The impurity transport in HT-6M tokamak

International Nuclear Information System (INIS)

Xu Wei; Wan Baonian; Xie Jikang

2003-01-01

The space-time profile of impurities has been measured with a multichannel visible spectroscopic detect system and UV rotation-mirror system in the HT-6M tokamak. An ideal impurity transport code has been used to simulate impurities (carbon and oxygen) behaviour during the OHM discharge. The profiles of impurities diffusion and convection coefficient, impurities ion densities in different ionized state, loss power density and effective charge number have been derived. The impurity behaviour during low-hybrid current drive has also been analyzed, the results show that the confinement of particles, impurities and energy has been improved, and emission power and effective charge number have been reduced

Power supply system on HT-7 tokamak for diagnostic neutral beam based on PLC

International Nuclear Information System (INIS)

Zhang Jian; Liu Baohua; Ding Tonghai; Du Shaowu

2006-01-01

A power supply system for diagnostic neutral beam on the HT-7 Tokamak was developed. Its logic control system based on S7-300 PLC was described. The experimental results show that the system is easy to operate and its performance is reliable. (authors)

Application of avalanche photodiode for soft X-ray pulse-height analyses in the Ht-7 tokamak

CERN Document Server

Shi Yue Jiang; Hu Li Qun; Sun Yan Jun; LiuSheng; Ling Bil

2002-01-01

An avalanche photodiode (APD) has been used as soft X-ray energy pulse-height analysis system for the measurement of the electron temperature on the HT-7 tokamak. The experimental results obtained with the APD with its inferior energy resolution show a little difference compared to the conventional high energy-resolution Si (Li) detector. Both numerical analysis and experimental results prove that the APD is good enough for application of the electron temperature measurement in tokamaks.

Electron Heating of LHCD Plasma in HT-7 Tokamak

International Nuclear Information System (INIS)

Ding Yonghua; Wan Baonian; Lin Shiyao; Chen Zhongyong; Hu Xiwei; Shi Yuejiang; Hu Liqun; Kong Wei; Zhang Xiaoqing

2006-01-01

Electron heating via lower hybrid current drive (LHCD) has been investigated in HT-7 superconducting tokamak. Experiments show that the central electron temperature T e0 , the volume averaged electron temperature e > and the peaking factor of the electron temperature Q Te = T e0 / e > increase with the lower hybrid wave (LHW) power. Simultaneously the electron heating efficiency and the electron temperature as the function of the central line-averaged electron density (n e ) and the plasma current (I p ) have also been investigated. The experimental results are in a good agreement with those of the classical collision theory and the LHW power deposition theory

Investigation of sawtooth behavior and confinement property with RHF on the HT-6B tokamak

International Nuclear Information System (INIS)

Hao Yuping; Xie Jikang; Li Linzhong

1989-01-01

The experiment results of the resonant helical field (RHF) effects on plasma confinement and sawtooth behavior on the HT-6B Tokamak are presented. The RHF makes decrease of electron thermal conductivity, broadening of temperature profile, increase of plasma density and enhancement of impurity radiation, in meanwhile intensification of sawtooth oscillation (in amplitude, period, rising slope and invert radius) and suppression of m = 2, 3, 4 modes. It is shown that the discharge transforms to a new discharge condition

Measurement on the emission of charge exchange recombination in HT-6M tokamak

International Nuclear Information System (INIS)

Xu Wei; Wan Baonian

1999-01-01

The distribution of C VI line (at 207.1 nm) and the time behavior has been measured with Optical Spectroscope Multichannel Analyzer and single channel near ultra-violet system in HT-6M Tokamak. The result of the analysis of line shape and the time behavior show that C VI line (at 207.1 nm) stemmed from the emission of charge exchange recombination processes

Upgraded data service system for HT-7 tokamak

International Nuclear Information System (INIS)

Qu Lianzheng; Luo Jiarong; Wei Peijie; Li Guiming; Cheng Ting; Qi Na

2005-01-01

A data service system plays an indispensable role in HT-7 Tokamak experiment. Since the former system doesn't provide the function of timely data procession and analysis, and all client software are based on Windows, it can't fulfill virtual fusion laboratory for remote researchers. Therefore, a new system which is simplified by three kinds of data servers and one data analysis and visualization software tool has been developed. The data servers include a data acquisition server based on file system, an MDSplus server used as the central repository for analysis data, and a web server. Users who prefer the convenience of application that can be run in a Web Browser can easily access the experiment data without knowing X-Windows. In order to adjust instruments to control experiment the operators need to plot data duly as soon as they are gathered. To satisfy their requirement, an upgraded data analysis and visualization software GT-7 is developed. It not only makes 2D data visualization more efficient, but also it can be capable of processing, analyzing and displaying interactive 2D and 3D graph of raw, analyzed data by the format of ASCII, LZO and MDSplus. (authors)

Investigation of the LH wave energy conversion and current drive efficiency in the HT-7 tokamak

International Nuclear Information System (INIS)

Chen, Z.Y.; Wan, B.N.; Shi, Y.J.; Lin, S.Y.; Hu, L.Q.; Asif, M.

2005-01-01

Lower hybrid current drive (LHCD) plasmas in the presence of DC electric filed have been investigated based on Karney-Fisch theory in the HT-7 tokamak. The relatively small scatter in the experimental data with various values of waveguide phasing and lower hybrid power, when plotted in the Karney-Fisch diagram, confirms that a reasonable theoretical interpretation is possible for the HT-7 data. The full non-inductively current drive efficiencies are obtained by fitting the experimental data to the theoretical curve. The efficiency strongly depends on the lower hybrid wave phase velocity

Experiments in the HT-7 Superconducting Tokamak

International Nuclear Information System (INIS)

Wan Baonian

2002-01-01

The HT-7 tokamak experiment research has made important progress. The main efforts have dealt with quasi-steady-state operation, lower-hybrid (LH) current drive (LHCD), plasma heating with ion cyclotron range of frequencies (ICRF), ion Bernstein waves (IBWs), fueling with pellets and supersonic molecular beams, first-wall conditioning techniques, and plasma and wall interaction. Plasma parameters in the experiments were much improved; for example, n e = 6.5 x 10 19 m -3 , and a plasma pulse length of >10 s was achieved. ICRF boronization and conditioning resulted in Z eff close to unity. Steady-state full LH wave current drive has been achieved for >3 s. LHCD rampup and recharge have also been demonstrated. The best [eta] CD exp of 10 19 m -2 A/W is achieved. Quasi-steady-state H-mode-like plasmas with a density close to the Greenwald limit were obtained by LHCD, where energy confinement time was nearly five times longer than in the ohmic case. The synergy between the IBW, pellet, and LHCD was investigated. New doped graphite as limiter material and ferritic steel used to reduce the ripples have been developed. Research on the mechanism of microturbulence has been extensively carried out experimentally

Vertical one-dimensional electron cyclotron emission imaging diagnostic for HT-7 tokamak

International Nuclear Information System (INIS)

Wang Jun; Xu Xiaoyuan; Wen Yizhi; Yu Changxuan; Wan Baonian; Luhmann, N.C.; Wang, Jian; Xia, Z.G.

2005-01-01

A vertical resolved 16-channel electron cyclotron emission imaging (ECEI) diagnostic has been developed and installed on the HT7 Tokamak for measuring plasma electron cyclotron emission with a temporal resolution of 0.5 us. The system is working on a fixed frequency 97.5 GHz in the first stage. The sample volumes of the system are aligned vertically with a vertical channel spacing of 11 mm, and can be shifted across the plasma cross-section by varying the toroidal magnetic field. The high spatial resolution of the system is achieved by utilizing a low cost linear mixer/receiver array and an optical imaging system. The focus location may be shifted horizontally via translation of one of the optical imaging elements. The detail of the system design and laboratory testing of the ECE Imaging optics are presented, together with HT7 plasma data. (author)

Ion Bernstein wave heating experiments in HT-7 superconducting tokamak

International Nuclear Information System (INIS)

Zhao Yanping

2005-01-01

Ion Bernstein Wave (IBW) experiments have been carried out in recent years in the HT-7 superconducting Tokamak. The electron heating experiment has been concentrated on deuterium plasma with an injecting RF power up to 350 kw. The globe heating and localized heating can be seen clearly by controlling the ICRF resonance layer's position. On-axis and off-axis electron heating have been realized by properly setting the target plasma parameters. Experimental results show that the maximum increment in electron temperature has been more than 1 keV, the electron temperature profile has been modified by IBW under different plasma conditions, and both energy and particle confinement improvements have been obtained. (author)

Analysis of Electron Thermal Diffusivity and Bootstrap Current in Ohmically Heated Discharges after Boronization in the HT-7 Tokamak

International Nuclear Information System (INIS)

Zhang, X.M.; Wan, B.N.

2005-01-01

Significant improvements of plasma performance after ICRF boronization have been achieved in the full range of HT-7 operation parameters. Electron power balance is analyzed in the steady state ohmic discharges of the HT-7 tokamak. The ratio of the total radiation power to ohmic input power increases with increasing the central line-averaged electron density, but decreases with plasma current. It is obviously decreased after wall conditioning. Electron heat diffusivity χ e deduced from the power balance analysis is reduced throughout the main plasma after boronization. χ e decreases with increasing central line-averaged electron density in the parameter range of our study. After boronization, the plasma current profile is broadened and a higher current can be easily obtained on the HT-7 tokamak experiment. It is expected that the fact that the bootstrap current increases after boronization will explain these phenomena. After boronization, the plasma pressure gradient and the electron temperature near the boundary are larger than before, these factors influencing that the ratio of bootstrap current to total plasma current increases from several percent to above 10%

Propagation of Blob in boundary of HT-7 tokamak

International Nuclear Information System (INIS)

Yan Ning; Zhang Wei; Chang Jiafeng; Ming Tingfeng; Ding Siye

2011-01-01

Intermittent characteristics of turbulence induced by coherent structures (Blob) are manifested clearly on the Langmuir probe signal of HT-7 tokamak. With conditional analysis, asymmetric characteristics of the intermittent bursts are demonstrated. The parameter of plasma inside the Blob is larger than the background plasma parameter. Due to the radial propagation of the coherent structures, the particle density and temperature profiles in the scrape-off layer (SOL) are non-exponential and flat away from the last closed flux surface (LCFS). Around the LCFS, large burst fluctuations are responsible for about 50% of the total transport. These experimental finds may imply that the coherent structures are distorted by the developed shear flow in the shear layer. In SOL region, the coherent structures propagate in the direction of ion diamagnetic drift. (authors)

Preliminary experiment results of EOH in HT-6M tokamak

Energy Technology Data Exchange (ETDEWEB)

Yuedong, Meng; Jiangang, Li; Xiang, Gao [Academia Sinica, Hefei, AH (China). Inst. of Plasma Physics

1994-04-01

Confinement improvement over normal ohmic level has been achieved in HT-6M tokamak by current ramp up at the rate of 12 Ma/s. After the current ramp up, the H{sub {alpha}} drops and electron temperature becomes peak profile. The plasma current increases about 10% and edge plasma density increases quite a lot (more than 50%) after the ramp up and then becomes peaking later on. Radiation loss is reduced and its profile becomes broad. Corresponding to different density range, the MHD behaviour changes from strong m = 3 and m 2 Mirnov oscillations to weak ones, Mirnov oscillation to sawtooth oscillation and small quick sawtooth to large slow ones. The energy confinement time increases about 1.6 to 1.9 times and particle confinement time increases about a factor of four. The detail current penetration process is analysed and compared to classical diffusion process. All of these phenomena is very similar to the L-H transition.

Preliminary experiment results of EOH in HT-6M tokamak

International Nuclear Information System (INIS)

Meng Yuedong; Li Jiangang; Gao Xiang

1994-04-01

Confinement improvement over normal ohmic level has been achieved in HT-6M tokamak by current ramp up at the rate of 12 Ma/s. After the current ramp up, the H α drops and electron temperature becomes peak profile. The plasma current increases about 10% and edge plasma density increases quite a lot (more than 50%) after the ramp up and then becomes peaking later on. Radiation loss is reduced and its profile becomes broad. Corresponding to different density range, the MHD behaviour changes from strong m = 3 and m 2 Mirnov oscillations to weak ones, Mirnov oscillation to sawtooth oscillation and small quick sawtooth to large slow ones. The energy confinement time increases about 1.6 to 1.9 times and particle confinement time increases about a factor of four. The detail current penetration process is analysed and compared to classical diffusion process. All of these phenomena is very similar to the L-H transition

The resonance between runaway electrons and magnetic ripple in HT-7 Tokamak

International Nuclear Information System (INIS)

Zhou Ruijie; Hu Liqun; Lu Hongwei; Lin Shiyao; Zhong Guoqiang; Xu Ping; Zhang Jizong

2011-01-01

For suppressing the energy of runaway electrons in tokamak plasma, we analyzed the X-ray energy spectra by runaway electrons in different discharges of the HT-7 tokamak experiment performed in the autumn of 2009. The resonant phenomenon between runaway electrons and magnetic ripple was found. Although, the energy of runaway electrons in the plasma core can be as high as several tens of MeV, but when they are transported to the edge, the electron energy are limited to a certain range by resonance with the magnetic ripple of different harmonic numbers. The runaway electrons under high loop voltage resonate with low step magnetic perturbations, with high energy gain; whereas the runaway electrons under low loop voltage resonate with high level magnetic perturbations, with low energy gain. Using this mechanism, the energy of runaway electrons can be restricted to a low level, and this will significantly mitigate the damage effect on the equipment caused by runaway electrons. (authors)

ICRF experiments and synergy with LHCD on HT-6M tokamak

International Nuclear Information System (INIS)

Li, J.; Yin, F.X.; Wan, B.N.

1997-01-01

The successful ion cyclotron heating (ICRH) experiment with high power density of nearly 1MW/m 3 was carried out in HT-6M tokamak. The good heating efficiency was achieved by using different wall conditioning techniques, such as He GDC, Ti gettering and boronization. With 300kW injected RF power, the ion temperature reach about 750eV and Te increases from 700eV to about 1keV. Synergy effects between lower hybrid current drive (LHCD) and ICRH have some unique features. The current driven efficiency improved in full current drive case from 0.8x10 19 AW -1 M -2 (without ICRH) to 1.75x10 19 AW -1 M -2 (with ICRH). The reason for this high current driven efficiency may because the mode conversion at ion-ion hybrid resonance to an Ion Bernstein Wave (IBW) which is damped on the fast electron. (author)

Investigation on synergy of IBW and LHCD for integrated high performance operation in HT-7 tokamak

International Nuclear Information System (INIS)

Wan Baonian

2002-01-01

Control of the current density profile has been realized with off-axis current drive by LHW in the HT-7 tokamak predicted by a 2D FP code simulation and supported by measurements of a vertical HX array. IBW is explored to improve performance through heating electrons in the selected region. Strong synergy effect on driven current profile and increased driven efficiency was observed. Electron temperature shows an ITB-like profile with a significantly improved performance. Operation of IBW and LHCD synergetic discharges was optimized through moving the IBW resonant layer to maximize the plasma performance and to avoid the MHD activities. A variety of high performance discharges indicated by β N *H89=1∼ 4 was produced for several tens energy confinement times. This operation mode utilizing synergy effect of IBW and LHCD provide a new way to obtain steady-state operation in advanced tokamak scenario. (author)

Research using small tokamaks

International Nuclear Information System (INIS)

1991-01-01

The technical reports contained in this collection of papers on research using small tokamaks fall into four main categories, i.e., (i) experimental work (heating, stability, plasma radial profiles, fluctuations and transport, confinement, ultra-low-q tokamaks, wall physics, a.o.), (ii) diagnostics (beam probes, laser scattering, X-ray tomography, laser interferometry, electron-cyclotron absorption and emission systems), (iii) theory (strong turbulence, effects of heating on stability, plasma beta limits, wave absorption, macrostability, low-q tokamak configurations and bootstrap currents, turbulent heating, stability of vortex flows, nonlinear islands growth, plasma-drift-induced anomalous transport, ergodic divertor design, a.o.), and (iv) new technical facilities (varistors applied to establish constant current and loop voltage in HT-6M), lower-hybrid-current-drive systems for HT-6B and HT-6M, radio-frequency systems for HT-6M ICR heating experimentation, and applications of fiber optics for visible and vacuum ultraviolet radiation detection as applied to tokamaks and reversed-field pinches. A total number of 51 papers are included in the collection. Refs, figs and tabs

Preliminary observation on coordination of pellet injection and ion Bernstein wave on a HT-7 tokamak

International Nuclear Information System (INIS)

Yang Yu; Zhao Yanping; Li Jiangang; Wan Baonian; Luo Jiarong; Gu Xuemao

2002-01-01

A pellet injection (PI) experiment was performed during the application of the ion Bernstein wave on a HT-7 tokamak. A preliminary coordination effect was observed. With a lower wave power, shortly after PI, the coupling of the wave was enhanced, and the particle confinement was improved. With higher power, off-axis heating for 15% at about α/3 in the low field side was observed

Improved plasma confinement by modulated toroidal current on HT-7 superconducting tokamak

International Nuclear Information System (INIS)

Mao Jianshan; Zhao Junyu; Shen Biao; Luo Jiarong

2004-01-01

The improved confinement phase was observed during modulating toroidal current on the Hefei superconducting Tokamak-7 (HT-7). This improved plasma confinement phase is characterized by suppressing magnetohydrodynamic (MHD) instabilities effectively, thus increased the central line averaged electron density and the central electron temperature about 33%, out-put steeper density profiles, and reduced hydrogen radiation from the edge as well. The global energy confinement time was increased by 27%-45%; The impurity radiation was reduced by modulation of plasma toroidal current; particle confinement time was increased about two times; a stronger radial negative electric field formed inside the limiter. The radial electric field during modulating current was calculated and disscused. (authors)

Removal of particles by ICRF cleaning in HT-7 superconducting tokamak

International Nuclear Information System (INIS)

Hu Jiansheng; Li Jiangang; Zhang Shouyin; Gu Xuemao; Zhang Xiaodong; Zhao Yanping; Gong Xianzu; Kuang Guangli; Li Chengfu; Luo Jiarong; Wang Xiaoming; Gao Xiang; Wan Baonian; Xie Jikang; Wan Yuanxi

2001-01-01

The ICRF (Ion Cyclotron Range Frequency) cleaning technique has been used as a routine wall cleaning method in the HT-7 superconducting tokamak. In a wide range of toroidal field, the removal rate of residual gas by ICRF cleaning was about twenty times higher than that of glow discharge cleaning (GDC). At different gas pressure and RF power levels, the ICRF cleaning is studied carefully. A good impurity cleaning effect and a very high hydrogen removal rate were obtained. The removal rate of hydrogen by 5 kW ICRF cleaning achieved was 1.6 x 10 -5 Torr.l/s. And the relationships among pressure P, outgassing rate Q, atomic layers L absorbed on surface and the cleaning mode were discussed briefly

Continuous and real-time data acquisition system for superconducting tokamaks HT-7 and TRIAM-1M

International Nuclear Information System (INIS)

Wang, F.; Luo, J.R.; Nakamura, K.; Sato, K.N.; Hanada, K.; Sakamoto, M.; Idei, H.; Kawasaki, S.; Nakashima, H.

