Orbitofrontal cortex action of 5-hydroxytryptamine and its receptor in an acute forced swimming stress-induced depression model

BACKGROUND： The orbitofrontal cortex （OFC） is a brain region closely associated with emotion. 5-hydroxytryptamine （5-HT） has been shown to be involved in human depression. OBJECTIVE： To investigate OFC actions and mechanisms of 5-HT and 5-HT1A receptor （5-HT1AR） in stress-induced depression.DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at Laboratory of Neurobiology, College of Life Science, Shaanxi Normal University between May 2006 and March 2008. MATERIALS： 5-HT, p-chlorophenylalanine （PCPA, an inhibitor to tryptophan hydroxylase） and spiperone （5-HT1AR antagonist） were provided by Sigma, USA; rabbit anti-rat 5-HT1AR antibody was provided by Tianjin Haoyang Biological Manufacture. METHODS： A total of 40 male Sprague Dawley rats, aged 3 months, were randomly divided into five groups： control, model, 5-HT, spiperone ＋ 5-HT, and PCPA, with 8 rats in each group. Except for control group, rats in the other four groups were used to establish depression models by forced swimming for 15 minutes. At 30 minutes before forced swimming test, 0.5 pL of 5-HT （12.5 pg/pL）, PCPA （20 pg/pL）, spiperone （1.3 pg/pL） ＋ 5-HT （12.5 pg/pL, 10 minutes later）, and saline were respectively injected into the OFC of 5-HT, PCPA, spiperone ＋ 5-HT, and model groups, respectively. The control group received a saline microinjection into the OFC.MAIN OUTCOME MEASURES： Forced swimming and open field tests were employed to measure animal behaviors, and immunohistochemistry was used to analyze 5-HT1AR expression in the OFC, cingulate cortex, and piriform cortex. RESULTS： （1） Compared with the model group, 5-HT microinjection into the OFC prominently reduced immobility time in the forced swimming test and rearing in open field test （P 〈 0.05）; locomotion and grooming in open field test were increased, although there was no significance （P 〉 0.05）. Furthermore, following PCPA microinjection into the OFC （PCPA ＋ forced swimming stress）, immobility time in forced swimming test increased dramatically （P〈 0.01）, locomotion and rearing in open field test declined （P〈 0.05 and P 〈 0.01, respectively）. Compared with the 5-HT group, 5-HT1AR antagonist （spiperone ＋ 5-HT ＋ forced swimming stress） increased immobility time in forced swimming test （P 〈 0.01）, but decreased locomotion, rearing, and grooming in open field test. （2） Forced swimming stress markedly elevated 5-HT1AR expression in OFC, cingulate cortex, and piriform cortex （P〈 0.05 or P〈 0.01）. CONCLUSION： 5-HT improved stress-induced depression, and 5-HT anti-depression effects are primarily achieved via 5-HT1AR. Stress-induced up regulation of 5-HT1AR expression might be a compensatory mechanism for decreased 5-HT expression.

Evaluation of antidepressant activity of methanolic and hydroalcoholic extracts of Acorus calamus L.rhizome through tail suspension test and forced swimming test of mice

Objective:Acorus calamus(AC)L.(Araceae)is an annual semi-aquatic and aromatic plant found in Europe,North America and Asia.Its rhizomes are often used by Native Americans,Americans,and Chinese as well as by other cultures.Ethnobotanical studies and documents have shown their use in various disease treatments,such as insomnia,mental disorders,diabetes mellitus,epilepsy,inflammation,asthma,neuropathic pain,and diarrhea.In this study,the antidepressant activity of methanolic and hydroalcoholic extracts of the AC rhizome part in mice was investigated.Methods:Three doses of methanolic extract of AC rhizome(MEACR)(25,50 and 100 mg/kg b.wt),three doses of hydroalcoholic extract of AC rhizome(HAACR)(100,200 and 400 mg/kg b.wt),and standards(imipramine,15 mg/kg b.wt and fluoxetine,20 mg/kg b.wt)was daily oral administration to the mice for consecutive 14 days.The extract effect on the immobility time was monitored by a tail suspension test(TST)and a forced swimming test(FST).Monoamine oxidase(MAO)levels were also analyzed using standard methods.Results:The optimum antidepressant activity was viewed at 100 mg/kg b.wt of MEACR extract and400 mg/kg b.wt of HAACR extract with 23.82%and 20.59%immobility period reduction,respectively.Besides,the extracts weakened the FST-induced elevation of MAO activity significantly and returned to near-normal levels of neurotransmitters in the brain.100 mg/kg b.wt or above of MEACR extract significantly prevented the MAO-A and MAO-B activities in mice brain at a dose-dependent fashion.But,just 400 mg/kg b.wt of HAACR extract prevented the activity of MAO-A and MAO-B.Fluoxetine and imipramine showed a tendency to prevent the activity of MAO-A and MAO-B.Conclusion:This study suggests that AC rhizome extract mediated antidepressant activity by modulating the central neurochemical and hypothalamic-pituitary-adrenal(HPA)axis in response to FST and TSTinduced stress.Therefore,AC rhizome extract can be used as a valuable plant supplement to treat depressive disorders.

