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.

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.

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.

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.

Where is the rudder of a fish?:the mechanism of swimming and control of self-propelled fish school

Numerical simulation and control of self- propelled swimming of two- and three-dimensional biomimetic fish school in a viscous flow are investigated. With a parallel computational fluid dynamics package for the two- and three-dimensional moving boundary problem, which combines the adaptive multi-grid finite volume method and the methods of immersed boundary and volume of fluid, it is found that due to the interactions of vortices in the wakes, without proper control, a fish school swim with a given flap- ping rule can not keep the fixed shape of a queue. In order to understand the secret of fish swimming, a new feedback con- trol strategy of fish motion is proposed for the first time, i,e., the locomotion speed is adjusted by the flapping frequency of the caudal, and the direction of swimming is controlled by the swinging of the head of a fish. Results show that with this feedback control strategy, a fish school can keep the good order of a queue in cruising, turning or swimming around circles. This new control strategy, which separates the speed control and direction control, is important in the construction of biomimetic robot fish, with which it greatly simplifies the control devices of a biomimetic robot fish.

Quantization of the 1-D Forced Harmonic Oscillator in the Space (<i>x</i>, <i>v</i>)

The quantization of the forced harmonic oscillator is studied with the quantum variable (x, v∧), with the commutation relation , and using a Schrödinger’s like equation on these variable, and associating a linear operator to a constant of motion K (x, v, t) of the classical system, The comparison with the quantization in the space (x, p) is done with the usual Schrödinger’s equation for the Hamiltonian H(x, p, t), and with the commutation relation . It is found that for the non-resonant case, both forms of quantization bring about the same result. However, for the resonant case, both forms of quantization are different, and the probability for the system to be in the exited state for the (x, v∧) quantization has fewer oscillations than the (x, p∧) quantization, the average energy of the system is higher in (x, p∧) quantization than on the (x, v∧) quantization, and the Boltzmann-Shannon entropy on the (x, p∧) quantization is higher than on the (x, v∧) quantization.

Pressure Gradient Force,Saffman Lift,and Magnus Lift on the Fiber-like Particle in Fluid

Flher-like particle suspensions are common in both na-ture and industry, but there is little work reported on it.The forces acting on the fiber - like particle in fluid arestudied in this paper, and the Magnus lift, Saffman lift,pressure gradient force, and then the dynamics modelhave been received. The numerical study of the simpleshear flow past the cylinders shows that the particles ’motion is controlled by the vortex.

Reducing force transmissibility in multiple degrees of freedom structures through anti-symmetric nonlinear viscous damping

In the present study, the Volterra series theory is adopted to theoretically investigate the force transmissibility of multiple degrees of freedom （MDOF） structures, in which an isolator with nonlinear anti-symmetric viscous damping is assembled. The results reveal that the anti-symmetric nonlinear viscous damping can significantly reduce the force trans- missibility over all resonance regions for MDOF structures with little effect on the transmissibility over non-resonant and isolation regions. The results indicate that the vibration isolators with an anti-symmetric damping characteristic have great potential to solve the dilemma occurring in the design of linear viscously damped vibration isolators where an increase of the damping level reduces the force transmissibility over resonant frequencies but increases the transmissibility over non-resonant frequency regions. This work is an extension of a previous study in which MDOF structures installed on the mount through an isolator with cubic nonlinear damping are considered. The theoretical analysis results are also verified by simulation studies.

Numerical Analysis of the Adhesive Forces in Nano-Scale Structure

Nanohairs, which can be found on the epidermis of Tokay gecko＇s toes, contribute to the adhesion by means of van der Waals force, capillary force, etc. This structure has inspired many researchers to fabricate the attachable nano-scale structures. However, the efficiency of artificial nano-scale structures is not reliable sufficiently. Moreover, the mechanical parameters related to the nano-hair attachment are not yet revealed qualitatively. The mechanical parameters which have influence on the ability of adhesive nano-hairs were investigated through numerical simulation in which only van der Waals force was considered. For the numerical analysis, finite element method was utilized and van der Waals force, assumed as 12-6 Lennard-Jones potential, was implemented as the body force term in the finite element formulation.

Investigation on 3Dt wake flow structures of swimming bionic fish

A bionic experimental platform was designed for the purpose of investigating time accurate three-dimensional flow field, using digital particle image velocimetry （DSPIV）. The wake behind the flapping trail of a robotic fish model was studied at high spatial resolution. The study was performed in a water channel. A robot fish model was designed and built. The model was fixed onto a rigid support frame- work using a cable-supporting method, with twelve stretched wires. The entire tail of the model can perform prescribed motions in two degrees of freedom, mainly in carangiform mode, by driving its afterbody and lunate caudal fin respectively. The DSPIV system was set up to operate in a trans- lational manner, measuring velocity field in a series of parallel slices. Phase locked measurements were repeated for a number of runs, allowing reconstruction of phase average flow field. Vortex structures with phase history of the wake were obtained. The study reveals some new and complex three-dimensional flow structures in the wake of the fish, including ＂reverse hairpin vortex＂ and ＂reverse Karman S-H vortex rings＂, allowing insight into physics of this complex flow.

An integrated approach for the optimization of wheel-rail contact force measurement systems

A comprehension of railway dynamic behavior implies the measure of wheel-rail contact forces which are affected by disturbances and errors that are often difficult to be quantified. In this study, a benchmark test case is proposed, and a bogie with a layout used on some European locomotives such as SIEMENS El90 is studied. In this layout, an additional shaft on which brake disks are installed is used to transmit the braking torque to the wheelset through a single-stage gearbox. Using a mixed approach based on finite element techniques and statistical considerations, it is possible to evaluate an optimal layout for strain gauge positioning and to optimize the measurement system to diminish the effects of noise and disturbance. We also conducted preliminary evaluations on the precision and frequency response of the proposed system.