2006-01-01

Conventional data acquisition systems cannot deal with data acquisition for a long-time discharge of a nuclear fusion reactor. Thus, continuous data acquisition with a real-time data presentation during discharge must be developed. Two data acquisition systems, which include alternating CAMAC data acquisition and long-time PCI data acquisition, are designed for the long-time operation of HT-7 tokamak. Since an effective alternating mode is adopted, the alternating CAMAC data acquisition can accurately and continuously acquire data at a rate of 10 kHz. The acquired data is immediately transmitted to a data server and real-time results can be presented during the plasma discharge. As for the long-time PCI data acquisition, a special kind of PCI A/D card, which has a hard disk on board, is designed to collect data at a max speed of 200 kHz. Thus, the total sampling duration is only related to the capacity of the hard disk on board. These two types of data acquisitions were applied to HT-7 tokamak and a 250 s discharge was acquired. These data acquisition systems were also successfully demonstrated on a 2500 s plasma discharge on TRIAM-1M. This paper describes the two data acquisitions in detail

Study of LHW and IBW synergy experiment on the HT-7 superconducting tokamak

International Nuclear Information System (INIS)

Gao, X.

2001-01-01

A successful experiment on lower hybrid wave (LHW) and ion Bernstein wave (IBW) synergy has been carried out in the HT-7 superconducting tokamak. With 500 kW of LHW heating power and 200 kW of injected IBW power, it is observed that the ion temperature increases from 500 eV to about 850 eV, the electron temperature increases from 800 eV to 1.2 keV, and the averaged electron density increases from 0.9x10 19 m -3 to 2.6x10 19 m -3 . The plasma parameters were obviously enhanced by means of the LHW and IBW heating and their synergy. The charge-exchange spectra of the neutral particle analysis (NPA) diagnostics data clearly showed that the high-energy ion tail which was produced by the LHW was decreased by the synergy with the IBW, and the bulk ion temperature was increased. The mechanism of the LHW and IBW synergy effect is discussed. (author)

Lower hybrid current drive experiments with graphite limiters in the HT-7 superconducting tokamak

International Nuclear Information System (INIS)

Liu, J.; Gao, X.; Hu, L.Q.; Asif, M.; Chen, Z.Y.; Ding, B.J.; Zhou, Q.; Liu, H.Q.; Jie, Y.X.; Kong, W.; Lin, S.Y.; Ding, Y.H.; Gao, L.; Xu, Q.

2006-01-01

Recent progress of lower hybrid (LH) experiments with new graphite limiters configuration in the HT-7 tokamak is presented. The lower hybrid current drive (LHCD) efficiency can be determined by fitting based on experimental data. Improved particle confinement was observed via LHCD (P LHW >300 kW) characterized by the particle confinement time τ p increased about 1.56 times. It is found that runaways are suppressed during loop voltage is decreasing at the flat-top phase of LH discharges. The main limitations of pulse length are presented in long-pulse experiments with new limiter configuration

Enhanced lower hybrid current drive experiments on HT-7 tokamak

International Nuclear Information System (INIS)

Shen Weici; Kuang Guangli; Liu Yuexiu; Ding Bojiang; Shi Yaojiang

2003-01-01

Effective Lower Hybrid Current Driving (LHCD) and improved confinement experiments in higher plasma parameters (I p >200 kA, n e >2 x 10 13 cm -3 , T e ≥1 keV) have been curried out in optimized LH wave spectrum and plasma parameters in HT-7 superconducting tokamak. The dependence of current driving efficiency on LH power spectrum, plasma density (anti n e ) and toroidal magnetic field B T has been obtained under optimal conditions. A good CD efficiency was obtained at higher plasma current and higher electron density. The improvement of the energy confinement time is accompanied with the increase in line averaged electron density, and in ion and electron temperatures. The highest current driving efficiency reached η CD =I p (anti n e )R/P RF ≅1.05 x 10 19 Am -2 /W. Wave-plasma coupling was sustained in a good state and the reflective coefficient was less than 5%. The experiments have also demonstrated the ability of LH wave in the start-up and ramp-up of the plasma current. The measurement of the temporal distribution of plasma parameter shows that lower hybrid leads to a broader profile in plasma parameter. The LH power deposition profile and the plasma current density profile were modeled with a 2D Fokker-Planck code corresponding to the evolution process of the hard x-ray detector array

Modification of boundary fluctuations by LHCD in the HT-7 tokamak

International Nuclear Information System (INIS)

Song Mei; Wan Baonian; Xu Guosheng; Ling Bili

2003-01-01

Measurements of boundary fluctuations and fluctuation driven electron fluxes have been performed in ohmic and lower hybrid current drive enhanced confinement plasma using a graphite Langmuir probe array on HT-7 tokamak. The fluctuations are significantly suppressed and the turbulent fluxes are remarkably depressed in the enhanced plasma. We characterized the statistical properties of fluctuations and the particle flux and found a non-Gaussian character in the whole scrape-off layer with minimum deviations from Gaussian in the proximity of the velocity shear layer in ohmic plasma. In the enhanced plasma the deviations in the boundary region are all reduces obviously. The fluctuations and induced electron fluxes show sporadic bursts asymmetric in time and the asymmetry is remarkably weakened in the lower hybrid current driving (LHCD) phase. The results suggest a coupling between the statistical behaviour of fluctuations and the turbulent flow

Modification of boundary plasma behavior by Ion Bernstein Wave heating on HT-7 tokamak

International Nuclear Information System (INIS)

Xu Guoshen

2002-01-01

Cooperated with Fusion Research Center, the University of Texas at Austin, U.S.A. The boundary plasma behavior during Ion Bernstein Wave (IBW) heating was investigated using Langmuir probe arrays on HT-7 tokamak. The particle confinement improvement of over a factor of 2 was observed in 30 MHz IBW heated plasma with RF power > 120 kW. The strong de-correlation effect of fluctuations resulted in that the turbulent particle flux dropped more than an order of magnitude. In IBW heated plasma, an additional inward E r and associated poloidal ExB flows were produced, which could account for the additional poloidal velocity in the electron diamagnetic direction in the scrape-of layer (SOL). Three-wave nonlinear phase coupling increased evidently and low frequency fluctuations (about 5 kHz) were generated, which dominated the boundary turbulence during IBW heating. The 5/2-D resonant layer was located in the plasma edge region, which is found to be the mechanism underlying these phenomena. (author)

Hard X-Ray PHA System on the HT-7 Tokamak

International Nuclear Information System (INIS)

Lin Shiyao; Shi Yuejiang; Wan Baonian; Chen Zhongyong; Hu Liqun

2006-01-01

A new hard X-ray pulse-height analysis (PHA) system has been established on HT-7 tokamak for long pulse steady-state operation. This PHA system consists of hard X-ray diagnostics and multi-channel analysers (MCA). The hard X-ray diagnostics consists of a vertical X-ray detector array (CdTe) and a horizontal X-ray detector array (NaI). The hard X-ray diagnostics can provide the profile of power deposition and the distribution function of fast electron during radio frequency (RF) current drive. The MCA system is the electronic part of the PHA system, which has been modularized and linked to PC through LAN. Each module of MCA can connect with 8 X-ray detectors. The embedded Ethernet adapter in the MCA module makes the data communication between PC and MCA very convenient. A computer can control several modules of MCA through certain software and a hub. The RAM in MCA can store 1024 or more spectra for each detector and therefore the PHA system can be applied in the long pulse discharge of several minutes

Recycling behaviour during long pulse discharges after ICRF boronization in the HT-7 tokamak

International Nuclear Information System (INIS)

Huang, J.; Wan, B.N.; Li, J.G.; Gong, X.Z.; Zhang, X.D.; Wu, Z.W.; Zhou, Q.

2006-01-01

The evolution of recycling behaviour has been investigated during long pulse discharges in the HT-7 tokamak after ICRF boronization (C 2 B 10 H 12 ) using the H/(H+D) ratio and the edge recycling coefficient R. After boronization, impurity reduction is observed, attributed to the fresh boron film, but the recycling coefficient can exceed unity due to a large amount of hydrogen absorbed in the film, leading to an uncontrollable density rise and discharge termination. When the H/(H+D) ratio was reduced to less than 25%, the electron density was easily controlled. The longest discharge, up to 240 s with central electron temperature T e (0) of about 1.0 keV and central electron density n e (0) of 0.8 x 10 19 m -3 , was achieved following boronization. After many discharges the effectiveness of boron film was weakened, and the density rise was correlated with an increase in both carbon and oxygen radiation which limited the duration of long pulse discharges

Improved confinement mode induced by the MARFE on the HT-7 superconducting tokamak

International Nuclear Information System (INIS)

Gao, X.; Zhao, Y.P.; Luo, J.R.; Jie, Y.X.; Gong, X.Z.; Wan, B.N.; Li, J.G.; Yin, F.X.; Kuang, G.L.; Zhang, X.D.; Zhang, S.Y.; Qiu, N.; Liu, X.N.; Zhao, J.Y.; Yang, Y.; Bao, Y.; Lin, B.L.; Wu, Z.W.; Li, Y.D.; Xu, Y.H.; Yang, K.; Wang, G.X.; Ye, W.W.; Chen, L.; Shi, Y.J.; Song, M.; Zhang, X.M.; Qin, P.J.; Gu, X.M.; Cui, N.Z.; Fan, H.Y.; Liu, S.X.; Chen, Y.F.; Hu, L.Q.; Hu, J.S.; Xia, C.Y.; Ruan, H.L.; Tong, X.D.; Mao, J.S.; Xie, J.K.; Wan, Y.X.

1999-01-01

In the HT-7 superconducting tokamak, the onset of a multifaceted asymmetric radiation from the edge (MARFE) usually occurs in the early ohmic discharges of each experimental campaign before wall conditioning. The occurrence and location of a MARFE is identified by different diagnostic systems. An improved confinement mode plasma which was induced by the MARFE is observed, and the global particle confinement time increases 1.9 times. The relaxation time between the MARFE event trigger and the L-H transition is about 1.4 ms, the following L-H transition time is 1.9 ms, and the improved confinement mode phase is maintained for about 40 ms. The MARFE cools the plasma edge, and the electron density profile is observed to become more narrow and peaked. The occurrence of a MARFE is strongly correlated with Z eff but not with the density, and it always occurs at Z eff = 3-8 ohmic discharges. In the case of a good wall condition (Z eff = 1-2), the onset of MARFEs has not been observed before reaching the Greenwald density limit. (author)

Design and experimental results of feedback control of Ohmic-heating transformer magnetic flux by LHCD power in HT-7 Tokamak

International Nuclear Information System (INIS)

Yiyun Huang

2006-01-01

In order to make a research on long pulse or even steady state operation with non-inductive drive in plasma discharge, a new feedback control scheme instead of the previous one has been designed and operated in HT-7 [HT-7 team presented by J. Li, et al., Plasma Phys. Control. Fusion 42 (2) (2000) 135-146] Tokamak experiment, 2004. Consumption of iron-core transformer magnetic flux (MFT) is feedback controlled for the first time by power of lower hybrid current drive (LHCD) P LH , when the Ohmic-heating circuit current can maintain the plasma current I P constant with another feedback control loop, which make MFT evolve at alternating-change state to avoid flux saturation. Plasma current I P can be maintained steadily up to 120s in this operation mode at reduced plasma parameters (I P ∼50-100KA, average density n-bar e =0.4-0.5x10 19 m -3 , P LH =100-200KW). Design and experimental results are presented in the paper, which including control model analysis, configurations of control system and MFT feedback control experiments in HT-7. The high voltage power supply (HVPS) of LHCD is the main controller that regulates the LHCD power into the plasma to control the MFT

Design and simulation for the pulse high-voltage DC power supply (HVPS) of 1.2 MW/2.45 GHz HT-7U lower hybrid current drive system

International Nuclear Information System (INIS)

Huang Yiyun; Kuang Guangli; Xu Weihua; Liu Baohua; Lin Jianan; Wu Junshuan; Zheng Guanghua; Yang Chunshen

2000-01-01

The superconducting tokamak HT-7U has been designed by the Institute of Plasma Physics since 1998 and will be set up before 2003. The 1.2 MW/2.45 GHz HT-7U LHCD (Lower hybrid current drive) system which being the most efficient non-induction device can heat the plasma and drive the plasma current has been efficiently in operation now, and a particular design of the 2.8 MW/-35 kV high-voltage DC power supply has been already completed and will apply to the klystron of LHCD on HT-7 and the future HT-7U, and the project of the power supply has been examined and approved professionally by an authorized group of high-level specialist in the Institute of Plasma Physics. The detailed design of the power supply and the simulation results are referred

The development of joining doped graphite to copper for first wall application in HT-7 tokamak

Energy Technology Data Exchange (ETDEWEB)

Zhou Zhangjian, E-mail: zhouzhj@mater.ustb.edu.cn [School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Zhong Zhihong [School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Chen Junling [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Ge Changchun [School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083 (China)

2010-12-15

Two joining methods have been developed for joining carbon based plasma facing material to copper based heat sink material for the potential application in HT-7 and EAST tokamak. The first joining method is based on brazing technique by using a rapidly solidified foil-type Ti-Zr based amorphous filler with a melting temperature of 850 deg. C. The other joining method is direct active metal casting-casting the premixed powders of copper and active transition metals on the mechanical machined carbon surface directly. SEM observations demonstrate high quality of joining surface for both joints. The brazing technique is more promising for fabrication joint with larger size compared with the direct active alloy casting method. High heat flux test using an e-beam device was performed on the actively cooled C/Cu joint fabricated by brazing method. There has no damage occurred on the joint after heat loading at 6 MW/m{sup 2}.

Observation of magnetohydrodynamics instabilities in ion Bernstein wave and lower-hybrid-current driving synergetic discharges on HT-7 tokamak

International Nuclear Information System (INIS)

Mao Jianshan; Luo Jiarong; Shen Biao; Zhao Junyu; Hu Liqun; Zhu Yubao; Xu Guosheng; Asif, M.; Gao Xiang; Wan Baonian

2004-01-01

The normalized performance indicated by the product of β N H 89 >2 was achieved by a combination of the lower hybrid current driving (LHCD) and the ion Bernstein wave (IBW) heating in the HT-7 tokamak. More than 80% of the plasma current was sustained by the LHCD and the bootstrap current. Large edge pressure gradients were observed. The magnetohydrodynamic (MHD) instabilities were often driven to terminate the discharge or reduce the discharge performance, when the IBW resonant layer was near the rational surface. The resonant layer of the safety factor q=2 is located at 0.6 a with a=27 cm being the minor radius. The width of magnetic island (the poloidal mode number m=2) was about 2 cm. The plasma energy was reduced quickly by 30% by MHD instabilities. The behaviour of MHD instabilities is reported. A large sawtooth activity (m=1) was observed before inducing MHD (m=2)

Analysis and Performance of the Thomson Scattering Diagnostics on HT-7 Tokamak Based on I-EMCCD

International Nuclear Information System (INIS)

Shao Chunqiang; Zhao Junyu; Zang Qing; Han Xiaofeng; Xi Xiaoqi; Yang Jianhua; Chen Hui; Hu Ailan

2014-01-01

A visible light imaging Thomson scattering (VIS-TVTS) diagnostic system has been developed for the measurement of plasma electron temperature on the HT-7 tokamak. The system contains a Nd:YAG laser (λ = 532 nm, repetition rate 10 Hz, total pulse duration ≍ 10 ns, pulse energy > 1.0 J), a grating spectrometer, an image intensifier (I.I.) lens coupled with an electron multiplying CCD (EMCCD) and a data acquisition and analysis system. In this paper, the measurement capability of the system is analyzed. In addition to the performance of the system, the capability of measuring plasma electron temperature has been proved. The profile of electron temperature is presented with a spatial resolution of about 0.96 cm (seven points) near the center of the plasma

Study on the characters of high voltage charging power supply system for diagnostics neutral beam on HT-7 Tokamak

International Nuclear Information System (INIS)

Zhang Jian; Huang Yiyun; Liu Baohua; Guo Wenjun; Shen Xiaoling; Wei Wei

2011-01-01

A high voltage power supply system has been developed for the diagnostic neutral beam on the HT-7 experimental Tokamak, and the over-voltage phenomenon of storage capacitor was founded in the experiment. In order to analyse and resolve this problem, the structure and principle of high voltage power supply is described and the primary high voltage charging power supply system is introduced in detail. The phenomenon of over-voltage on the capacitors is also studied with circuit model, and the conclusion is obtained that the leakage inductance is the mA in reason which causes the over-voltage on the capacitors. (authors)

Towards steady-state operational design for the data and PF control systems of the HT-7U

International Nuclear Information System (INIS)

Luo, J.R.; Zhu, L.; Wang, H.Z.; Ji, Z.S.; Wang, F.