Noradrenergic, glutamatergic and dopaminergic systems are implicated in antidepressant-like effect of flavonoids extracted from okra (Abelmoschus esculentus [L.] Moench.) fruit in the forced swimming test

Okra(Abelmoschus esculentus[L.]Moench.)is one of the most frequently used herbals in East or West Africa,and its various biological activities have been widely studied.Flavonoids extracted from many plants are reported to have neurological properties,e.g antidepressant and antifatigue.However,its neurological protect in antidepressant-like effect of flavonoids extracted from okra have not yet been demonstrated.The present study was aimed at investigating the antidepressant-like eff ect of the flavonoids extracted from okra fruit(FOF)using the forced swimming test(FST)pattern and preliminary exploration its potential mechanism.We also used the open fi eld test(OFT)to estimate the spontaneous locomotor activity.We found that oral administration(p.o.)of FOF(300 mg/kg)alone signifi cantly reduced the immobility time in the FST without changes in locomotor activity in the OPT.The experimental data indicated the antidepressant-like eff ect of FOF involved in noradrenergic,glutamatergic and dopaminergic systems.

Helplessness-like escape deficits of NIH-HS rats predict passive behavior in the forced swimming test:Relevance for the concurrent validity of rat models of depression

The genetically heterogeneous NIH-HS rat stock has been characterized by its response to anxiety- and fear-inducing situations, thus leading to the conclusion that they are a rather anxious and passive coping type of rats. Taking advantage of these profiles, and knowing that they show very poor performance in the two-way active (shuttle box) escape/avoidance task, we have tested NIH-HS rats (n = 80) in the forced swimming test (FST) as well as we have studied escape response deficits (i.e. response failures) of the same animals in the two-way shuttle box task. They were also tested for anxiety in the elevated zero-maze. The goal of such a study was that of investigating whether there are associations or relationships among helplessness-like or passive coping responses between both models of depression, i.e. the FST and the helplessness-like escape deficits in the shuttle box task. The results for the first time show associations among responses from both depression models and that selecting rats for displaying extreme (active or passive) responses in one of the models predict in a coherent manner (according to the hypothesis) their behaviour in the other model. These findings are discussed in the context of the concurrent validity of both models of depression as well as concerning the possible relevance of NIH-HS rats as a tool for future studies on this field.

The Heat-swimming Force on the Fiber-like Particle in Noncon-formity Temperature Fluid

Fiber-like particle suspensions are common in both nature and industry, yet research on them is still in its infancy. This paper focuses on the theoretical analysis of the heat-swimming force operating on the fiber-like particle in nonconformity temperature fluid, and the approximate calculating formula has been proposed. It is indicated that the heat- swimming force on the fiber-like particle is in direct proportion to thetemperature gradient of fluid, but it has opposite direction and that it is restrained by the particle volume, the fluid viscosity and density rather than by the particle density.

