milieu, supportive confrontation of alcoholic denial through multidisciplinary treatment in the absence of alcohol. Outpatient follow-up treatment groups include other PTSD sufferers and focus on establishing trust, interweaving the issues of adjustment to sobriety with discussion of the combat experience in a safe, accepting environment, with careful modulation of anxiety by the clinician. Medication must be conservative; benzodiazepines are not used after the detoxification period.     

Review of sertraline in post-traumatic stress disorder

Sertraline (Zoloft?, Pfizer) is a selective serotonin re-uptake inhibitor (SSRI) with proven efficacy in the treatment of post-traumatic stress disorder (PTSD). PTSD is a serious, complex and often chronic mental illness that may follow exposure to a traumatic event. The high prevalence of traumatic events and PTSD in the general population and the resulting distress and dysfunction present a need for the systematic study of the efficacy and effectiveness of treatments for PTSD. Sertraline offers advantages over the older antidepressants, including demonstrated efficacy in PTSD, improved tolerability and low risk of lethality in overdose. Sertraline’s efficacy, favourable tolerability profile and relatively weak effect on the cytochrome P450 system are factors that contribute to make it a first-line agent of choice in the treatment of PTSD.     

Facilitating effect of histamine on spatial memory deficits induced by dizocilpine as evaluated by 8-arm radial maze in SD rats

AIM: To investigate whether or not histamine is involved in spatial memory deficits induced by dizocilpine (MK-801) as evaluated by 8-arm radial maze of rats. METHODS: 8-Arm (4-arm baited) radial maze was used to measure spatial memory in rats. RESULTS: Bilaterally intrahippocampal (ih) injection of MK-801 (0.3 μg/site) impaired working memory and reference memory in rats. Both histamine (50, 100 ng/site, ih) and intraperitoneal (ip) injection of histidine (100, 200 mg/kg) markedly improved the spatial memory deficits induced by MK-801. On the other hand, the ameliorating effect of histidine (100 mg/kg, ip) was completely antagonized by α-fluoromethylhistidine (α-FMH, 5 μg/site, ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H_1-antagonist pyrilamine (1 μg/site, ih), but not by H_2-antagonist cimetidine, even at a high dose (2.5 μg/site, ih). CONCLUSION: The hippocampal histamine plays an important role in the ameliorating effect on MK-801-induced spatial memory deficits,