2003-01-01

Fusion energy is an ultimate and inexhaustible source of energy for mankind and is expected to be obtained in controlled operation within this century. Among various possible candidates for fusion, the tokamak is presently the most qualified one, and since it uses superconducting magnetic coils, it will be adequate for steady-state operation. The HT-7U superconducting tokamak is a part of national project in China on fusion research, scheduled to become available on-line by the end of 2004 (Wan Y.X. and HT-7 and HT-7U Groups 2000 Overview of steady state operation of HT-7 and present status of the HT-7U project Nucl. Fusion 40 1057). The control system of the HT-7U is designed as a distributed control system (HT7UDCS), including many subsystems that provide the various functions of supervision, remote control, real-time monitoring, data acquisition and data handling. The major features of the HT-7U tokamak, which make long-pulse (∼1000 s) operation possible are the flexible poloidal field (PF) system, an auxiliary heating system, the current-driving system and a divertor system. In order to realize these features simultaneously, real-time data handling and analysis, along with a significant control capability is required. This paper discusses the design of the HT7UDCS. (author)

Pellet injection experiments on tokamaks in ASIPP, China

International Nuclear Information System (INIS)

Yang, Y.; Bao, Y.; Li, J.; Gu, X.; He, Y.

1999-01-01

Pellet Injection has been proven to be an effective method for deep fuelling of fusion devices. Improvements of both the particle confinement and the energy confinement were observed in many experiments. In HT-6M and HT-7 tokamaks, single and multi-pellet experiments are tried, and attractive results are obtained

Plasma recovery after various events in HT-7 superconducting tokamak

International Nuclear Information System (INIS)

Hu, J.S.; Li, J.G.

2008-01-01

Normal plasma recoveries after various events, such as after shutdown, various boronization, oxidation and large air leak, were investigated in the 2007 campaign of HT-7. Plasma recoveries, including disruptive plasmas, would depend on the wall status, such as impurities content and hydrogen retention. After shutdown or air leak, impurities made plasma recovery very difficult. After boronization, plasma recoveries would depend on the procedures of the boronization (C 2 B 10 H 12 ). After oxidation, boronization would effectively suppress impurities and would be beneficial for plasma recovery. ICRF cleanings in various working gases, such as He and D 2 , would be useful for impurities and hydrogen removal. This research is important for effective operation of HT-7 and would be useful for EAST and ITER operations.

Pellet injection experiments on tokamaks in ASIPP, China

International Nuclear Information System (INIS)

Yang, Y.; Bao, Y.; Li, J.; Gu, X.; He, Y.

2001-01-01

Pellet injection has been proved to be an effective method for deep fueling of fusion devices. Improvements of both the particle confinement and the energy confinement were observed in many experiments. In HT-6M and HT-7 tokamaks, single and multi-pellet experiments are tried, and attractive results are obtained. (author)

Design of a long pulse and low drift analog integrator in HT-7

International Nuclear Information System (INIS)

Liu Dongmei; Wan Baonian; Shen Biao

2007-01-01

Magnetic measurements are a fundamental diagnostic system for Tokamak. Inductive magnetic coils are used on HT-7. So the integrator is required to determine the magnetic field strength. This paper discusses the traditional analog integrator, and introduces a new integrator based on real-time drift compensation schemes. This new design can significantly reduce the integral error caused by input offset, temperature-induced drift, noise and so on. Operation in the HT-7 Tokamak shows that very low drift and noise characteristics compatible of the now integrators can meet requirement of long pulse discharges. (authors)

Genotype-Dependent Difference in 5-HT2C Receptor-Induced Hypolocomotion: Comparison with 5-HT2A Receptor Functional Activity

Directory of Open Access Journals (Sweden)

Darya V. Bazovkina

2015-01-01

Full Text Available In the present study behavioral effects of the 5-HT2C serotonin receptor were investigated in different mouse strains. The 5-HT2C receptor agonist MK-212 applied intraperitoneally induced significant dose-dependent reduction of distance traveled in the open field test in CBA/Lac mice. This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221. To study the role of genotype in 5-HT2C receptor-induced hypolocomotion, locomotor activity of seven inbred mouse strains was measured after MK-212 acute treatment. We found that the 5-HT2C receptor stimulation by MK-212 decreased distance traveled in the open field test in CBA/Lac, C57Bl/6, C3H/He, and ICR mice, whereas it failed to affect locomotor activity in DBA/2J, Asn, and Balb/c mice. We also compared the interstrain differences in functional response to 5-HT2C and 5-HT2A receptors activation measured by the quantification of receptor-mediated head-twitches. These experiments revealed significant positive correlation between 5-HT2C and 5-HT2A receptors functional responses for all investigated mouse strains. Moreover, we found that 5-HT2A receptor activation with DOI did not change locomotor activity in CBA/Lac mice. Taken together, our data indicate the implication of 5-HT2C receptors in regulation of locomotor activity and suggest the shared mechanism for functional responses mediated by 5-HT2C and 5-HT2A receptors.

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

Directory of Open Access Journals (Sweden)

Malgorzata S. Martin-Gronert

2016-04-01

Full Text Available Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC peptides within the arcuate nucleus of the hypothalamus (ARC. We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus of in utero growth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist.

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats.

Science.gov (United States)

Martin-Gronert, Malgorzata S; Stocker, Claire J; Wargent, Edward T; Cripps, Roselle L; Garfield, Alastair S; Jovanovic, Zorica; D'Agostino, Giuseppe; Yeo, Giles S H; Cawthorne, Michael A; Arch, Jonathan R S; Heisler, Lora K; Ozanne, Susan E

2016-04-01

Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus ofin uterogrowth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist. © 2016. Published by The Company of Biologists Ltd.

Generation of sheared poloidal flows by electrostatic and magnetic Reynolds stress in the boundary plasma of HT-7 tokamak

International Nuclear Information System (INIS)

Xu, G.S.; Wan, B.N.; Li, J.

2005-01-01

The radial profiles of electrostatic and magnetic Reynolds stress (Maxwell stress) have been measured in the plasma boundary region of HT-7 tokamak. Experimental results show that the radial gradient of electrostatic Reynolds stress (ERS) changes sign across the last closed flux surface, and the neoclassical flow damping and the damping due to charge exchange processes are balanced by the radial gradient of ERS, which sustains the equilibrium sheared flow structure in a steady state. The contribution of magnetic Reynolds stress was found unimportant in a low β plasma. Detailed analyses indicate that the propagation properties of turbulence in radial and poloidal directions and the profiles of potential fluctuation level are responsible for the radial structure of ERS. (author)

A novel fast-scanning microwave heterodyne radiometer system for electron cyclotron emission measurements in the HT-7 superconducting tokamak

International Nuclear Information System (INIS)

Zhang, S.Y.; Wan, Y.X.; Xie, J.K.; Luo, J.R.; Li, J.G.; Kuang, G.L.; Gao, X.; Zhang, X.D.; Wan, B.N.; Wang, K.J.; Mao, J.S.; Gong, X.Z.; Qin, P.J.

2000-01-01

Two sets of fast-scanning microwave heterodyne radiometer receiver systems employing backward-wave oscillators in the 78-118 GHz and 118-178 GHz ranges were developed for electron cyclotron emission measurements (ECE) on the HT-7 superconducting tokamak. The double-sideband radiometer in the 78-118 GHz range measures 16 ECE frequency points with a scanning period of 0.65 ms. The novel design of the 2 mm fast-scanning heterodyne radiometer in the 118-178 GHz range enables the unique system to measure 48 ECE frequency points in 0.65 ms periodically. The plasma profile consistency in reproducible ohmic plasmas was used to relatively calibrate each channel by changing the toroidal magnetic field shot-by-shot. The absolute temperature value was obtained by a comparison with the results from the soft x-ray pulse height analysis measurements and Thomson scattering system. A preliminary temperature profile measurement result in pellet injection plasma is presented. (author)

Steady state operation of tokamaks. Proceedings of a technical committee meeting

International Nuclear Information System (INIS)

2000-10-01

The first IAEA Technical Committee Meeting (TCM) on Steady State Operation of Tokamaks was organized to discuss the operations of present long-pulse tokamaks (TRIAM-1M, TORE SUPRA, MT-7, HT-7M, HL-1M) and the plans for future steady-state tokamaks such as SST-1, CIEL, and HT-7U. This meeting, held from 13-15 October 1998, was hosted by the Academia Sinica Institute of Plasma Physics (ASIPP), Hefei, China. Participants from China, France, India, Japan, the Russian Federation, and the IAEA participated in the meeting. There were 18 individual presentations plus general discussions on many topics, including superconducting magnet systems, cryogenics, plasma position control, non-inductive current drive, auxiliary heating, plasma-wall interactions, high heat flux components, particle control, and data acquisition

Electron temperature fluctuation in the HT-7 tokamak plasma observed by electron cyclotron emission imaging

International Nuclear Information System (INIS)

Xiao-Yuan, Xu; Jun, Wang; Yi, Yu; Yi-Zhi, Wen; Chang-Xuan, Yu; Wan-Dong, Liu; Bao-Nian, Wan; Xiang, Gao; Luhmann, N. C.; Domier, C. W.; Wang, Jian; Xia, Z. G.; Shen, Zuowei

2009-01-01

The fluctuation of the electron temperature has been measured by using the electron cyclotron emission imaging in the Hefei Tokamak-7 (HT-7) plasma. The electron temperature fluctuation with a broadband spectrum shows that it propagates in the electron diamagnetic drift direction, and the mean poloidal wave-number k-bar θ is calculated to be about 1.58 cm −1 , or k-bar θρ s thickapprox 0.34. It indicates that the fluctuation should come from the electron drift wave turbulence. The linear global scaling of the electron temperature fluctuation with the gradient of electron temperature is consistent with the mixing length scale qualitatively. Evolution of spectrum of the fluctuation during the sawtooth oscillation phases is investigated, and the fluctuation is found to increase with the gradient of electron temperature increasing during most phases of the sawtooth oscillation. The results indicate that the electron temperature gradient is probably the driver of the fluctuation enhancement. The steady heat flux driven by electron temperature fluctuation is estimated and compared with the results from power balance estimation. (fluids, plasmas and electric discharges)

Numerical simulation and analysis for the baking out system of the HT-7U super-conducting tokamak device

International Nuclear Information System (INIS)

Song Yuntao

2004-01-01

It can provide an ultrahigh vacuum location for the plasma operation. In order to improve its vacuum degree and attain a high quality operation environment for plasma, it is very important to proceed 250 degree C baking out to clear the wall before the plasma operation. The paper firstly gives two kinds of structures for the baking of the vacuum vessel, in which one is the baking by electricity and another is baking by the nitrogen gas. Secondly based on the numerical simulation and analysis, some results have been attained such as the baking power, temperature field distribution and thermal stress for the vacuum vessel, which can provide some valuable theory basis for the engineering design and optimization of the baking system of the HT-7U vacuum vessel or other similar super-conducting tokamak devices

Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

Science.gov (United States)

Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

2014-01-03

Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists. Copyright © 2013 Elsevier Inc. All rights reserved.

Tokamaks. 2. ed.

International Nuclear Information System (INIS)

Wesson, John; Campbell, D.J.; Connor, J.W.

1997-01-01

It is interesting to recall the state of tokamak research when the first edition of this book was written. My judgement of the level of real understanding at that time is indicated by the virtual absence of comparisons of experiment with theory in that edition. The need then was for a 'handbook' which collected in a single volume the concepts and models which form the basis of everyday tokamak research. The experimental and theoretical endeavours of the subsequent decade have left almost all of this intact, but have brought a massive development of the subject. Firstly, there are now several areas where the experimental behaviour is described in terms of accepted theory. This is particularly true of currents parallel to the magnetic field, and of the stability limitations on the plasma pressure. Next there has been the research on large tokamaks, hardly started at the writing of the first edition. Now our thinking is largely based on the results from these tokamaks and this work has led to the long awaited achievement of significant amounts of fusion power. Finally, the success of tokamak research has brought us face to face with the problems involved in designing and building a tokamak reactor. The present edition maintains the aim of providing a simple introduction to basic tokamak physics, but also includes an account of the advances outlined above. (Author)

Haliotis tuberculata hemocyanin (HtH): analysis of oligomeric stability of HtH1 and HtH2, and comparison with keyhole limpet hemocyanin KLH1 and KLH2.

Science.gov (United States)

Harris, J R; Scheffler, D; Gebauer, W; Lehnert, R; Markl, J

2000-12-01

The multimeric/higher oligomeric states of the two isoforms of Haliotis tuberculata hemocyanin (HtH1 and HtH2) have been assessed by transmission electron microscopy (TEM) of negatively stained specimens, for comparison with previously published structural data from keyhole limpet hemocyanin (KLH1 and KLH2) [see Harris, J.R., Gebauer, W., Guderian, F.U., Markl, J., 1997a. Keyhole limpet hemocyanin (KLH), I: Reassociation from Immucothel followed by separation of KLH1 and KLH2. Micron, 28, 31-41; Harris, J.R., Gebauer, W., Söhngen, S.M., Nermut, M.V., Markl, J., 1997b. Keyhole limpet hemocyanin (KLH). II: Characteristic reassociation properties of purified KLH1 and KLH2. Micron, 28, 43-56; Harris, J.R., Gebauer, W., Adrian, M., Markl, J., 1998. Keyhole limpet hemocyanin (KLH): Slow in vitro reassociation of KLH1 and KLH2 from Immucothel. Micron, 29, 329-339]. In purified samples of both HtH isoforms, the hollow cylindrical ca 8MDa didecamer predominates together with a small number of decamers, but tri- and longer multidecamers are detectable only in the HtH2. The stability of the two HtH isoforms under varying ionic conditions have been monitored, thereby enabling conditions for the production of stable decamers to be established. The ability of these decamers to reform multimers in the presence of 10 and 100mM concentrations of calcium and magnesium ions in Tris-HCl buffer (pH 7.4), and also of individual HtH1 and HtH2 subunits (produced by pH 9.6 dissociation in glycine-NaOH buffer), to reassociate in the presence of calcium and magnesium ions, has been assessed. For the HtH1 decamers, the predominant multimeric product is the didecamer at 10 and 100mM calcium and magnesium concentrations, whereas for the HtH2 decamers, large numbers of multidecamers are produced, with the reaction proceeding more completely at the higher calcium and magnesium concentration. With the HtH1 subunit, reassociation in the presence of 10 and 100mM calcium and magnesium ions yielded

Changes in 5-HT2A-mediated behavior and 5-HT2A- and 5-HT1A receptor binding and expression in conditional brain-derived neurotrophic factor knock-out mice

DEFF Research Database (Denmark)

Klein, A B; Santini, M A; Aznar, S

2010-01-01

Changes in brain-derived neurotrophic factor (BDNF) expression have been implicated in the etiology of psychiatric disorders. To investigate pathological mechanisms elicited by perturbed BDNF signaling, we examined mutant mice with central depletion of BDNF (BDNF(2L/2LCk-cre)). A severe impairment...... specific for the serotonin 2A receptor (5-HT(2A)R) in prefrontal cortex was described previously in these mice. This is of much interest, as 5-HT(2A)Rs have been linked to neuropsychiatric disorders and anxiety-related behavior. Here we further characterized the serotonin receptor alterations triggered...... was decreased in hippocampus of BDNF mutants, but unchanged in frontal cortex. Molecular analysis indicated corresponding changes in 5-HT(2A) and 5-HT(1A) mRNA expression but normal 5-HT(2C) content in these brain regions in BDNF(2L/2LCk-cre) mice. We investigated whether the reduction in frontal 5-HT(2A...

Optimization of the protective energy removal parameters for tokamak HT7-U superconducting magnets

Energy Technology Data Exchange (ETDEWEB)

Khvostenko, P.P.; Chudnovsky, A.N.; Posadsky, I.A. [RRC ' Kurchatov Inst.' , Nuclear Fusion Inst., Moscow (Russian Federation); Bi, Y.F.; Cheng, S.M.; He, Y.X. [Academia Sinica, Hefei, Anhui (China). Inst. of Plasma Physics

1998-07-01

The design of the HT-7U superconducting tokamak is in progress now. The design incorporates superconducting magnets of the toroidal field and poloidal field systems. Toroidal field system consists of 16 D-shape coils and poloidal field system consists of 12 coils. All coils will be use NbTi/Cu cable-in-conduit conductor cooled with forced-flow supercritical helium at 4.5 K, 4 Bar. Quench in the superconducting magnets is accompanied byconversion of the stored magnetic field energy into a thermal one which is spent on heating of both the coil part which made transition into a normal state and dump resistors. A non-uniform heating of the coil part results in the emergence of thermomechanical stresses which can cause its destruction. The protective removal of a current is realized to prevent the coil destruction at the emergence of the quench. In that case, the faster the current removal occurs, the less the coil heating is. On the other hand, the current removal rate should not be too high in order to avoid an electric breakdown by the excited inductive voltage. Optimization of the protective energy removal parameters both for TF and PF superconducting magnets is presented. (author)

Optimization of the protective energy removal parameters for tokamak HT7-U superconducting magnets

International Nuclear Information System (INIS)

Khvostenko, P.P.; Chudnovsky, A.N.; Posadsky, I.A.; Bi, Y.F.; Cheng, S.M.; He, Y.X.

1998-01-01

The design of the HT-7U superconducting tokamak is in progress now. The design incorporates superconducting magnets of the toroidal field and poloidal field systems. Toroidal field system consists of 16 D-shape coils and poloidal field system consists of 12 coils. All coils will be use NbTi/Cu cable-in-conduit conductor cooled with forced-flow supercritical helium at 4.5 K, 4 Bar. Quench in the superconducting magnets is accompanied by conversion of the stored magnetic field energy into a thermal one which is spent on heating of both the coil part which made transition into a normal state and dump resistors. A non-uniform heating of the coil part results in the emergence of thermomechanical stresses which can cause its destruction. The protective removal of a current is realized to prevent the coil destruction at the emergence of the quench. In that case, the faster the current removal occurs, the less the coil heating is. On the other hand, the current removal rate should not be too high in order to avoid an electric breakdown by the excited inductive voltage. Optimization of the protective energy removal parameters both for TF and PF superconducting magnets is presented. (author)

Effect of magnetic fluctuations on the confinement and dynamics of runaway electrons in the HT-7 tokamak

International Nuclear Information System (INIS)

Zhou, R.J.; Hu, L.Q.; Li, E.Z.; Xu, M.; Zhong, G.Q.; Xu, L.Q.; Lin, S.Y.