甘氨酸对睡眠剥夺小鼠痛阈值及抑郁样行为的影响

目的采用行为学实验探究甘氨酸对睡眠剥夺小鼠痛阈值及抑郁样行为的影响。方法将40只小鼠随机分为4组(n=10):对照+生理盐水组(Control+NS组)、对照+甘氨酸组(Control+Gly组)、睡眠剥夺+生理盐水组(SD+NS组)、睡眠剥夺+甘氨酸组(SD+Gly组)。采用改良多平台法建立睡眠剥夺模型。测定各组小鼠的体重;采用热板法测定各组小鼠的痛阈值;采用强迫游泳实验测定各组小鼠的抑郁样行为。结果①与Control+NS组比较,SD+NS组在第3—5天体重明显下降;SD+Gly组在第3—4天体重明显下降;②与Control+NS组比较,Control+Gly组在第5天痛阈值明显增高,SD+NS组在第5天痛阈值显著降低;与SD+NS组比较,SD+Gly组第5天痛阈值明显增高;③与Control+NS组比较,SD+NS组在第5天漂浮不动时间占总时长的百分比显著增加,SD+Gly组在第5天漂浮不动时间占总时长的百分比显著增加;与SD+NS组比较,SD+Gly组在第5天漂浮不动时间占总时长的百分比明显减少。结论甘氨酸可以提高睡眠剥夺小鼠的痛阈值,并可以缓解睡眠剥夺引起的抑郁样行为。

蓝斑核参与抑郁导致的慢性疼痛行为的调控

目的探究蓝斑核(LC)是否参与介导小鼠抑郁伴疼痛行为及可能机制。方法雄性C57BL/6J小鼠随机分为对照组和慢性束缚应激(CRS)组,通过新奇抑制进食、悬尾和强迫游泳等行为学实验检测抑郁样行为的形成,评估小鼠CRS模型的建立;使用Von Frey毛刷检测小鼠的机械痛阈;通过c-Fos免疫荧光染色确定LC神经元活性在抑郁伴疼痛小鼠中的改变;利用离体脑片电生理检测LC神经元兴奋性变化;通过化学遗传学技术调控LC活性,观察小鼠的疼痛及抑郁样行为表现。结果与对照组相比,CRS小鼠在束缚第3周(CRS 3W)出现明显的抑郁样行为,模型建立成功;CRS 3W小鼠机械痛阈显著下降,出现机械痛敏;CRS 3W小鼠LC区有大量c-Fos+表达,且90%为去甲肾上腺素(NE)能神经元;CRS 3W小鼠LC中NE能神经元兴奋性降低。而且,化学遗传学激活LC可显著缓解CRS 3W小鼠的机械痛敏。结论CRS 3W小鼠LC中NE能神经元兴奋性下降,化学遗传学激活LC中NE能神经元可缓解CRS 3W小鼠的机械痛敏。

Forced swimming stress does not affect monoamine levels and neurodegeneration in rats

Objective The current study was aimed to investigate the correlations between immobility time in the forced swimming test （FST, a behavioral indicator of stress level） and hippocampal monoamine levels （markers of depression）, plasma adrenalin level （a peripheral marker of stress） as well as fluoro-jade C staining （a marker of neurodegeneration）. Methods Male Sprague-Dawley rats were subjected to acute, sub-chronic （7 d） or chronic （14 d） FSTs and immobility time was recorded. Levels of noradrenalin, serotonin and dopamine in the hippocampus, and adrenalin level in the plasma were quantified by high-performance liquid chromatography with electrochemical detection. Brain sections from rats after chronic forced swimming or rotenone treatment （3 mg/kg subcutaneously for 4 d） were stained with fluoro-jade C. Results The rats subjected to swimming stress （acute, sub-chronic and chronic） showed long immobility times [（214 ± 5）, （220 ± 4） and （231 ± 7） s, respectively], indicating that the animals were under stress. However, the rats did not exhibit significant declines in hippocampal monoamine levels, and the plasma adrenalin level was not significantly increased compared to that in unstressed rats. The rats that underwent chronic swimming stress did not manifest fluoro-jade C staining in brain sections, while degenerating neurons were evident after rotenone treatment. Conclusion The immobility time in the FST does not correlate with markers of depression （monoamine levels） and internal stress （adrenalin levels and neurodegeneration）, hence this parameter may not be a true indicator of stress level.