Steady vortex force theory and slender-wing flow diagnosis

The concept vortex force in aerodynamics is sys- tematically examined based on a new steady vortex-force theory （Wu et al., Vorticity and vortex dynamics, Springer, 2006） which expresses the aerodynamic force （and moment） by the volume and boundary integrals of the Lamb vector. In this paper, the underlying physics of this theory is explored, including the general role of the Lamb vector in non- linear aerodynamics, its initial formation, and its relevance to the total-pressure non-uniformity. As a typical example, the theory is applied to the flow over a slender delta wing at a large angle of attack. The highly localized flow structures with high Lamb-vector peaks are identified in terms of their net contribution to various constituents of the total aerody-namic force. This vortex-force diagnosis sheds new light on the flow control and configuration optimization.

抑郁模型大鼠杏仁核神经元凋亡及Bax/Bcl-2的变化

目的:探讨抑郁模型大鼠杏仁核神经元凋亡现象。方法:将成年健康雄性Wistar大鼠随机分为对照组(15只)和模型组(15只)。采用慢性强迫游泳(4周)制备慢性强迫游泳应激抑郁模型。采用TUNEL和流式细胞术检测杏仁核神经元凋亡和凋亡率,WesternBlot检测凋亡相关蛋白Bax/Bcl-2的表达变化。结果:模型组和对照组凋亡细胞阳性率分别为24.08±4.30和3.08±0.91,凋亡率分别为17.14±2.71和3.34±0.80,Bax/Bcl-2比值分别为1.73±0.15和0.92±0.07,差异均有统计学意义(P<0.01)。结论:抑郁模型大鼠杏仁核存在明显的神经元凋亡,这可能是抑郁患者杏仁核体积异常的原因之一。

慢性应激对大鼠海马Bcl-xl表达的影响及应激后的变化

目的:探讨慢性应激对大鼠海马神经元Bcl-xl蛋白表达的影响及其应激后的变化。方法:采用慢性强迫冰水游泳制作动物模型。运用open-field法观察大鼠行为学的变化,运用免疫组织化学方法观察大鼠海马DG区、CA3区Bcl-xl的变化。结果:与对照组相比,实验组1大鼠海马CA3区齿状回(DG)区Bcl-xl平均灰度值显著增加(t=4.69,P<0.05和t=3.77,P<0.01),实验组2平均灰度值与对照组2相比同样增加(t=3.35,P<0.05和t=3.30,P<0.05)。结论:慢性应激使大鼠海马Bcl-xl表达降低,应激三十天后,其表达仍低于对照组。

改善氧化应激平衡和逆转NET及5-HTT表达异常涉及文拉法辛的抗抑郁作用

目的探讨文拉法辛抗慢性不可预见刺激所致大鼠抑郁症作用与氧化应激和海马去甲肾上腺素转运体(norepinephrine transporter,NET)、5羟色胺转运体(serotonin transporter,5-HTT)表达的关系。方法♂SD大鼠80只,根据开场实验得分分为4组,即正常对照组(NG)、模型组(MG)、文拉法辛处理的正常对照组(VNG)和文拉法辛处理的模型组(VMG)。采用孤养结合慢性不可预见刺激(chronic unpredictable stress,CUS)方法建立大鼠抑郁模型;给药组每天给予文拉法辛(23.4 mg·kg-1·d-1),NG和MG组每天给予同体积溶剂。采用强迫游泳(force swimming)实验评价大鼠的抑郁行为,生物化学方法检测大鼠血清的超氧化物岐化酶(superoxide dismutase,SOD)活性与丙二醛(malondialdehyde,MDA)含量,实时定量RT-PCR分析海马5-HTT、NET的mRNA表达,Western blot测定海马5-HTT、NET的蛋白表达。结果相对于NG组,MG组大鼠在强迫游泳实验中的不动时间明显增加,SOD活性降低,血清MDA含量升高,海马5-HTT表达明显下降,而NET的表达明显升高。文拉法辛干预能阻遏CUMS诱导的上述变化;文拉法辛处理对正常对照大鼠的行为、SOD、MDA和5-HTT及NET表达无明显影响。结论文拉法辛抑制CUS诱导大鼠出现焦虑抑郁样行为的机制至少部分与其改善脑内氧化应激平衡,逆转5-HTT和NET异常表达有关。

电针对慢性强迫游泳应激模型大鼠抑郁样行为及血清5-HT的影响

目的:在慢性强迫游泳应激模型上,观察电针对大鼠行为及血清五羟色胺(5-HT)含量的影响。方法:将雄性SD大鼠随机分为正常对照组、模型组、电针组和氟西汀组,每组10只。采用慢性强迫游泳应激方法制备抑郁大鼠模型。通过体质量、旷场实验、糖水实验对大鼠进行行为学评价,用ELISA方法检测大鼠血清中的5-HT含量。结果:与正常组比较,模型组大鼠体质量、旷场实验的水平运动和垂直运动次数、糖水摄入量均明显下降(P<0.05),血清5-HT含量降低(P<0.05)。与模型组比较,电针组和氟西汀组大鼠体质量、旷场实验中的平行活动和垂直运动次数、糖水摄入量均明显增加(P<0.05),血清中的5-HT含量明显增加(P<0.05),电针组与氟西汀组之间比较,无显著性差异(P>0.05)。结论:电针可改善慢性强迫游泳应激导致的大鼠抑郁样行为异常,明显增加血清中5-HT含量,具有抗抑郁作用。