2013-01-01

Experimental results in the HT-7 tokamak indicated significant losses of runaway electrons due to magnetic fluctuations, but the loss processes did not only rely on the fluctuation amplitude. Efficient radial runaway transport required that there were no more than small regions of the plasma volume in which there was very low transport of runaways. A radial runaway diffusion coefficient of D_r ≈ 10 m"2s"-"1 was derived for the loss processes, and diffusion coefficient near the resonant magnetic surfaces and shielding factor ϒ = 0.8 were deduced. Test particle equations were used to analyze the effect of magnetic fluctuations on runaway dynamics. It was found that the maximum energy that runaways can gain is very sensitive to the value of a_s. a_s = (0.28 - 0.33) was found for the loss processes in the experiment, and maximum runaway energy could be controlled in the range of E = (4 MeV - 6 MeV) in this case. Additionally, to control the maximum runaway energy below 5 MeV, the normalized electric field needed to be under a critical value D_a = 6.8, and the amplitude normalized magnetic fluctuations b tilde needed to be at least of the order of b tilde ≈ 3 x 10"-"5. (author)

Increased hypothalamic 5-HT2A receptor gene expression and effects of pharmacologic 5-HT2A receptor inactivation in obese Ay mice

International Nuclear Information System (INIS)

Nonogaki, Katsunori; Nozue, Kana; Oka, Yoshitomo

2006-01-01

Serotonin (5-hydroxytryptamine; 5-HT) 2A receptors contribute to the effects of 5-HT on platelet aggregation and vascular smooth muscle cell proliferation, and are reportedly involved in decreases in plasma levels of adiponectin, an adipokine, in diabetic subjects. Here, we report that systemic administration of sarpogrelate, a 5-HT2A receptor antagonist, suppressed appetite and increased hypothalamic pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript, corticotropin releasing hormone, 5-HT2C, and 5-HT1B receptor gene expression. A y mice, which have ectopic expression of the agouti protein, significantly increased hypothalamic 5-HT2A receptor gene expression in association with obesity compared with wild-type mice matched for age. Systemic administration of sarpogrelate suppressed overfeeding, body weight gain, and hyperglycemia in obese A y mice, whereas it did not increase plasma adiponectin levels. These results suggest that obesity increases hypothalamic 5-HT2A receptor gene expression, and pharmacologic inactivation of 5-HT2A receptors inhibits overfeeding and obesity in A y mice, but did not increase plasma adiponectin levels

Implication of 5-HT(2B) receptors in the serotonin syndrome.

Science.gov (United States)

Diaz, Silvina Laura; Maroteaux, Luc

2011-09-01

The serotonin (5-HT) syndrome occurs in humans after antidepressant overdose or combination of drugs inducing a massive increase in extracellular 5-HT. Several 5-HT receptors are known to participate in this syndrome in humans and animal models. The 5-HT(2B) receptor has been proposed as a positive modulator of serotonergic activity, but whether it is involved in 5-HT syndrome has not yet been studied. We analyzed here, a putative role of 5-HT(2B) receptors in this disorder by forced swimming test (FST) and behavioral assessment in the open field. In FST, genetic (5-HT(2B)(-/-) mice) or pharmacological (antagonist RS127445 at 0.5 mg/kg) ablation of 5-HT(2B) receptors facilitated selective 5-HT reuptake inhibitors (SSRI)-induced increase of immobility time as well as expression of other symptoms related to 5-HT syndrome like hind limb abduction and Straub tail. Increase in immobility was also developed in FST by both wild type (WT) and 5-HT(2B)(-/-) mice after the administration of 5-HT(1A), 5-HT(2A) or 5-HT(2C) receptor agonists, 8-OH-DPAT (5 mg/kg), DOI (1 mg/kg), or WAY161503 (5 mg/kg), respectively. In contrast, the 5-HT(2B) receptor agonist BW723C86 (3 mg/kg) or 5-HT(1B) receptor agonist CGS12066A (2 mg/kg) decreased immobility time in both genotypes. The 5-HT syndrome induced by fluoxetine at high doses was blocked in WT and 5-HT(2B)(-/-) mice by administration of 5-HT(1A) and 5-HT(2C) receptor antagonists (WAY100635 0.5 mg/kg and SB242084 0.5 mg/kg) but not by the 5-HT(2A) receptor antagonist MDL100907 (1 mg/kg). By behavioral assessment, we confirmed that 5-HT(2B)(-/-) mice were more prone to develop 5-HT syndrome symptoms after administration of high dose of SSRIs or the 5-HT precursor 5-Hydroxytryptophan, 5-HTP, even if increases in 5-HT plasma levels were similar in both genotypes. This evidence suggests that the presence of 5-HT(2B) receptors hinders acute 5-HT toxicity once high levels of 5-HT are attained. Therefore, differential agonism

Modification of boundary plasma behavior by Ion Bernstein Wave heating on the HT-7 tokamak

International Nuclear Information System (INIS)

Xu, G.S.; Wan, B.N.; Song, M.; Ling, B.L.; Li, C.F.; Li, J.

2003-01-01

The boundary plasma behavior during Ion Bernstein Wave heating was investigated using Langmuir probe arrays on the HT-7 tokamak. A distinct weak turbulence regime was reproducibly observed in the 30 MHz IBW heated plasmas with RF power larger than 120 kW, which resulted in a particle confinement improvement of a factor of 2. The strong suppression and decorrelation effect of fluctuations resulted in the turbulent particle flux dropping by more than an order of magnitude in the plasma boundary region. An additional inward radial electric field and associated poloidal ExB flows were produced, which could account for the additional poloidal velocity in the electron diamagnetic direction at some radial locations of the boundary plasma. The electrostatic fluctuations were nearly completely decorrelated in the high frequency region and only low frequency fluctuations remained. The poloidal correlation was considerably reduced in the high poloidal wave number region and only the fluctuations with long poloidal wavelength remained. Three-wave nonlinear phase coupling between the whole frequency domain and the very low frequency region increased significantly in both the plasma edge and the SOL. Quite low frequency fluctuations (about 5 kHz) were generated, which dominated the boundary turbulence during IBW heating. Detailed analyses suggested that, when an IBW with a frequency of 30 MHz was launched into a plasma with the toroidal magnetic field between 1.75 T and 2.0 T, the ion cyclotron resonant layer of 5/2.D was located in the plasma edge region. The poloidal ExB sheared flows generated by IBW near this layer due to a ponderomotive interaction were found to be the mechanism underlying these phenomena. (author)

The effects of manipulation of presynaptic 5-HT nerve terminals of postsynaptic 5-HT1 and 5-HT2 binding sites of the rat brain

International Nuclear Information System (INIS)

Hall, H.; Wedel, I.

1985-01-01

The effects of long-term treatment of rats with alaproclate and amiflamine on the number and kinetics of 5-HT 1 and 5-HT 2 binding sites were investigated using in vitro receptor binding techniques. Some other studies have reported down-regulatory effects of alaproclate and amiflamine on 5-HT 2 binding sites in certain regions of the rat forebrain, but no such effects could be detected in the present study. Induction of a high-affinity binding site for 3 H-5-HT after long-term antidepressant treatment, as has been reported elsewhere, was not obtained in the present study. The results are compared to the effects obtained by treatment of rats with para-chloroamphetamine (PCA), which depletes the presynaptic neurons of monoamines. These different types of treatment do not cause any change in the binding properties of the specific 5-HT binding sites. It is thus concluded that such manipulations of the presynaptic 5-HT neurons do not affect the postsynaptic 5-HT 1 and 5-HT 2 binding sites. (Author)

Acetylation/deacetylation reactions of T-2, acetyl T-2, HT-2, and acetyl HT-2 toxins in bovine rumen fluid in vitro

International Nuclear Information System (INIS)

Munger, C.E.; Ivie, G.W.; Christopher, R.J.; Hammock, B.D.; Phillips, T.D.

1987-01-01

A tritiated preparation of the trichothecene mycotoxin, T-2 toxin, underwent both acetylation and deacetylation reactions when incubated with bovine rumen fluid in vitro. Products from incubations of T-2 in rumen fluid included acetyl T-2, HT-2, and acetyl HT-2. Direct studies with tritiated samples of each of these metabolites confirmed their relatively facile interconversion in the rumen. Studies with [ 3 H]HT-2 under conditions of inhibited esterase activity (added diisopropyl fluorophosphate) showed that acetylation is preferred at C-3 vs. C-4. Studies with [ 3 H]acetyl T-2 indicated that deacetylation similarly occurs with greater rapidity at C-3. There were no indications that ester hydrolysis of these trichothecenes occurred at C-8 or C-15 or that they were subjected to epoxide reduction reactions. These data suggest that acetylation of T-2 and other trichothecenes in the rumen in situ may ultimately result in the absorption of more lipophilic metabolites whose toxicological and residual properties are at present unknown

Enhancement of cortical extracellular 5-HT by 5-HT1A and 5-HT2C receptor blockade restores the antidepressant-like effect of citalopram in non-responder mice.

Science.gov (United States)

Calcagno, Eleonora; Guzzetti, Sara; Canetta, Alessandro; Fracasso, Claudia; Caccia, Silvio; Cervo, Luigi; Invernizzi, Roberto W

2009-07-01

We recently found that the response of DBA/2 mice to SSRIs in the forced swim test (FST) was impaired and they also had a smaller basal and citalopram-stimulated increase in brain extracellular serotonin (5-HT) than 'responder' strains. We employed intracerebral microdialysis, FST and selective antagonists of 5-HT1A and 5-HT2C receptors to investigate whether enhancing the increase in extracellular 5-HT reinstated the anti-immobility effect of citalopram in the FST. WAY 100635 (0.3 mg/kg s.c.) or SB 242084 (1 mg/kg s.c.), respectively a selective 5-HT1A and 5-HT2C receptor antagonist, raised the effect of citalopram (5 mg/kg) on extracellular 5-HT in the medial prefrontal cortex of DBA/2N mice (citalopram alone 5.2+/-0.3 fmol/20 microl, WAY 100635+citalopram 9.9+/-2.1 fmol/20 microl, SB 242084+ citalopram 7.6+/-1.0 fmol/20 microl) to the level reached in 'responder' mice given citalopram alone. The 5-HT receptor antagonists had no effect on the citalopram-induced increase in extracellular 5-HT in the dorsal hippocampus. The combination of citalopram with WAY 100635 or SB 242084 significantly reduced immobility time in DBA/2N mice that otherwise did not respond to either drug singly. Brain levels of citalopram in mice given citalopram alone or with 5-HT antagonists did not significantly differ. The results confirm that impaired 5-HT transmission accounts for the lack of effect of citalopram in the FST and suggest that enhancing the effect of SSRIs on extracellular 5-HT, through selective blockade of 5-HT1A and 5-HT2C receptors, could be a useful strategy to restore the response in treatment-resistant depression.

Acetylation/deacetylation reactions of T-2, acetyl T-2, HT-2, and acetyl HT-2 toxins in bovine rumen fluid in vitro

Energy Technology Data Exchange (ETDEWEB)

Munger, C.E.; Ivie, G.W.; Christopher, R.J.; Hammock, B.D.; Phillips, T.D.

A tritiated preparation of the trichothecene mycotoxin, T-2 toxin, underwent both acetylation and deacetylation reactions when incubated with bovine rumen fluid in vitro. Products from incubations of T-2 in rumen fluid included acetyl T-2, HT-2, and acetyl HT-2. Direct studies with tritiated samples of each of these metabolites confirmed their relatively facile interconversion in the rumen. Studies with (/sup 3/H)HT-2 under conditions of inhibited esterase activity (added diisopropyl fluorophosphate) showed that acetylation is preferred at C-3 vs. C-4. Studies with (/sup 3/H)acetyl T-2 indicated that deacetylation similarly occurs with greater rapidity at C-3. There were no indications that ester hydrolysis of these trichothecenes occurred at C-8 or C-15 or that they were subjected to epoxide reduction reactions. These data suggest that acetylation of T-2 and other trichothecenes in the rumen in situ may ultimately result in the absorption of more lipophilic metabolites whose toxicological and residual properties are at present unknown.

Insulating process for HT-7U central solenoid model coils

International Nuclear Information System (INIS)

Cui Yimin; Pan Wanjiang; Wu Songtao; Wan Yuanxi

2003-01-01

The HT-7U superconducting Tokamak is a whole superconducting magnetically confined fusion device. The insulating system of its central solenoid coils is critical to its properties. In this paper the forming of the insulating system and the vacuum-pressure-impregnating (VPI) are introduced, and the whole insulating process is verified under the super-conducting experiment condition

A novel approach to linearization of the electromagnetic parameters of tokamaks with an iron core

Energy Technology Data Exchange (ETDEWEB)

Fu, P. E-mail: fupeng@mail.ipp.ac.cn; Liu, Z.Z.; Zou, J.H

2002-05-01

The equivalent model of an iron core tokamak is developed, in which the electromagnetic parameters of several pairs of coils in opposite series (PCOS) are not dependent on the saturation of the iron core during tokamak operation. With this the electromagnetic parameters of all the coils in an iron core tokamak can be linearized, As an example, the electromagnetic parameters of Hefei Super-conductive Tokamak with iron core (HT-7) are linearized, and it is in good agreement with the experimental results. The linearization approach can be applied in real time plasma control and electromagnetic analysis.

Diagnostics of internal inductance in HT-7

International Nuclear Information System (INIS)

Zeng Li; Wan Baonian; Qian Jinping; Fan Hengyu

2001-01-01

Two arrays of Mirnov coils and a pair of concentric loops have been installed to superconducting tokamak HT-7. Software compensation and digital Fourier series expansion are the two techniques that have been applied successfully in measuring diamagnetic flux of concentric loops and internal inductance. The internal inductance of plasma l i , poloidal beta β p , Grad Shafranov parameter Λ, plasma minor radius α p and the center of the outermost magnetic flux surface Δ g are determined

Generation of runaway electrons during deterioration of lower hybrid power coupling in lower hybrid current drive plasmas in the HT-7 tokamak

International Nuclear Information System (INIS)

Chen, Z Y; Ju, H J; Zhu, J X; Li, M; Cai, W D; Liang, H F; Wan, B N; Shi, Y J; Xu, H D

2009-01-01

Efficient coupling of lower hybrid (LH) power from the wave launcher to the plasma is a very important issue in lower hybrid current drive (LHCD) experiments. The large unbalanced reflections in the grill trigger the LH protection system, which will trip the power, resulting in the reduction of the coupled LH power. The generation of runaway electrons has been investigated in LHCD plasmas with deterioration of LH coupling in the HT-7 tokamak. The deterioration of LH coupling results in an increase of the loop voltage and a more energetic fast electron population. These two effects favor the generation of a runaway population. It is found that most of the fast electrons generated by LH waves through parallel electron Landau damping were converted into a runaway population through the acceleration from the toroidal electric field when significant deterioration of LH coupling occurs.

BDNF downregulates 5-HT(2A) receptor protein levels in hippocampal cultures

DEFF Research Database (Denmark)

Trajkovska, V; Santini, M A; Marcussen, Anders Bue

2009-01-01

Both brain-derived neurotrophic factor (BDNF) and the serotonin receptor 2A (5-HT(2A)) have been related to depression pathology. Specific 5-HT(2A) receptor changes seen in BDNF conditional mutant mice suggest that BDNF regulates the 5-HT(2A) receptor level. Here we show a direct effect of BDNF...... on 5-HT(2A) receptor protein levels in primary hippocampal neuronal and mature hippocampal organotypic cultures exposed to different BDNF concentrations for either 1, 3, 5 or 7 days. In vivo effects of BDNF on hippocampal 5-HT(2A) receptor levels were further corroborated in (BDNF +/-) mice...... with reduced BDNF levels. In primary neuronal cultures, 7 days exposure to 25 and 50ng/mL BDNF resulted in downregulation of 5-HT(2A), but not of 5-HT(1A), receptor protein levels. The BDNF-associated downregulation of 5-HT(2A) receptor levels was also observed in mature hippocampal organotypic cultures...

Molecular and pharmacological characterization of serotonin 5-HT2α and 5-HT7 receptors in the salivary glands of the blowfly Calliphora vicina.

Science.gov (United States)

Röser, Claudia; Jordan, Nadine; Balfanz, Sabine; Baumann, Arnd; Walz, Bernd; Baumann, Otto; Blenau, Wolfgang

2012-01-01

Secretion in blowfly (Calliphora vicina) salivary glands is stimulated by the biogenic amine serotonin (5-hydroxytryptamine, 5-HT), which activates both inositol 1,4,5-trisphosphate (InsP(3))/Ca(2+) and cyclic adenosine 3',5'-monophosphate (cAMP) signalling pathways in the secretory cells. In order to characterize the signal-inducing 5-HT receptors, we cloned two cDNAs (Cv5-ht2α, Cv5-ht7) that share high similarity with mammalian 5-HT(2) and 5-HT(7) receptor genes, respectively. RT-PCR demonstrated that both receptors are expressed in the salivary glands and brain. Stimulation of Cv5-ht2α-transfected mammalian cells with 5-HT elevates cytosolic [Ca(2+)] in a dose-dependent manner (EC(50) = 24 nM). In Cv5-ht7-transfected cells, 5-HT produces a dose-dependent increase in [cAMP](i) (EC(50) = 4 nM). We studied the pharmacological profile for both receptors. Substances that appear to act as specific ligands of either Cv5-HT(2α) or Cv5-HT(7) in the heterologous expression system were also tested in intact blowfly salivary gland preparations. We observed that 5-methoxytryptamine (100 nM) activates only the Cv5-HT(2α) receptor, 5-carboxamidotryptamine (300 nM) activates only the Cv5-HT(7) receptor, and clozapine (1 µM) antagonizes the effects of 5-HT via Cv5-HT(7) in blowfly salivary glands, providing means for the selective activation of each of the two 5-HT receptor subtypes. This study represents the first comprehensive molecular and pharmacological characterization of two 5-HT receptors in the blowfly and permits the analysis of the physiological role of these receptors, even when co-expressed in cells, and of the modes of interaction between the Ca(2+)- and cAMP-signalling cascades.