脑血流剪切力作用机制下的游泳训练对HIE患儿康复效果分析

目的 通过回顾性分析探讨脑血流剪切力作用机制下游泳训练对新生儿缺血缺氧脑病(hypoxia ischemic encephalopathy,HIE)患儿康复效果.方法 选取64例HIE患儿为研究对象,在常规治疗康复手段基础上参与游泳的患儿为观察组(n=31例),未参与的为对照组(n=33例);对照组采用常规治疗及护理方案,观察组患儿在常规方案基础上,出生7 d后参与保健院的游泳训练,比较两组患儿NBNA评分及DDST筛查结果.结果 与对照组比较,观察组患儿28 d的行为能力、被动肌张力、主动肌张力、原始反射、一般评估和总得分均有所提高;6个月、8个月和12个月的DDST筛查阳性率下降(P<0.05).结论 脑血流剪切力作用机制下游泳训练可在一定程度上改善HIE患儿的神经行为和智能发育.

运动对慢性不可预测轻度应激模型鼠抑郁样行为的干预作用:系统综述和Meta分析

目的:抑郁症是全球疾病负担的五大主要原因之一,目前可用的抗抑郁药物疗效低、起效慢、不良反应严重,而运动是治疗抑郁症的一种较好的方式。文章系统评价了运动对慢性不可预知轻度应激(CUMS)模型鼠抑郁相关行为的干预效果。方法:检索万方、中国知网、PubMed、Embase和Web of Science数据库,检索文献时限为2000-01-01/2022-02-28,收集跑台、游泳、转轮等运动对慢性不可预知轻度应激(CUMS)抑郁动物模型强迫游泳、悬尾、糖水偏好行为学影响的研究。由2位研究者按照纳入标准独立完成文献筛选、资料提取及SYRCLE动物实验偏倚风险评估工具进行方法学质量评价,运用RevMan 5.3和Stata 13.0分析软件进行统计分析。结果:共纳入23篇对照动物实验文献,运动组实验动物301只,对照组302只。Meta分析结果显示:①运动能够显著降低抑郁模型鼠强迫游泳测试潜伏期[SMD=-3.93,95%CI:(-4.88,-2.98),P<0.00001]及悬尾测试潜伏期[SMD=-4.42,95%CI:(-5.62,-3.23),P<0.00001];②运动同样可以提高糖水偏好指数[SMD=2.37,95%CI:(1.62,3.11),P<0.00001];③悬尾测试中对运动方式进行亚组分析可以降低异质性[SMD=-3.68,95%CI:(-4.16,-3.21),P<0.00001],但并不影响运动效果。结论:运动能有效改善慢性不可预知轻度应激(CUMS)模型鼠强迫游泳、悬尾、糖水偏好的抑郁样行为。运动方式可能是影响悬尾测试行为的异质性来源;造模时间、干预阶段、运动方式及运动时间不是影响运动改善抑郁效果的主要因素。

模拟失重不同时长对大鼠抑郁样行为的影响

目的本研究旨在观察不同持续时间的模拟失重对大鼠抑郁样行为和海马超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的影响,以探究其影响及可能的作用机制。方法采用后肢悬挂(HLS)尾吊法模拟大鼠失重状态。将大鼠分为对照组和不同模拟失重时间尾吊组(尾吊时长分别为1、2、3、4周)。采用旷场实验(OFT)、新物体识别实验(NORT)、强迫游泳实验(FST)观察大鼠抑郁样行为,采用酶联免疫吸附试验(ELISA)法测定海马SOD和CAT活性。结果OFT结果显示,与对照组相比,HLS不同时间大鼠的僵滞时间增加(P<0.05,P<0.01)。在NORT中,与对照组相比,HLS不同时间大鼠对新物体的探索潜伏期增加,探索次数和时间减少(P<0.05,P<0.01)。在FST中,与对照组相比,HLS不同时间大鼠在FST中的不动时间增加,攀爬次数减少(P<0.05,P<0.01)。与对照组相比,HLS不同时间组大鼠海马组织中SOD和CAT水平均下降(P<0.05,P<0.01)。结论短时间或长时间的失重都会导致大鼠产生类抑郁样行为。

出生前糖皮质激素暴露对子代大鼠情感行为障碍影响的研究

目的 揭示出生前暴露于糖皮质激素对子代大鼠情感行为障碍的影响。方法 将孕鼠随机分为2组,实验组在孕15.5 d,每天给予0.15 mg·mL^(-1)地塞米松0.1 mL,对照组注射0.1 mL生理盐水直至生产。记录子代成年大鼠强迫游泳实验上窜时间及不动时间;使用微透析方法检测中缝核5-HT含量和qRT-PCR方法检测Bcl-2 mRNA与Bax mRNA表达情况。结果 与对照组相比,实验组强迫游泳实验不动时间明显延长,上窜时间明显缩短(P <0.01);中缝核内5-HT的含量明显减少(P <0.01);Bcl-2/Bax mRNA比值较低(P <0.01)。结论 出生前糖皮质激素的暴露,导致了成年后子代抑郁行为的改变,这种改变可能是通过诱发中缝核神经元细胞凋亡和神经递质5-HT含量的减少引起。