Molecular and pharmacological characterization of serotonin 5-HT2α and 5-HT7 receptors in the salivary glands of the blowfly Calliphora vicina.

Directory of Open Access Journals (Sweden)

Claudia Röser

Full Text Available Secretion in blowfly (Calliphora vicina salivary glands is stimulated by the biogenic amine serotonin (5-hydroxytryptamine, 5-HT, which activates both inositol 1,4,5-trisphosphate (InsP(3/Ca(2+ and cyclic adenosine 3',5'-monophosphate (cAMP signalling pathways in the secretory cells. In order to characterize the signal-inducing 5-HT receptors, we cloned two cDNAs (Cv5-ht2α, Cv5-ht7 that share high similarity with mammalian 5-HT(2 and 5-HT(7 receptor genes, respectively. RT-PCR demonstrated that both receptors are expressed in the salivary glands and brain. Stimulation of Cv5-ht2α-transfected mammalian cells with 5-HT elevates cytosolic [Ca(2+] in a dose-dependent manner (EC(50 = 24 nM. In Cv5-ht7-transfected cells, 5-HT produces a dose-dependent increase in [cAMP](i (EC(50 = 4 nM. We studied the pharmacological profile for both receptors. Substances that appear to act as specific ligands of either Cv5-HT(2α or Cv5-HT(7 in the heterologous expression system were also tested in intact blowfly salivary gland preparations. We observed that 5-methoxytryptamine (100 nM activates only the Cv5-HT(2α receptor, 5-carboxamidotryptamine (300 nM activates only the Cv5-HT(7 receptor, and clozapine (1 µM antagonizes the effects of 5-HT via Cv5-HT(7 in blowfly salivary glands, providing means for the selective activation of each of the two 5-HT receptor subtypes. This study represents the first comprehensive molecular and pharmacological characterization of two 5-HT receptors in the blowfly and permits the analysis of the physiological role of these receptors, even when co-expressed in cells, and of the modes of interaction between the Ca(2+- and cAMP-signalling cascades.

4-[125I]iodo-(2,5-dimethoxy)phenylisopropylamine and [3H]ketanserin labeling of 5-hydroxytryptamine2 (5HT2) receptors in mammalian cells transfected with a rat 5HT2 cDNA: Evidence for multiple states and not multiple 5HT2 receptor subtypes

International Nuclear Information System (INIS)

Teitler, M.; Leonhardt, S.; Weisberg, E.L.; Hoffman, B.J.

1990-01-01

Evidence has accumulated indicating that the radioactive hallucinogens 4-bromo-[3H](2,5-dimethoxy)phenylisopropylamine ([3H]DOB) and 4-[125I]iodo-(2,5-dimethoxy)phenylisopropylamine ([125I]DOI) label an agonist high affinity state of the 5-hydroxytryptamine2 (5HT2) receptor and [3H]ketanserin labels both agonist high and low affinity states. Recently, an alternative hypothesis has been put forward proposing that the radioactive hallucinogens are labeling a 5HT2 receptor subtype distinct from the receptor labeled by [3H]ketanserin. In order to provide definitive evidence as to which of these hypotheses is correct, the rat 5HT2 receptor gene was transfected into NIH-3T3 cells and COS cells. Neither nontransfected cell type expresses 5HT2 receptors; the transfected cells expressed high affinity binding sites for both [125I] DOI (KD = 0.8 nM and Bmax = 363 fmol/mg in NIH-3T3 cells; KD = 0.2 nM and Bmax = 26 fmol/mg in COS cells) and [3H]ketanserin (KD = 0.4 nM and Bmax = 5034 fmol/mg in NIH-3T3 cells; KD = 1.0 nM and Bmax = 432 fmol/mg in COS cells). The affinities of agonists and antagonists for the [125I]DOI-labeled receptor were significantly higher than for the [3H]ketanserin-labeled receptor. The affinities of agonists and antagonists for these binding sites were essentially identical to their affinities for the sites radiolabeled by these radioligands in mammalian brain homogenates. The [125I]DOI binding was guanyl nucleotide sensitive, indicating a coupling to a GTP-binding protein. These data indicate that the 5HT2 receptor gene product contains both the guanyl nucleotide-sensitive [125I]DOI binding site and the [3H]ketanserin binding site. Therefore, these data indicate that the 5HT2 receptor gene product can produce a high affinity binding site for the phenylisopropylamine hallucinogen agonists as well as for the 5HT2 receptor antagonists

Multichannel heterodyne radiometers with fast-scanning backward-wave oscillators for ECE measurement on HT-7 tokamak

International Nuclear Information System (INIS)

Zhang, S.Y.; Poznyak, V.I.; Ploskirev, G.; Kalupin, D.; Wan, Y.X.; Xie, J.K.; Luo, J.R.; Li, J.G.; Gao, X.; Wan, B.N.; Zhang, X.D.; Wang, K.J.; Kuang, G.L.

2001-01-01

Two sets of fast-scanning heterodyne radiometer receiver systems employing backward-wave oscillators (BWOs) in 78-118 and 118-178 GHz were developed and installed for electron cyclotron emission (ECE) measurements on HT-7 superconducting tokamak. The double sideband (DSB) radiometer in 78-118 GHz measures 16 ECE frequency points with a scanning time period of 0.65 ms. The other radiometer in 118-178 GHz consists of one independent channel of DSB heterodyne receiver with intermediate frequency (IF) of 100-500 MHz and two channels of single sideband (SSB) heterodyne receiver that are sensitive to upper sideband and lower sideband individually; the IF frequency of the SSB channels are 1.5 GHz around the local oscillator frequencies with 1 GHz bandwidth. By employing a novel design, this unique radiometer measures 3 ECE frequency points at each of the 16 local oscillator frequency points in 118-178 GHz, and the full band can be swept in 0.65 ms period, thus the radiometer measures 48 ECE frequency points in 0.65 ms in principle. Each of the local oscillators' frequency points can be preset by program to meet specific physics interests. Horizontal view of ECE was installed to measure electron temperature profiles; vertically viewing optics along a perpendicular chord was also installed to study nonthermal ECE spectra. Preliminary measurement results were presented during ohmic and pellet injection plasmas

Design and Discovery of Functionally Selective Serotonin 2C (5-HT2C) Receptor Agonists.

Science.gov (United States)

Cheng, Jianjun; McCorvy, John D; Giguere, Patrick M; Zhu, Hu; Kenakin, Terry; Roth, Bryan L; Kozikowski, Alan P

2016-11-10

On the basis of the structural similarity of our previous 5-HT 2C agonists with the melatonin receptor agonist tasimelteon and the putative biological cross-talk between serotonergic and melatonergic systems, a series of new (2,3-dihydro)benzofuran-based compounds were designed and synthesized. The compounds were evaluated for their selectivity toward 5-HT 2A , 5-HT 2B , and 5-HT 2C receptors in the calcium flux assay with the ultimate goal to generate selective 5-HT 2C agonists. Selected compounds were studied for their functional selectivity by comparing their transduction efficiency at the G protein signaling pathway versus β-arrestin recruitment. The most functionally selective compound (+)-7e produced weak β-arrestin recruitment and also demonstrated less receptor desensitization compared to serotonin in both calcium flux and phosphoinositide (PI) hydrolysis assays. We report for the first time that selective 5-HT 2C agonists possessing weak β-arrestin recruitment can produce distinct receptor desensitization properties.

Autroadiographic characterization of 125I-labeled 2,5-dimethoxy-4-iodophenylisopropylamine (DOI): A phenylisopropylamine derivative labeling both 5HT2 and 5HT1c receptors

International Nuclear Information System (INIS)

Appel, N.M.; Mitchell, W.M.; Garlick, R.K.; Glennon, R.A.; Titeler, M.; De Souza, E.B.

1990-01-01

The best-characterized 5HT 2 radioligands, such as [ 3 H]ketanserin and [ 3 H]spiperone, are antagonists that label both high- and low-affinity states of this receptor. Recently, the radiolabeled phenylisopropylamine hallucinogens DOB and DOI, which are agonists at 5HT 2 receptors, have been demonstrated to label selectively the high-affinity state of brain 5HT 2 receptors. In the present study, the authors determined optimum conditions for autoradiographic visualization of [ 125 I]DOI binding and characterized its pharmacology and guanine nucleotide sensitivity under those conditions. In slide-mounted tissue sections (rat forebrain; two 10 μm sections/slide), (±)[ 125 I]DOI binding was saturable, of high affinity (K D ∼4nM) and displayed a pharmacological profile [R(-)DOI > spiperone > DOB > (±)DOI > ketanserin > S(+)DOI > 5HT > DOM] comparable to that seen in homogenate assays. Consistent with coupling of 5HT 2 receptors to a guanine nucleotide regulatory protein, [ 125 I]DOI binding was inhibited by guanine nucleotides but not by ATP. In autoradiograms, high densities of [ 125 I]DOI binding sites were present in frontal cortex, olfactory tubercle, claustrum, caudate/putamen and mamillary nuclei with lower densities in trigeminal and solitary nuclei. The highest density of [ 125 l]DOI binding was observed in choroid plexus; these binding sites displayed a pharmacological profile characteristic of 5HT 1C receptors. These data suggest that [ 125 I]DOI labels both 5HT 2 and 5HT 1C receptors

Equilibrium optimization code OPEQ and results of applying it to HT-7U

International Nuclear Information System (INIS)

Zha Xuejun; Zhu Sizheng; Yu Qingquan

2003-01-01

The plasma equilibrium configuration has a strong impact on the confinement and MHD stability in tokamaks. For designing a tokamak device, it is an important issue to determine the sites and currents of poloidal coils which have some constraint conditions from physics and engineering with a prescribed equilibrium shape of the plasma. In this paper, an effective method based on multi-variables equilibrium optimization is given. The method can optimize poloidal coils when the previously prescribed plasma parameters are treated as an object function. We apply it to HT-7U equilibrium calculation, and obtain good results

Activation of glucocorticoid receptors increases 5-HT2A receptor levels

DEFF Research Database (Denmark)

Trajkovska, Viktorija; Kirkegaard, Lisbeth; Krey, Gesa

2009-01-01

an effect of GR activation on 5-HT2A levels, mature organotypic hippocampal cultures were exposed to corticosterone with or without GR antagonist mifepristone and mineralocorticoid receptor (MR) antagonist spironolactone. In GR under-expressing mice, hippocampal 5-HT2A receptor protein levels were decreased......Major depression is associated with both dysregulation of the hypothalamic pituitary adrenal axis and serotonergic deficiency, not the least of the 5-HT2A receptor. However, how these phenomena are linked to each other, and whether a low 5-HT2A receptor level is a state or a trait marker...... of depression is unknown. In mice with altered glucocorticoid receptor (GR) expression we investigated 5-HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding. Serotonin fibre density was analyzed by stereological quantification of serotonin transporter immunopositive fibers. To establish...

Effects of Constant Flickering Light on Refractive Status, 5-HT and 5-HT2A Receptor in Guinea Pigs.

Science.gov (United States)

Li, Bing; Luo, Xiumei; Li, Tao; Zheng, Changyue; Ji, Shunmei; Ma, Yuanyuan; Zhang, Shuangshuang; Zhou, Xiaodong

2016-01-01

To investigate the effects of constant flickering light on refractive development, the role of serotonin (i.e.5-hydroxytryptamine, 5-HT)and 5-HT2A receptor in myopia induced by flickering light in guinea pigs. Forty-five guinea pigs were randomly divided into three groups: control, form deprivation myopia (FDM) and flickering light induced myopia (FLM) groups(n = 15 for each group). The right eyes of the FDM group were covered with semitransparent hemispherical plastic shells serving as eye diffusers. Guinea pigs in FLM group were raised with illumination of a duty cycle of 50% at a flash frequency of 0.5Hz. The refractive status, axial length (AL), corneal radius of curvature(CRC) were measured by streak retinoscope, A-scan ultrasonography and keratometer, respectively. Ultramicroscopy images were taken by electron microscopy. The concentrations of 5-HTin the retina, vitreous body and retinal pigment epithelium (RPE) were assessed by high performance liquid chromatography, the retinal 5-HT2A receptor expression was evaluated by immunohistofluorescence and western blot. The refraction of FDM and FLM eyes became myopic from some time point (the 4th week and the 6th week, respectively) in the course of the experiment, which was indicated by significantly decreased refraction and longer AL when compared with the controls (plight could cause progressive myopia in guinea pigs. 5-HT and 5-HT2A receptor increased both in form deprivation myopia and flickering light induced myopia, indicating that 5-HT possibly involved in myopic development via binding to5-HT2A receptor.

Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.

Science.gov (United States)

Newman-Tancredi, Adrian; Cussac, Didier; Quentric, Yann; Touzard, Manuelle; Verrièle, Laurence; Carpentier, Nathalie; Millan, Mark J

2002-11-01

Although certain antiparkinson agents interact with serotonin (5-HT) receptors, little information is available concerning functional actions. Herein, we characterized efficacies of apomorphine, bromocriptine, cabergoline, lisuride, piribedil, pergolide, roxindole, and terguride at human (h)5-HT(1A), h5-HT(1B), and h5-HT(1D) receptors [guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding], and at h5-HT(2A), h5-HT(2B), and h5-HT(2C) receptors (depletion of membrane-bound [(3)H]phosphatydilinositol). All drugs stimulated h5-HT(1A) receptors with efficacies (compared with 5-HT, 100%) ranging from modest (apomorphine, 35%) to high (cabergoline, 93%). At h5-HT(1B) receptors, efficacies varied from mild (terguride, 37%) to marked (cabergoline, 102%) and potencies were modest (pEC(50) values of 5.8-7.6): h5-HT(1D) sites were activated with a similar range of efficacies and greater potency (7.1-8.5). Piribedil and apomorphine were inactive at h5-HT(1B) and h5-HT(1D) receptors. At h5-HT(2A) receptors, terguride, lisuride, bromocriptine, cabergoline, and pergolide displayed potent (7.6-8.8) agonist properties (49-103%), whereas apomorphine and roxindole were antagonists and piribedil was inactive. Only pergolide (113%/8.2) and cabergoline (123%/8.6) displayed pronounced agonist properties at h5-HT(2B) receptors. At 5-HT(2C) receptors, lisuride, bromocriptine, pergolide, and cabergoline were efficacious (75-96%) agonists, apomorphine and terguride were antagonists, and piribedil was inactive. MDL100,907 and SB242,084, selective antagonists at 5-HT(2A) and 5-HT(2C) receptors, respectively, abolished these actions of pergolide, cabergoline, and bromocriptine. In conclusion, antiparkinson agents display markedly different patterns of agonist and antagonist properties at multiple 5-HT receptor subtypes. Although all show modest (agonist) activity at 5-HT(1A) sites, their contrasting actions at 5-HT(2A) and 5-HT(2C) sites may be of particular significance to their

Changes of Serotonin (5-HT), 5-HT2A Receptor, and 5-HT Transporter in the Sprague-Dawley Rats of Depression,Myocardial Infarction and Myocardial Infarction Co-exist with Depression

Institute of Scientific and Technical Information of China (English)

Mei-Yan Liu; Yah-Ping Ren; Wan-Lin Wei; Guo-Xiang Tian; Guo Li

2015-01-01

Background:To evaluate whether serotonin (5-HT),5-HT2A receptor (5-HT2AR),and 5-HT transporter (serotonin transporter [SERT]) are associated with different disease states of depression,myocardial infarction (MI) and MI co-exist with depression in Sprague-Dawley rats.Methods:After established the animal model of four groups include control,depression,MI and MI with depression,we measured 5-HT,5-HT2AR and SERT from serum and platelet lysate.Results:The serum concentration of 5-HT in depression rats decreased significantly compared with the control group (303.25 ± 9.99 vs.352.98 ± 13.73;P =0.000),while that in MI group increased (381.78 ± 14.17 vs.352.98 ± 13.73;P =0.000).However,the depression + MI group had no change compared with control group (360.62 ± 11.40 vs.352.98 ± 13.73;P =0.036).The changes of the platelet concentration of 5-HT in the depression,MI,and depression + MI group were different from that of serum.The levels of 5-HT in above three groups were lower than that in the control group (380.40 ± 17.90,387.75 ± 22.28,246.40 ± 18.99 vs.500.29 ± 20.91;P =0.000).The platelet lysate concentration of 5-HT2AR increased in depression group,MI group,and depression + MI group compared with the control group (370.75 ± 14.75,393.47 ± 15.73,446.66 ± 18.86 vs.273.66 ± 16.90;P =0.000).The serum and platelet concentration of SERT in the depression group,MI group and depression + MI group were all increased compared with the control group (527.51 ± 28.32,602.02 ± 23.32,734.76 ± 29.59 vs.490.56 ± 16.90;P =0.047,P =0.000,P =0.000 in each and 906.38 ± 51.84,897.33 ± 60.34,1030.17 ± 58.73 vs.708.62 ± 51.15;P =0.000 in each).Conclusions:The concentration of 5-HT2AR in platelet lysate and SERT in serum and platelet may be involved in the pathway of MI with depression.Further studies should examine whether elevated 5-HT2AR and SERT may contribute to the biomarker in MI patients with depression.

Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm.

Science.gov (United States)

Meyer, Jeffrey H; McMain, Shelley; Kennedy, Sidney H; Korman, Lorne; Brown, Gregory M; DaSilva, Jean N; Wilson, Alan A; Blak, Thomas; Eynan-Harvey, Rahel; Goulding, Verdell S; Houle, Sylvain; Links, Paul

2003-01-01

Dysfunctional attitudes are negatively biased assumptions and beliefs regarding oneself, the world, and the future. In healthy subjects, increasing serotonin (5-HT) agonism with a single dose of d-fenfluramine lowered dysfunctional attitudes. To investigate whether the converse, a low level of 5-HT agonism, could account for the higher levels of dysfunctional attitudes observed in patients with major depression or with self-injurious behavior, cortex 5-HT(2) receptor binding potential and dysfunctional attitudes were measured in patients with major depressive disorder, patients with a history of self-injurious behavior, and healthy comparison subjects (5-HT(2) receptor density increases during 5-HT depletion). Twenty-nine healthy subjects were recruited to evaluate the effect of d-fenfluramine or of clonidine (control condition) on dysfunctional attitudes. Dysfunctional attitudes were assessed with the Dysfunctional Attitude Scale 1 hour before and 1 hour after drug administration. In a second experiment, dysfunctional attitudes and 5-HT(2) binding potential were measured in 22 patients with a major depressive episode secondary to major depressive disorder, 18 patients with a history of self-injurious behavior occurring outside of a depressive episode, and another 29 age-matched healthy subjects. Cortex 5-HT(2) binding potential was measured with [(18)F]setoperone positron emission tomography. In the first experiment, dysfunctional attitudes decreased after administration of d-fenfluramine. In the second experiment, in the depressed group, dysfunctional attitudes were positively associated with cortex 5-HT(2) binding potential, especially in Brodmann's area 9 (after adjustment for age). Depressed subjects with extremely dysfunctional attitudes had higher 5-HT(2) binding potential, compared to healthy subjects, particularly in Brodmann's area 9. Low levels of 5-HT agonism in the brain cortex may explain the severely pessimistic, dysfunctional attitudes associated

New tritium monitor for the Tokamak Fusion Test Reactor

International Nuclear Information System (INIS)

Jalbert, R.A.

1985-01-01

At DT-fueled fusion reactors, there will be a need for tritium monitors that can simultaneously measure in real time the concentrations of HTO, HT and the activated air produced by fusion neutrons. Such a monitor has been developed, tested and delivered to the Princeton Plasma Physics Laboratory for use at the Tokamak Fusion Test Reactor (TFTR). It uses semipermeable membranes to achieve the removal of HTO from the sampled air for monitoring and a catalyst to convert the HT to HTO, also for removal and monitoring. The remaining air, devoid of tritium, is routed to a third detector for monitoring the activated air. The sensitivities are those that would be expected from tritium instruments employing conventional flow-through ionization chambers: 1 to 3 μCi/m 3 . Its discriminating ability is approximately 10 -3 for any of the three components (HTO, HT and activated air) in any of the other two channels. For instance, the concentration of HT in the HTO channel is 10 -3 times its original concentration in the sampled air. This will meet the needs of TFTR

Development of the 5-HT2CR-Tango System Combined with an EGFP Reporter Gene.

Science.gov (United States)

Watanabe, Yoshihisa; Tsujimura, Atsushi; Aoki, Miku; Taguchi, Katsutoshi; Tanaka, Masaki

2016-02-01

The serotonin 2C receptor (5-HT2CR) is a G-protein-coupled receptor implicated in emotion, feeding, reward, and cognition. 5-HT2CRs are pharmacological targets for mental disorders and metabolic and reward system abnormalities, as alterations in 5-HT2CR expression, RNA editing, and SNPs are involved in these disturbances. To date, 5-HT2CR activity has mainly been measured by quantifying inositol phosphate production and intracellular Ca(2+) release, but these assays are not suitable for in vivo analysis. Here, we developed a 5-HT2CR-Tango assay system, a novel analysis tool of 5-HT2CR activity based on the G-protein-coupled receptor (GPCR)-arrestin interaction. With desensitization of activated 5-HT2CR by arrestin, this system converts the 5-HT2CR-arrestin interaction into EGFP reporter gene signal via the LexA transcriptional activation system. For validation of our system, we measured activity of two 5-HT2CR RNA-editing isoforms (INI and VGV) in HEK293 cells transfected with EGFP reporter gene. The INI isoform displayed both higher basal- and 5-HT-stimulated activities than the VGV isoform. Moreover, an inhibitory effect of 5-HT2CR antagonist SB242084 was also detected by 5-HT2CR-Tango system. This novel tool is useful for in vitro high-throughput targeted 5-HT2CR drug screening and can be applied to future in vivo brain function studies associated with 5-HT2CRs in transgenic animal models.

Conservation of 5-HT1A receptor-mediated autoinhibition of serotonin (5-HT neurons in mice with altered 5-HT homeostasis

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Naozumi eAraragi

2013-08-01

Full Text Available Firing activity of serotonin (5-HT neurons in the dorsal raphe nucleus (DRN is controlled by inhibitory somatodendritic 5-HT1A autoreceptors. This autoinhibitory mechanism is implicated in the etiology of disorders of emotion regulation, such as anxiety disorders and depression, as well as in the mechanism of antidepressant action. Here, we investigated how persistent alterations in brain 5-HT availability affect autoinhibition in two genetically modified mouse models lacking critical mediators of serotonergic transmission: 5-HT transporter knockout (Sert -/- and tryptophan hydroxylase-2 knockout (Tph2 -/- mice. The degree of autoinhibition was assessed by loose-seal cell-attached recording in DRN slices. First, application of the 5-HT1A-selective agonist R(+-8-hydroxy-2-(di-n-propylaminotetralin showed mild sensitization and marked desensitization of 5-HT1A receptors in Tph2 -/- mice and Sert -/- mice, respectively. While 5-HT neurons from Tph2 -/- mice did not display autoinhibition in response to L-tryptophan, autoinhibition of these neurons was unaltered in Sert -/- mice despite marked desensitization of their 5-HT1A autoreceptors. When the Tph2-dependent 5-HT synthesis step was bypassed by application of 5-hydroxy-L-tryptophan (5-HTP, neurons from both Tph2 -/- and Sert -/- mice decreased their firing rates at significantly lower concentrations of 5-HTP compared to wildtype controls. Our findings demonstrate that, as opposed to the prevalent view, sensitivity of somatodendritic 5-HT1A receptors does not predict the magnitude of 5-HT neuron autoinhibition. Changes in 5-HT1A receptor sensitivity may rather be seen as an adaptive mechanism to keep autoinhibition functioning in response to extremely altered levels of extracellular 5-HT resulting from targeted inactivation of mediators of serotonergic signaling.

Occurrence of Fusarium langsethiae and T-2 and HT-2 Toxins in Italian Malting Barley.

Science.gov (United States)

Morcia, Caterina; Tumino, Giorgio; Ghizzoni, Roberta; Badeck, Franz W; Lattanzio, Veronica M T; Pascale, Michelangelo; Terzi, Valeria

2016-08-20

T-2 and HT-2 toxins are two of the most toxic members of type-A trichothecenes, produced by a number of Fusarium species. The occurrence of these mycotoxins was studied in barley samples during a survey carried out in the 2011-2014 growing seasons in climatically different regions in Italy. The percentage of samples found positive ranges from 22% to 53%, with values included between 26 and 787 μg/kg. The percentage of samples with a T-2 and HT-2 content above the EU indicative levels for barley of 200 μg/kg ranges from 2% to 19.6% in the 2011-2014 period. The fungal species responsible for the production of these toxins in 100% of positive samples has been identified as Fusarium langsethiae, a well-known producer of T-2 and HT-2 toxins. A positive correlation between the amount of F. langsethiae DNA and of the sum of T-2 and HT-2 toxins was found. This is the first report on the occurrence of F. langsethiae-and of its toxic metabolites T-2 and HT-2-in malting barley grown in Italy.

Research using small tokamaks

International Nuclear Information System (INIS)

1991-05-01

The technical reports in this document were presented at the IAEA Technical Committee Meeting ''Research on Small Tokamaks'', September 1990, in three sessions, viz., (1) Plasma Modes, Control, and Internal Phenomena, (2) Edge Phenomena, and (3) Advanced Configurations and New Facilities. In Section (1) experiments at controlling low mode number modes, feedback control using external coils, lower-hybrid current drive for the stabilization of sawtooth activity and continuous (1,1) mode, and unmodulated and fast modulated ECRH mode stabilization experiments were reported, as well as the relation to disruptions and transport of low m,n modes and magnetic island growth; static magnetic perturbations by helical windings causing mode locking and sawtooth suppression; island widths and frequency of the m=2 tearing mode; ultra-fast cooling due to pellet injection; and, finally, some papers on advanced diagnostics, i.e., lithium-beam activated charge-exchange spectroscopy, and detection through laser scattering of discrete Alfven waves. In Section (2), experimental edge physics results from a number of machines were presented (positive biasing on HYBTOK II enhancing the radial electric field and improving confinement; lower hybrid current drive on CASTOR improving global particle confinement, good current drive efficiency in HT-6B showing stabilization of sawteeth and Mirnov oscillations), as well as diagnostic developments (multi-chord time resolved soft and ultra-soft X-ray plasma radiation detection on MT-1; measurements on electron capture cross sections in multi-charged ion-atom collisions; development of a diagnostic neutral beam on Phaedrus-T). Theoretical papers discussed the influence of sheared flow and/or active feedback on edge microstability, large edge electric fields, and two-fluid modelling of non-ambipolar scrape-off layers. Section (3) contained (i) a proposal to construct a spherical tokamak ''Proto-Eta'', (ii) an analysis of ultra-low-q and runaway

Ebselen has lithium-like effects on central 5-HT2A receptor function.

Science.gov (United States)

Antoniadou, I; Kouskou, M; Arsiwala, T; Singh, N; Vasudevan, S R; Fowler, T; Cadirci, E; Churchill, G C; Sharp, T

2018-02-27

Lithium's antidepressant action may be mediated by inhibition of inositol monophosphatase (IMPase), a key enzyme in G q protein coupled receptor signalling. Recently, the antioxidant agent ebselen was identified as an IMPase inhibitor. Here we investigated both ebselen and lithium in models of the 5-HT 2A receptor, a G q protein coupled receptor implicated in lithium's actions. 5-HT 2A receptor function was modelled in mice by measuring the behavioural (head-twitches) and cortical immediate early gene (IEG; Arc, c-fos and Erg2 mRNA) responses to 5-HT 2A receptor agonist administration. Ebselen and lithium were administered either acutely or chronically prior to assessment of 5-HT 2A receptor function. Given the SSRI augmenting action of lithium and 5-HT 2A antagonists, ebselen was also tested for this action by co-administration with the SSRI citalopram in microdialysis (extracellular 5-HT) experiments. Acute and repeated administration of ebselen inhibited behavioural and IEG responses to the 5-HT 2A receptor agonist DOI. Repeated lithium also inhibited DOI-evoked behavioural and IEG responses. In comparison, a selective IMPase inhibitor (L-690,330) attenuated the behavioural response to DOI whereas glycogen synthase kinase inhibitor (AR-A014418) did not. Finally, ebselen increased regional brain 5-HT synthesis and enhanced the increase in extracellular 5-HT induced by citalopram. The current data demonstrate lithium-mimetic effects of ebselen in different experimental models of 5-HT 2A receptor function, likely mediated by IMPase inhibition. This evidence of lithium-like neuropharmacological effects of ebselen adds further support for the clinical testing of ebselen in mood disorder, including as an antidepressant augmenting agent. This article is protected by copyright. All rights reserved.

Liquid lithium surface control and its effect on plasma performance in the HT-7 tokamak

Energy Technology Data Exchange (ETDEWEB)

Zuo, G.Z.; Ren, J. [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Hu, J.S., E-mail: hujs@ipp.ac.cn [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Sun, Z.; Yang, Q.X.; Li, J.G. [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Zakharov, L.E. [Princeton University Plasma Physics Laboratory Princeton, NJ 08543 (United States); Ruzic, David N. [University of Illinois, Urbana, IL 61801 (United States)

2014-12-15

Highlights: • Strong interaction between plasma and Li would cause strong Li emission and lead to disruptive plasmas, and probable reasons were analyzed. • Serious Li would be emitted from the free statics surface mainly due to J × B force leading to plasma instable and disruptions. • CPS surface would partially suppress the emission and be beneficial for plasma operation. • Li emission from flowing LLLs on free surfaces on SS trenches and on SS plate were compared. - Abstract: Experiments with liquid lithium limiters (LLLs) have been successfully performed in HT-7 since 2009 and the effects of different limiter surface structures on the ejection of Li droplets have been studied and compared. The experiments have demonstrated that strong interaction between the plasma and the liquid surface can cause intense Li efflux in the form of ejected Li droplets – which can, in turn, lead to plasma disruptions. The details of the LLL plasma-facing surface were observed to be extremely important in determining performance. Five different LLLs were evaluated in this work: two types of static free-surface limiters and three types of flowing liquid Li (FLLL) structures. It has been demonstrated that a FLLL with a slowly flowing thin liquid Li film on vertical flow plate which was pre-treated with evaporated Li was much less susceptible to Li droplet ejection than any of the other structures tested in this work. It was further observed that the plasmas run against this type of limiter were reproducibly well-behaved. These results provide technical references for the design of FLLLs in future tokamaks so as to avoid strong Li ejection and to decrease disruptive plasmas.

Function and distribution of 5-HT2 receptors in the honeybee (Apis mellifera.

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Markus Thamm

Full Text Available BACKGROUND: Serotonin plays a pivotal role in regulating and modulating physiological and behavioral processes in both vertebrates and invertebrates. In the honeybee (Apis mellifera, serotonin has been implicated in division of labor, visual processing, and learning processes. Here, we present the cloning, heterologous expression, and detailed functional and pharmacological characterization of two honeybee 5-HT2 receptors. METHODS: Honeybee 5-HT2 receptor cDNAs were amplified from brain cDNA. Recombinant cell lines were established constitutively expressing receptor variants. Pharmacological properties of the receptors were investigated by Ca(2+ imaging experiments. Quantitative PCR was applied to explore the expression patterns of receptor mRNAs. RESULTS: The honeybee 5-HT2 receptor class consists of two subtypes, Am5-HT2α and Am5-HT2β. Each receptor gene also gives rise to alternatively spliced mRNAs that possibly code for truncated receptors. Only activation of the full-length receptors with serotonin caused an increase in the intracellular Ca(2+ concentration. The effect was mimicked by the agonists 5-methoxytryptamine and 8-OH-DPAT at low micromolar concentrations. Receptor activities were blocked by established 5-HT receptor antagonists such as clozapine, methiothepin, or mianserin. High transcript numbers were detected in exocrine glands suggesting that 5-HT2 receptors participate in secretory processes in the honeybee. CONCLUSIONS: This study marks the first molecular and pharmacological characterization of two 5-HT2 receptor subtypes in the same insect species. The results presented should facilitate further attempts to unravel central and peripheral effects of serotonin mediated by these receptors.

Function and distribution of 5-HT2 receptors in the honeybee (Apis mellifera).

Science.gov (United States)

Thamm, Markus; Rolke, Daniel; Jordan, Nadine; Balfanz, Sabine; Schiffer, Christian; Baumann, Arnd; Blenau, Wolfgang

2013-01-01

Serotonin plays a pivotal role in regulating and modulating physiological and behavioral processes in both vertebrates and invertebrates. In the honeybee (Apis mellifera), serotonin has been implicated in division of labor, visual processing, and learning processes. Here, we present the cloning, heterologous expression, and detailed functional and pharmacological characterization of two honeybee 5-HT2 receptors. Honeybee 5-HT2 receptor cDNAs were amplified from brain cDNA. Recombinant cell lines were established constitutively expressing receptor variants. Pharmacological properties of the receptors were investigated by Ca(2+) imaging experiments. Quantitative PCR was applied to explore the expression patterns of receptor mRNAs. The honeybee 5-HT2 receptor class consists of two subtypes, Am5-HT2α and Am5-HT2β. Each receptor gene also gives rise to alternatively spliced mRNAs that possibly code for truncated receptors. Only activation of the full-length receptors with serotonin caused an increase in the intracellular Ca(2+) concentration. The effect was mimicked by the agonists 5-methoxytryptamine and 8-OH-DPAT at low micromolar concentrations. Receptor activities were blocked by established 5-HT receptor antagonists such as clozapine, methiothepin, or mianserin. High transcript numbers were detected in exocrine glands suggesting that 5-HT2 receptors participate in secretory processes in the honeybee. This study marks the first molecular and pharmacological characterization of two 5-HT2 receptor subtypes in the same insect species. The results presented should facilitate further attempts to unravel central and peripheral effects of serotonin mediated by these receptors.

Experiments of full non-inductive current drive on HT-7

International Nuclear Information System (INIS)

Zhang, X.D.; Wu, Z.W.; Chen, Z.Y.; Gong, X.Z.; Wang, H.; Xu, D.; Huang, Y.; Luo, J.; Gao, X.; Hu, L.; Zhao, J.; Wan, B.N.; Li, J.

2005-01-01

Some experimental results of steady-state operation and full non-inductive current drive have been obtained on HT-7. Three types of experiment are used to study long pulse discharge, quasi-steady-state operation and full non-inductive current drive. The experiments show that the plasma current in the full non-inductive drive case is instable due to no adjusting effect of OH heating field, when the waveguide tube discharge lead to the LHW power injecting tokamak plasma decrease. This instability of plasma current will increase the interaction of plasma with limiter and first surface and bring impurity. All discharges of full non-inductive current drive are terminated because of impurity spurting. To adjust the LHW injection power for control the loop voltage during long pulse discharge is the most effective method for steady-state operation on HT-7. (author)

A Simple and Specific Noncompetitive ELISA Method for HT-2 Toxin Detection

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Henri O. Arola

2017-04-01

Full Text Available We developed an HT-2 toxin-specific simple ELISA format with a positive read-out. The assay is based on an anti-immune complex (IC scFv antibody fragment, which is genetically fused with alkaline phosphatase (AP. The anti-IC antibody specifically recognizes the IC between a primary anti-HT-2 toxin Fab fragment and an HT-2 toxin molecule. In the IC ELISA format, the sample is added together with the scFv-AP antibody to the ELISA plate coated with the primary antibody. After 15 min of incubation and a washing step, the ELISA response is read. A competitive ELISA including only the primary antibody recognizes both HT-2 and T-2 toxins. The anti-IC antibody makes the assay specific for HT-2 toxin, and the IC ELISA is over 10 times more sensitive compared to the competitive assay. Three different naturally contaminated matrices: wheat, barley and oats, were used to evaluate the assay performance with real samples. The corresponding limits of detection were 0.3 ng/mL (13 µg/kg, 0.1 ng/mL (4 µg/kg and 0.3 ng/mL (16 µg/kg, respectively. The IC ELISA can be used for screening HT-2 toxin specifically and in relevant concentration ranges from all three tested grain matrices.