Flavonoid-rich fraction of the Monodora tenuifolia seed extract attenuates behavioural alterations and oxidative damage in forced-swim stressed rats

The antidepressant effects of the flavonoid-rieh fraction of Monodora tenuifolia seed extract were examined by assess- ing the extent of attenuation of behavioural alterations and oxidative damage in the rats that were stressed by forced swim test. Com- pared with the model control group, the altered behavioural parameters were attenuated significantly （P 〈 0.05） in the group treated with the flavonoid-rich fraction （100 and 200 mg·kg^-1）, comparable to the group treated with the standard drug, fluoxetine （10 mg·kg^-1）. The flavonoid-rich fraction and fluoxetine improved significantly （P 〈 0.05） the activities of the antioxidant enzymes such as superoxide dismutase and catalase as well as other biochemical parameters such as reduced glutathione, protein, and nitrite in the brain of the stressed rats. These results suggested that the flavonoid-rich fraction of Monodora tenuifolia seed extract exerted the antidepres- sant-like effects which could be useful in the management of stress induced disease.

A study of the effects of 3,5-diiodo-L-thyronine in the tail suspension and forced swim models of depression

Objectives: Recent findings have further highlighted the role of the thyroid system in the pathophysiology of depression and revealed new physiologically relevant elements of the thyroid system. Our previous study showed an antidepressant-like effect of 3,5-diiodo-L-thyronine(T2), which was previously considered to be a physiologically inactive molecule, in mice. Here, we aimed to investigate the antidepressant-like effects of T2 further. Methods: We studied the effects of bolus injections of T2 to C57Bl6 J mice at doses of 0.25 or 0.75 mg/kg with the tail suspension and forced swim models. The effects of the higher dose were investigated in CD1 mice in the forced swim test. Potential behavioral effects of these treatments were also studied using the novel cage and dark-light box tests.Results: A reduction of depressive-like behavior was found in mice treated with 0.75 mg/kg of T2 in the tail suspension test, but not in the forced swim test. Locomotion and anxiety variables were unaltered following treatment with T2. There were no significant changes after bolus administration of 0.25 mg/kg T2 in either test for depressive-like behavior. Thus, bolus injection of T2 at the dose 0.75 mg/kg can induce antidepressant-like effects without affecting other behaviors. Conclusions: A discrepant result in the forced swim test may be due to its different sensitivity to T2 compared with the tail suspension paradigm. Furthermore, the development of procedural modifications of this model can be useful in its application in pre-clinical studies.

游泳运动技术优化与创新的研究

运用运动生物力学、流体力学、程序设计等研究方法,为游泳技术研究提供了一个多元化的诊断方法,提出了游泳技术训练与技术研究可操作的程序化模式,搭建了游泳技术研究与高科技结合的应用渠道,保障了重点运动员的技术训练与技术研究。在研究方法和应用实践研究方面具有一定的创新性。