Pet imaging of human pituitary 5-HT2 receptors with F-18 setoperone

Energy Technology Data Exchange (ETDEWEB)

Fischman, A.J.; Bonab, A.A.; Babich, J.W. [Massachusetts General Hospital, Boston, MA (United States)] [and others

1995-05-01

Serotonin (5-HT) receptors play an important role in the regulation of pituitary function. In particular, 5HT agonists stimulate ACTH, {beta}-endorphin, prolactin and growth hormone secretion but inhibit TSH release. 5-HT binding sites have been identified by autoradiographic studies of rat and human pituitary. In the present investigation, we used PET with F-18 setoperone to image 5-HT2 receptors in normal humans. Setoperone, a piperidine derivative with potent 5-HT2 receptor blocking properties was labelled with F-18 by nucleophilic substitution on the nitro derivative. After HPLC purification, specific activity was between 10,000 and 15,000 mCi/{mu} mole and radiochemical purity was >98%. Six healthy male volunteers were injected with 5-7 mCi of F-18. Setoperone and serial PET images and arterial blood samples were collected over 2 hrs. Specific binding to 5-HT2 receptors in the frontal cortex (FC), striatum (ST) and pituitary (P) was quantitated using the cerebellum (C) as reference. The tracer showed clear retention in FC, ST and P (known to contain a high density of 5-HT2 receptors) relative to C (known to be devoid of 5-HT2 receptors). In all subjects, FC/C, ST/C and P/C ratios increased during the first hr. and remained stable thereafter. For FC and ST, the ratios reached similar values; 3.92{plus_minus}0.73 and 3.53{plus_minus}0.32. For pituitary, a significantly higher ratio, was measured at all times; 6.53{plus_minus}1.82 (p<0.01). These results indicate that F-18 setoperone is an effective PET radiopharmaceutical for imaging 5-HT2 receptors in the human pituitary. Future applications of this agent could provide important new insights into neuroendocrine function.

Novel 7-phenylsulfanyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indoles as dual serotonin 5-HT2C and 5-HT6 receptor ligands

DEFF Research Database (Denmark)

Krogsgaard-Larsen, Niels; Jensen, Anders A.; Kehler, Jan

2010-01-01

Novel 7-phenylsulfanyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indoles are synthesized using a six-step protocol. Notably, the synthesis route make use of a new and improved ring-closing methodology for the assembly of the hexahydro-pyrazino[1,2-a]indole scaffold, which is based on intramolecular......-H insertion of a carbene. The compounds act as dual serotonin 5-HT2C- and 5-HT6-ligands....

Changes of Serotonin (5-HT, 5-HT2A Receptor, and 5-HT Transporter in the Sprague-Dawley Rats of Depression, Myocardial Infarction and Myocardial Infarction Co-exist with Depression

Directory of Open Access Journals (Sweden)

Mei-Yan Liu

2015-01-01

Conclusions: The concentration of 5-HT2AR in platelet lysate and SERT in serum and platelet may be involved in the pathway of MI with depression. Further studies should examine whether elevated 5-HT2AR and SERT may contribute to the biomarker in MI patients with depression.

Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience.

Science.gov (United States)

Pokorny, Thomas; Preller, Katrin H; Kraehenmann, Rainer; Vollenweider, Franz X

2016-04-01

The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (ppsilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Initial analysis of the HL-2A tokamak visible light measurements

International Nuclear Information System (INIS)

Shi Le; Zheng Yinjia

2005-01-01

Measurement of H α radial distribution is an important part in a plasma experiment. During the HL-2A experiment, CCD photos recorded the plasma radiation information using a plasma imaging system, particularly the H α line emission information (with H α filter in front of the camera). Since the line of light radiation measurement involves a line integral of the radiating region, data handling and analysis are necessary. The H α radial distribution along an HL-2A tokamak radial radius can be obtained by using an Abel inversion transformation with plasma imaging on the HL-2A tokamak. This paper provides a reliable measurement method on the HL-2A tokamak. (authors)

Simulations of the L-H transition on experimental advanced superconducting Tokamak

International Nuclear Information System (INIS)

Weiland, Jan

2014-01-01

We have simulated the L-H transition on the EAST tokamak [Baonian Wan, EAST and HT-7 Teams, and International Collaborators, “Recent experiments in the EAST and HT-7 superconducting tokamaks,” Nucl. Fusion 49, 104011 (2009)] using a predictive transport code where ion and electron temperatures, electron density, and poloidal and toroidal momenta are simulated self consistently. This is, as far as we know, the first theory based simulation of an L-H transition including the whole radius and not making any assumptions about where the barrier should be formed. Another remarkable feature is that we get H-mode gradients in agreement with the α – α d diagram of Rogers et al. [Phys. Rev. Lett. 81, 4396 (1998)]. Then, the feedback loop emerging from the simulations means that the L-H power threshold increases with the temperature at the separatrix. This is a main feature of the C-mod experiments [Hubbard et al., Phys. Plasmas 14, 056109 (2007)]. This is also why the power threshold depends on the direction of the grad B drift in the scrape off layer and also why the power threshold increases with the magnetic field. A further significant general H-mode feature is that the density is much flatter in H-mode than in L-mode

The recovery of 5-HT transporter and 5-HT immunoreactivity in injured rat spinal cord.

Science.gov (United States)

Saruhashi, Yasuo; Matsusue, Yoshitaka; Fujimiya, Mineko

2009-09-01

Experimental spinal cord injury. To determine the role of serotonin (5-HT) and 5-HT transporter in recovery from spinal cord injury. We examined 5-HT and 5-HT transporter of spinal cord immunohistologically and assessed locomotor recovery after extradural compression at the thoracic (T8) spinal cord in 21 rats. Eighteen rats had laminectomy and spinal cord injury, while the remaining three rats received laminectomy only. All rats were evaluated every other day for 4 weeks, using a 0-14 point scale open field test. Extradural compression markedly reduced mean hindlimbs scores from 14 to 1.5 +/- 2.0 (mean +/- standard error of mean). The rats recovered apparently normal walking by 4 weeks. The animals were perfused with fixative 1-3 days, 1, 2 and 4 weeks (three rats in each) after a spinal cord injury. The 5-HT transporter immunohistological study revealed a marked reduction of 5-HT transporter-containing terminals by 1 day after injury. By 4 weeks after injury, 5-HT transporter immunoreactive terminals returned to the control level. The 5-HT immunohistological study revealed a reduction of 5-HT-containing terminals by 1 week after injury. By 4 weeks after injury, 5-HT immunoreactive fibers and terminals returned to the control level. We estimated the recovery of 5-HT transporter and 5-HT neural elements in lumbosacral ventral horn by ranking 5-HT transporter and 5-HT staining intensity and counting 5-HT and 5-HT transporter terminals. The return of 5-HT transporter and 5-HT immunoreactivity of the lumbosacral ventral horn correlated with locomotor recovery, while 5-HT transporter showed closer relationship with locomotor recovery than 5-HT. The presence of 5-HT transporter indicates that the 5-HT fibers certainly function. This study shows that return of the function of 5-HT fibers predict the time course and extent of locomotory recovery after thoracic spinal cord injury.

5-HT2C Receptor Desensitization Moderates Anxiety in 5-HTT Deficient Mice: From Behavioral to Cellular Evidence

Science.gov (United States)

Martin, Cédric BP; Martin, Vincent S.; Trigo, José M.; Chevarin, Caroline; Maldonado, Rafael; Fink, Latham H.; Cunningham, Kathryn A.; Hamon, Michel; Lanfumey, Laurence

2015-01-01

Background: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas. Methods: Mice lacking the 5-HT reuptake carrier (5-HTT-/-) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR–induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos–induced expression) levels. Results: Although 5-HTT-/- mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR–mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR–mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT-/- mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT-/- mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR–like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT-/- mutants. Conclusions: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT-/- mice. PMID:25522398

Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster

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Wolfgang Blenau

2017-05-01

Full Text Available Serotonin (5-hydroxytryptamine, 5-HT is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects and deuterostomes (e.g., mammals. In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In Drosophila melanogaster, a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT1A, Dm5-HT1B, and Dm5-HT7 couple to cAMP signaling cascades, the Dm5-HT2A receptor leads to Ca2+ signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth D. melanogaster gene was uncovered coding for a Dm5-HT2B receptor. Knowledge about this receptor’s pharmacological properties is very limited. This is quite surprising because Dm5-HT2B has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT2B mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT2B’s pharmacology, we evaluated the receptor’s response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT2B signaling in vitro and in vivo.

Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster.

Science.gov (United States)

Blenau, Wolfgang; Daniel, Stöppler; Balfanz, Sabine; Thamm, Markus; Baumann, Arnd

2017-01-01

Serotonin (5-hydroxytryptamine, 5-HT) is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects) and deuterostomes (e.g., mammals). In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In Drosophila melanogaster , a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT 1A , Dm5-HT 1B , and Dm5-HT 7 couple to cAMP signaling cascades, the Dm5-HT 2A receptor leads to Ca 2+ signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth D. melanogaster gene was uncovered coding for a Dm5-HT 2B receptor. Knowledge about this receptor's pharmacological properties is very limited. This is quite surprising because Dm5-HT 2B has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT 2B mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT 2B 's pharmacology, we evaluated the receptor's response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT 2B signaling in vitro and in vivo .

Magnetic sensorless control experiment without drift problem on HT-7

International Nuclear Information System (INIS)

Nakamura, K.; Luo, J.R.; Wang, H.Z.; Ji, Z.S.; Wang, H.; Wang, F.; Qi, N.; Sato, K.N.; Hanada, K.; Sakamoto, M.; Idei, H.; Hasegawa, M.; Iyomasa, A.; Kawasaki, S.; Nakashima, H.; Higashijima, A.

2006-01-01

Magnetic sensorless control experiments of the plasma horizontal position have been carried out in the superconducting tokamak HT-7. Previously the horizontal position was calculated from the vertical field coil current and voltage without using signals of magnetic sensors like magnetic coils and flux loops placed near the plasma. The calculations are made focusing on the ripple frequency component of the power supply with thyristor and directly from them without time integration. There is no drift problem of integrator of magnetic sensors. Two kinds of experiments were carried out, to keep the position constant and swing the position in a triangular waveform

PPPL tokamak program

International Nuclear Information System (INIS)

Furth, H.P.

1984-10-01

The economic prospects of the tokamak are reviewed briefly and found to be favorable - if the size of ignited tokamak plasmas can be kept small and appropriate auxiliary systems can be developed. The main objectives of the Princeton Plasma Physics Laboratory tokamak program are: (1) exploration of the physics of high-temperature toroidal confinement, in TFTR; (2) maximization of the tokamak beta value, in PBX; (3) development of reactor-relevant rf techniques, in PLT

Reduced 5-HT2A receptor binding in patients with mild cognitive impairment

DEFF Research Database (Denmark)

Hasselbalch, S G; Madsen, K; Svarer, C

2008-01-01

cerebral 5-HT(2A) receptor binding in patients with mild cognitive impairment (MCI) and related 5-HT(2A) receptor binding to clinical symptoms. Sixteen patients with MCI of the amnestic type (mean age 73, mean MMSE 26.1) and 17 age and sex matched control subjects were studied with MRI and [(18)F......Previous studies of patients with Alzheimer's disease (AD) have described reduced brain serotonin 2A (5-HT(2A)) receptor density. It is unclear whether this abnormality sets in early in the course of the disease and whether it is related to early cognitive and neuropsychiatric symptoms. We assessed...

Synthesis and evaluation of 18F-labeled 5-HT2A receptor agonists as PET ligands

International Nuclear Information System (INIS)

Herth, Matthias M.; Petersen, Ida Nymann; Hansen, Hanne Demant; Hansen, Martin; Ettrup, Anders; Jensen, Anders A.; Lehel, Szabolcs; Dyssegaard, Agnete; Gillings, Nic; Knudsen, Gitte M.

2016-01-01

Introduction: The serotonin 2A receptor (5-HT 2A R) is the most abundant excitatory 5-HT receptor in the human brain and implicated in various brain disorders such as schizophrenia, depression, and Alzheimer's disease. Positron emission tomography (PET) can be used to image specific proteins and processes in the human brain and several 5-HT 2A R PET antagonist radioligands are available. In contrast to an antagonist radioligand, an agonist radioligand should be able to image the population of functional receptors, i.e., those capable of inducing neuroreceptor signaling. Recently, we successfully developed and validated the first 5-HT 2A R agonist PET tracer, [ 11 C]Cimbi-36, for neuroimaging in humans and herein disclose some of our efforts to develop an 18 F-labeled 5-HT 2A R agonist PET-ligand. Methods and results: Three fluorine containing derivatives of Cimbi-36 were synthesized and found to be potent 5-HT 2A agonists. 18 F-labeling of the appropriate precursors was performed using [ 18 F]FETos, typically yielding 0.2–2.0 GBq and specific activities of 40–120 GBq/μmol. PET studies in Danish landrace pigs revealed that [ 18 F]1 displayed brain uptake in 5-HT 2A R rich regions. However, high uptake in bone was also observed. No blocking effect was detected during a competition experiment with a 5-HT 2A R selective antagonist. [ 18 F]2 and [ 18 F]3 showed very low brain uptake. Conclusion: None of the investigated 18 F-labeled Cimbi-36 derivatives [ 18 F]1, [ 18 F]2 and [ 18 F]3 show suitable tracer characteristics for in vivo PET neuroimaging of the 5-HT 2A R. Although for [ 18 F]1 there was reasonable brain uptake, we suggest that a large proportion radioactivity in the brain was due to radiometabolites, which would explain why it could not be displaced by a 5-HT 2A R antagonist.

Current radiosynthesis strategies for 5-HT2A receptor PET tracers

DEFF Research Database (Denmark)

Herth, Matthias M; Knudsen, Gitte M

2015-01-01

Serotonin 2A receptors have been implicated in various psychophysiological functions and disorders such as depression, Alzheimer's disease, or schizophrenia. Therefore, neuroimaging of this specific receptor is of significant clinical interest, and it is not surprising that many attempts have been...... made to develop a suitable 5-HT2A R positron emission tomography-tracer. In this review, we give an overview on the precursor, reference compound synthesis, and the preparation of promising 5-HT2A R radiopharmaceuticals applied in positron emission tomography. We also highlight possible learning...

Fluoxetine-induced inhibition of synaptosomal [3H]5-HT release: Possible Ca2+-channel inhibition

International Nuclear Information System (INIS)

Stauderman, K.A.; Gandhi, V.C.; Jones, D.J.

1992-01-01

Fluoxetine, a selective 5-Ht uptake inhibitor, inhibited 15 mM K + -induced [ 3 H]5-HT release from rat spinal cord and cortical synaptosomes at concentrations > 0.5 uM. This effect reflected a property shared by another selective 5-HT uptake inhibitor paroxetine but not by less selective uptake inhibitors such as amitriptyline, desipramine, imipramine or nortriptyline. Inhibition of release by fluoxetine was inversely related to both the concentration of K + used to depolarize the synaptosomes and the concentration of external Ca 2+ . Experiments aimed at determining a mechanism of action revealed that fluoxetine did not inhibit voltage-independent release of [ 3 H]5-HT release induced by the Ca 2+ -ionophore A 23187 or Ca 2+ -independent release induced by fenfluramine. Moreover the 5-HT autoreceptor antagonist methiothepin did not reverse the inhibitory actions of fluoxetine on K + -induced release. Further studies examined the effects of fluoxetine on voltage-dependent Ca 2+ channels and Ca 2+ entry

Functional expression of 5-HT{sub 2A} receptor in osteoblastic MC3T3-E1 cells

Energy Technology Data Exchange (ETDEWEB)

Hirai, Takao; Kaneshige, Kota; Kurosaki, Teruko [Department of Molecular Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Gakuen-cho, Fukuyama, Hiroshima 729-0292 (Japan); Nishio, Hiroaki, E-mail: nishio@fupharm.fukuyama-u.ac.jp [Department of Molecular Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Gakuen-cho, Fukuyama, Hiroshima 729-0292 (Japan)

2010-05-28

In the previous study, we reported the gene expression for proteins related to the function of 5-hydroxytryptamine (5-HT, serotonin) and elucidated the expression patterns of 5-HT{sub 2} receptor subtypes in mouse osteoblasts. In the present study, we evaluated the possible involvement of 5-HT receptor subtypes and its inactivation system in MC3T3-E1 cells, an osteoblast cell line. DOI, a 5-HT{sub 2A} and 5-HT{sub 2C} receptor selective agonist, as well as 5-HT concentration-dependently increased proliferative activities of MC3T3-E1 cells in their premature period. This effect of 5-HT on cell proliferation were inhibited by ketanserin, a 5-HT{sub 2A} receptor specific antagonist. Moreover, both DOI-induced cell proliferation and phosphorylation of ERK1 and 2 proteins were inhibited by PD98059 and U0126, selective inhibitors of MEK in a concentration-dependent manner. Furthermore, treatment with fluoxetine, a 5-HT specific re-uptake inhibitor which inactivate the function of extracellular 5-HT, significantly increased the proliferative activities of MC3T3-E1 cells in a concentration-dependent manner. Our data indicate that 5-HT fill the role for proliferation of osteoblast cells in their premature period. Notably, 5-HT{sub 2A} receptor may be functionally expressed to regulate mechanisms underlying osteoblast cell proliferation, at least in part, through activation of ERK/MAPK pathways in MC3T3-E1 cells.

Tianeptine: 5-HT uptake sites and 5-HT(1-7) receptors modulate memory formation in an autoshaping Pavlovian/instrumental task.