昆明小鼠强迫游泳实验与悬尾实验抑郁模型相关性

目的探讨强迫游泳实验(FST)和悬尾实验(TST)作为昆明小鼠抑郁动物模型的相关性。方法成年雄性昆明小鼠先后进行TST和FST,摄像系统分别记录6 min内的行为变化,实验间隔1周,实验参数有不动状态潜伏期和不动状态持续时间百分率;采用因子分析、聚类分析、相关分析、一致性检验和生存分析等多种统计方法进行数据处理。结果①因子分析提示,FST与TST参数分别反映了FST与TST 2种不同抑郁模型维度。②聚类分析提示,不动状态潜伏期参数反映了抗抑郁状态,不动状态持续时间百分率反映了抑郁样绝望行为;经过适当数据转换后,FST与TST参数分别反映了FST与TST 2种不同抑郁模型维度。③相关分析结果提示,FST与TST参数组内具有较好相关性,而组间不动状态潜伏期参数相关性尚可。④一致性检验ICC统计参数提示,FST与TST参数评价抑郁样绝望行为一致性均较差;Kappa统计参数提示,不动状态潜伏期可作为FST与TST评价抑郁样绝望行为一致性的稳定参数。⑤生存分析提示,FST与TST的不动状态潜伏期参数半数生存期差异有统计学意义,即FST与TST实验操作对实验动物首次产生抑郁样绝望行为的效力不同,且FST<TST。结论 FST与TST参数反映了2种不同抑郁模型维度;不动状态潜伏期是FST与TST评价抑郁样绝望行为一致性及首次产生抑郁样绝望行为效力的稳定参数;FST与TST联合进行抗抑郁药物评价时,应注意动物模型异质性问题。

积雪草总苷对小鼠抑郁行为和脑内氨基酸含量的影响

目的:采用小鼠强迫游泳抑郁症模型,观察积雪草总苷的抗抑作用。;方法:昆明种小鼠随机分为空白对照组、模型组、阳性对照丙咪嗪组和积雪草总苷组,分析药物对小鼠强迫游泳不动时问及脑内氨基酸含量的影响结果:丙咪嗪组和积雪草总苷低、中、高3个剂量能够显著缩短小鼠强迫游泳不动时间,改善强迫游泳所致小鼠脑内氨基酸含量的失调。结论:积雪草总苷具有抗抑郁活性。

维生素C对应激大鼠脑内超氧化物歧化酶含量的影响

目的 :探讨在急性应激状态下大鼠脑内超氧化物歧化酶 (SOD)活性的变化及维生素C (VitC)对SOD改变的影响。方法 :在强迫游泳应激模型中 ,大鼠用VitC慢性给药 (腹腔内注射 0 5g·Kg- 1 ,每日一次 ,连续 7天 ) ,观察强迫游泳应激后大鼠额叶、海马、中脑和下丘脑内SOD的活性。结果 :与对照组比较 ,强迫游泳组大鼠海马内SOD活性显著性增高 (t=3 3 2 4,P <0 0 1) ,额叶、中脑和下丘脑SOD活性也显著升高 (t =2 5 3 3 ,2 3 0 3 ,2 5 89,P均 <0 0 5 )。VitC组与对照组各脑区SOD活性未见明显变化 (P均 >0 0 5 ) ;但与强迫游泳组比较 ,海马内SOD活性显著性降低 (t=3 812 ,P <0 0 1) ,额叶、中脑和下丘脑内SOD活性也显著性降低 (t=2 2 5 1,2 3 42 ,2 2 16,P均 <0 0 5 )。结论 :VitC可显著减少急性应激状态下脑内产生的自由基 ,具有神经保护作用。

电针合用抗抑郁药能明显减少小鼠强迫游泳实验中的静止时间

目的 :本实验采用小鼠强迫游泳实验的方法 ,观察针刺合用抗抑郁药后小鼠在水中的静止时间 ,以此来分析抑郁程度的改善情况。方法 :实验分下列各组 :①生理盐水组 ;②电针加生理盐水组 ;③药物组 ,分别观察了氯丙咪嗪 (氯米帕明 2 .5mg/kg、5mg/kg、1 0mg/kg、2 0mg/kg、60mg/kg)、芬氟明 ( 1 .5mg/kg、3mg/kg、1 2mg/kg)和吗氯贝胺 ( 1 0mg/kg、2 0mg/kg、40mg/kg)等三种药物的作用 ;④上述药物加电针组。结果 :电针能使小鼠在水中静止的时间显著减少 ,腹腔注射 (ip)上述三种药物也能减少小鼠在水中静止的时间 ,并表现出一定的剂量依赖关系。在电针加药组中 ,分别选用三种药物的小剂量 (抗抑郁效果很弱或几乎无效 )与电针合用。氯丙咪嗪( 2 .5mg/kg)、芬氟明 ( 1 .5mg/kg)与电针合用后 ,小鼠在水中静止时间与单用药物组或单电针组相比显著减少。而吗氯贝胺 ( 1 0mg/kg)与电针合用虽也有这种趋势 ,但统计学上尚未达到显著性差异。结论 :电针具有抗抑郁作用 。