Science.gov (United States)

Meneses, Alfredo

2002-05-01

Recent studies using invertebrate and mammal species have revealed that, endogenous serotonin (5-hydroxytryptamine, 5-HT) modulates cognitive processes, particularly learning and memory, though, at present, it is unclear the manner, where, and how long 5-HT systems are involved. Hence in this work, an attempt was made to study the effects of 5-HT endogenous on memory formation, using a 5-HT uptake facilitator (tianeptine) and, selective 5-HT(1-7) receptor antagonists to determine whether 5-HT uptake sites and which 5-HT receptors are involved, respectively. Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task, which has been useful to detect changes on memory formation elicited by drugs or aging. On interaction experiments, ketanserin (5-HT(1D/2A/2C) antagonist) slightly enhanced tianeptine effects, while WAY 100635 (5-HT(1A) antagonist), SB-224289 (5-HT(1B) inverse agonist), SB-200646 (5-HT(2B/2C) antagonist), ondansetron (5-HT(3) antagonist), GR 127487 (5-HT(4) antagonist), Ro 04-6790 (5-HT(6) antagonist), DR 4004 (5-HT(7) antagonist), or fluoxetine (an inhibitor of 5-HT reuptake) blocked the facilitatory tianeptine effect. Notably, together tianeptine and Ro 04-6790 impaired learning consolidation. Moreover, 5-HT depletion completely reversed the tianeptine effect. Tianeptine also normalized an impaired memory elicited by scopolamine (an antimuscarinic) or dizocilpine (non-competitive glutamatergic antagonist), while partially reversed that induced by TFMPP (5-HT(1B/1D/2A-2C/7) agonist/antagonist). Finally, tianeptine-fluoxetine coadministration had no effect on learning consolidation; nevertheless, administration of an acetylcholinesterase inhibitor, phenserine, potentiated subeffective tianeptine or fluoxetine doses. Collectively, these data confirmed that endogenously 5-HT modulates, via uptake sites and 5-HT(1-7) receptors, memory consolidation, and are consistent with the

5-HT2 and 5-HT7 receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons

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Urszula eSlawinska

2014-08-01

Full Text Available There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT1A/7 receptors leads to activation of the spinal cord circuitry for locomotion. These receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used agonists that are efficient in promoting locomotor recovery in paraplegic rats, 8-OHDPAT (acting on 5-HT1A/7 receptors and quipazine (acting on 5-HT2 receptors, to examine this issue. Analysis of intra- and interlimb coordination confirmed that the locomotor performance was significantly improved by either drug, but the data revealed marked differences in their mode of action. Interlimb coordination was significantly better after 8-OHDPAT application, and the activity of the extensor soleus muscle was significantly longer during the stance phase of locomotor movements enhanced by quipazine. Our results show that activation of both receptors facilitates locomotion, but their effects are likely exerted on different populations of spinal neurons. Activation of 5-HT2 receptors facilitates the output stage of the locomotor system, in part by directly activating motoneurons, and also through activation of interneurons of the locomotor CPG. Activation of 5-HT7/1A receptors facilitates the activity of the locomotor CPG, without direct actions on the output components of the locomotor system, including motoneurons. Although our findings show that the combined use of these two drugs results in production of well-coordinated weight supported locomotion with a reduced need for exteroceptive stimulation, they also indicate that there might be some limitations to the utility of combined treatment. Sensory feedback and some intraspinal circuitry recruited by the drugs can conflict with the locomotor activation.

Synthesis and evaluation of 18F-labeled 5-HT2A receptor agonists as PET ligands

DEFF Research Database (Denmark)

Herth, Matthias M; Petersen, Ida Nymann; Hansen, Hanne Demant

2016-01-01

INTRODUCTION: The serotonin 2A receptor (5-HT2AR) is the most abundant excitatory 5-HT receptor in the human brain and implicated in various brain disorders such as schizophrenia, depression, and Alzheimer's disease. Positron emission tomography (PET) can be used to image specific proteins...... to be potent 5-HT2A agonists. (18)F-labeling of the appropriate precursors was performed using [(18)F]FETos, typically yielding 0.2-2.0GBq and specific activities of 40-120GBq/μmol. PET studies in Danish landrace pigs revealed that [(18)F]1 displayed brain uptake in 5-HT2AR rich regions. However, high uptake...

Advanced statistics for tokamak transport colinearity and tokamak to tokamak variation

International Nuclear Information System (INIS)

Riedel, K.S.

1989-03-01

This is a compendium of three separate articles on the statistical analysis of tokamak transport. The first article is an expository introduction to advanced statistics and scaling laws. The second analyzes two important problems of tokamak data---colinearity and tokamak to tokamak variation in detail. The third article generalizes the Swamy random coefficient model to the case of degenerate matrices. Three papers have been processed separately

Envolvimento de receptores 5-HT2C do hipocampo ventral em comportamentos de defesa de ratos no labirinto em cruz elevado Involvement of ventral hippocampus 5-HT2C receptors on defensive behaviors of rats in the elevated plus-maze

Directory of Open Access Journals (Sweden)

Marília Greidinger Carvalho

2012-04-01

Full Text Available A ativação farmacológica dos receptores 5-HT2C induz comportamentos de defesa em modelos animais. O estudo busca investigar se o bloqueio seletivo de receptores 5-HT2C no hipocampo ventral (HV previne comportamentos defensivos induzidos por um agonista de receptor 5-HT2C administrado perifericamente em ratos expostos ao labirinto em cruz elevado (LCE. Quinze minutos após injeções intraperitoniais (IP, 1ml/kg do agonista 5-HT2C WAY-161503, ratos foram microinjetados bilateralmente no HV com o antagonista seletivo de receptores 5-HT2C SB-242084 (0, 0,1, 0,5 ou 1.5μg. Dez minutos após, cada animal foi exposto ao LCE para o registro de categorias de ansiedade. Injeções sistêmicas do WAY-161503 reduziram seletivamente as explorações nos braços abertos e aumentaram padrões de avaliação de risco. Esse efeito foi atenuado de maneira dose-dependente pela microinjeção de SB-242084 no HV, confirmando a ação ansiogênica de agonistas 5-HT2C e sugerindo que esse perfil comportamental seja mediado, pelo menos em parte, por receptores 5-HT2C do HV.Pharmacological 5-HT2C receptor activation induces defensive behaviors in several animal models of anxiety. The present study investigated whether the selective blockade of 5-HT2C receptors in the ventral hippocampus (VH prevents defensive behaviors induced by a 5-HT2C agonist administered systemically in rats exposed to the elevated plus-maze (EPM. Fifteen minutes after intraperitonial (IP, 1ml/kg injections of the selective 5-HT2C receptor agonist WAY-161503 (3 mg/kg, rats were bilaterally microinjected with the selective 5-HT2C antagonist SB-242084 (0, 0.1, 0.5 or 1.5μg into the VH. Ten minutes after, each animal was exposed to the EPM for measuring classical and ethological anxiety measures. IP WAY-161503 injections selectively decreased open-arm exploration while increasing risk-assessment. This anxiogenic-like action was dose-dependently attenuated by intra-VH SB-242084 microinjections

Radioligands for brain 5-HT2 receptor imaging in vivo: why do we need them?

International Nuclear Information System (INIS)

Busatto, G.F.

1996-01-01

Recently, PET and SPET radiotracers with high specificity for 5-HT 2 receptors have been developed. These have been studied in baboons and humans with promising results, displaying a binding profile compatible with the brain distribution of 5-HT 2 receptors. It is predicted that studies with the newly developed 5-HT radioligands will substantially increase knowledge about the pharmacology of brain disorders. (orig./MG)

Near-wall effects in improved plasma confinement regimes in tokamak FT-2

International Nuclear Information System (INIS)

Budnikov, V.N.; D'yachenko, V.V.; Esipov, L.A.

1997-01-01

Transition to the regime of improved plasma confinement (H-mode) revealed in experiments on low hybrid heating in tokamak ft-2 is analyzed. Main attention is paid to processes, taking place in near-wall region. The data are correlated with results of experiments in large tokamaks

Postirradiation examination report of TRISO and BISO coated ThO2 particles irradiated in capsules HT-31 and HT-33

International Nuclear Information System (INIS)

Sedlak, B.J.

1980-01-01

Capsules HT-31 and HT-33 were uninstrumented capsule experiments irradiated in the target position of the High-Flux Isotope Reactor at Oak Ridge National Laboratory. The experiments were used to evaluate the irradiation performance of (1) fuel fabricated in a 240-mm-diameter coater for production scale-up, (2) TRISO ThO 2 and BISO ThO 2 particles, and (3) fuel with certain OPyC variables. A total of 16 BISO particle samples and 32 TRISO particle samples were irradiated to fast neutron fluences ranging from 4.0 to 11.7 x 10 25 n/m 2 (E > 29 fJ)/sub HTGR/ and heavy metal burnups between 3.5% and 13.2% FIMA at temperatures from 1150 0 to 1530 0 C

Recent advances in the HL-2A tokamak experiments

International Nuclear Information System (INIS)

Liu, Y.; Ding, X.T.; Yang, Q.W.; Yan, L.W.; Liu, D.Q.; Xuan, W.M.; Chen, L.Y.; Song, X.M.; Cao, Z.; Zhang, J.H.; Mao, W.C.; Zhou, C.P.; Li, X.D.; Wang, S.J.; Yan, J.C.; Bu, M.N.; Chen, Y.H.; Cui, C.H.; Cui, Z.Y.; Deng, Z.C.; Hong, W.Y.; Hu, H.T.; Huang, Y.; Kang, Z.H.; Li, B.; Li, W.; Li, F.Z.; Li, G.S.; Li, H.J.; Li, Q.; Li, Y.G.; Li, Z.J.; Liu, Yi; Liu, Z.T.; Luo, C.W.; Mao, X.H.; Pan, Y.D.; Rao, J.; Shao, K.; Song, X.Y.; Wang, M.; Wang, M.X.; Wang, Q.M.; Xiao, Z.G.; Xie, Y.F.; Yao, L.H.; Yao, L.Y.; Zheng, Y.J.; Zhong, G.W.; Zhou, Y.; Pan, C.H.

2005-01-01

Two experiment campaigns were conducted on the HL-2A tokamak in 2003 and 2004 after the first plasma was obtained at the end of 2002. Progresses in many aspects have been made, especially in the divertor discharge and feedback control of plasma configuration. Up to now, the following operation parameters have been achieved: I p = 320 kA, B t = 2.2 T and discharge duration T d = 1580 ms. With the feedback control of plasma current and horizontal position, an excellent repeatability of the discharge has been achieved. The tokamak has been operated at both limiter configuration and single null (SN) divertor configuration. The HL-2A SN divertor configuration is simulated with the MHD equilibrium code SWEQU. When the divertor configuration is formed, the impurity radiation in the main plasma decreases remarkably

The possible role of Reynolds stress in the creation of a transport barrier in tokamak edge plasmas

International Nuclear Information System (INIS)

Vergote, M.; Van Schoor, M.; Xu, Y.; Jachmich, S.; Weynants, R.; Hron, M.; Stoeckel, J.

2005-01-01

To obtain a good confinement, mandatory in a fusion reactor, the understanding of the formation of transport barriers in the edge plasma of a tokamak is essential. Turbulence, the major candidate to explain anomalous transport, can be quenched by sheared flows in the edge which rip the convective cells apart, thus forming a barrier. Experimental evidence from the Chinese HT-6M tokamak [Y.H. Xu et al.: Phys. Rev. Lett. 84 (2000) 3867], points to the fact that momentum transfer from the turbulence can create these sheared flows via the Reynolds stresses. A new 1-d fluid model for the generation of the poloidal flow, has been developed taking into account the driving force of the Reynolds stress and the friction forces due to neutrals and parallel viscosity. Special attention has been dedicated to the computation of the flux-surface-averaging for the various terms. This model has been confronted with the experimental results obtained in the HT-6M tokamak, where Reynolds stresses were generated by application of a turbulent heating pulse. If the model is applied in cylindrical geometry, the calculated Reynolds stress-induced flow agrees well with the measured poloidal velocity in the plasma edge. However, when the full toroidal geometry is taken into account, it seems that the Reynolds stresses are too small to explain the observed rotation. This indicates that the role of the Reynolds stresses in inducing macroscopic flow in the torus is weakened. A combined system of probes allowing to measure the Reynolds stress and the rotation velocity simultaneously, has been developed and installed on the CASTOR tokamak. We report here on the first results obtained. (author)

Characterization of [(11)C]Cimbi-36 as an agonist PET radioligand for the 5-HT(2A) and 5-HT(2C) receptors in the nonhuman primate brain

DEFF Research Database (Denmark)

Finnema, Sjoerd J; Stepanov, Vladimir; Ettrup, Anders

2014-01-01

a more meaningful assessment of available receptors than antagonist radioligands. In the current study we characterized [(11)C]Cimbi-36 receptor binding in the primate brain. On five experimental days, a total of 14 PET measurements were conducted in three female rhesus monkeys. On each day, PET...... agonist radioligand suitable for examination of 5-HT2A receptors in the cortical regions and of 5-HT2C receptors in the choroid plexus of the primate brain....

Behavior of oxygen impurities in tokamak. Vol. 2

Energy Technology Data Exchange (ETDEWEB)

El-Sharif, R N; Beket, A H [Plasma and Nuclear Fusion Department, Nuclear Research Center, Atomic Energy Aurhority, Cairo (Egypt)

1996-03-01

Impurity transport in tokamak plasma is a subject of great importance in present day tokamak experiments. The transport of oxygen as an impurity element in small tokamak was studied theoretically. The viscosity coefficient of oxygen has been calculated in different approximation 13 and 21 moment approximation, taking into consideration {chi}>>1,{chi}{omega}{sub c} {tau}. It was found that in 21 moment approximation additional terms added to the perturbation from equilibrium leads to increase in viscosity coefficients than in 13 moments approximation. 9 figs.

Oppositional effects of serotonin receptors 5-HT1a, 2 and 2c in the regulation of adult hippocampal neurogenesis

Directory of Open Access Journals (Sweden)

Friederike Klempin

2010-07-01

Full Text Available Serotonin (5-HT appears to play a major role in controlling adult hippocampal neurogenesis and thereby it is relevant for theories linking failing adult neurogenesis to the pathogenesis of major depression and the mechanisms of action of antidepressants. Serotonergic drugs lack acute effects on adult neurogenesis in many studies, which suggests a surprising long latency phase. Here we report that the selective serotonin reuptake inhibitor fluoxetine, which has no acute effect on precursor cell proliferation, causes the well-described increase in net neurogenesis upon prolonged treatment partly by promoting the survival and maturation of new postmitotic neurons. We hypothesized that this result is the cumulative effect of several 5-HT-dependent events in the course of adult neurogenesis. Thus, we used specific agonists and antagonists to 5-HT1a, 2, and 2c receptor subtypes to analyze their impact on different developmental stages. We found that 5-HT exerts acute and opposing effects on proliferation and survival or differentiation of precursor cells by activating the diverse receptor subtypes on different stages within the neuronal lineage in vivo. This was confirmed in vitro by demonstrating that 5-HT1a receptors are involved in self-renewal of precursor cells, whereas 5-HT2 receptors effect both proliferation and promote neuronal differentiation. We propose that under acute conditions 5-HT2 effects counteract the positive proliferative effect of 5-HT1a receptor activation. However, prolonged 5-HT2c receptor activation fosters an increase in late stage progenitor cells and early postmitotic neurons, leading to a net increase in adult neurogenesis. Our data indicate that serotonin does not show effect latency in the adult dentate gyrus. Rather, the delayed response to serotonergic drugs with respect to endpoints downstream of the immediate receptor activity is largely due to the initially antagonistic and un-balanced action of different 5-HT

Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes.

Science.gov (United States)

Bianchi, M; Moser, C; Lazzarini, C; Vecchiato, E; Crespi, F

2002-03-01

Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the

Concept definition of KT-2, a large-aspect-ratio diverter tokamak with FWCD

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Kyoo; Chang, In Soon; Chung, Moon Kyoo; Hwang, Chul Kyoo; Lee, Kwang Won; In, Sang Ryul; Choi, Byung Ho; Hong, Bong Keun; Oh, Byung Hoon; Chung, Seung Ho; Yoon, Byung Joo; Yoon, Jae Sung; Song, Woo Sub [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Chang, Choong Suk; Chang, Hong Yung; Choi, Duk In; Nam, Chang Heui [Korea Advanced Inst. of Science and Technology, Taejon (Korea, Republic of); Chung, Kyoo Sun [Hanyang Univ., Seoul (Korea, Republic of); Hong, Sang Heui [Seoul National Univ., Seoul (Korea, Republic of); Kang, Heui Dong [Kyungpook National Univ., Taegu (Korea, Republic of); Lee, Jae Koo [Pohang Inst. of Science and Technology, Kyungnam (Korea, Republic of)

1994-11-01

A concept definition of the KT-2 tokamak is made. The research goal of the machine is to study the `advanced tokamak` physics and engineering issues on the mid size large-aspect-ratio diverter tokamak with intense RF heating (>5 MW). Survey of the status of the research fields, the physics basis for the concept, operation scenarios, as well as machine design concept are presented. (Author) 86 refs., 17 figs., 22 tabs.

Concept definition of KT-2, a large-aspect-ratio diverter tokamak with FWCD

International Nuclear Information System (INIS)

Kim, Sung Kyoo; Chang, In Soon; Chung, Moon Kyoo; Hwang, Chul Kyoo; Lee, Kwang Won; In, Sang Ryul; Choi, Byung Ho; Hong, Bong Keun; Oh, Byung Hoon; Chung, Seung Ho; Yoon, Byung Joo; Yoon, Jae Sung; Song, Woo Sub; Chang, Choong Suk; Chang, Hong Yung; Choi, Duk In; Nam, Chang Heui; Chung, Kyoo Sun; Hong, Sang Heui; Kang, Heui Dong; Lee, Jae Koo

1994-11-01

A concept definition of the KT-2 tokamak is made. The research goal of the machine is to study the 'advanced tokamak' physics and engineering issues on the mid size large-aspect-ratio diverter tokamak with intense RF heating (>5 MW). Survey of the status of the research fields, the physics basis for the concept, operation scenarios, as well as machine design concept are presented. (Author) 86 refs., 17 figs., 22 tabs

Quasi-steady-state operation around operational limit in HT-7

International Nuclear Information System (INIS)

Li, J.; Xie, J.K.; Wan, B.N.; Luo, J.R.; Gao, X.; Zhao, Y.; Yang, Y.; Kuang, G.L.; Bao, Y.; Ding, B.J.; Wan, Y.X.

2001-01-01

Efforts have been made on HT-7 tokamak for extending the stable operation boundaries. Extensive RF boronization and siliconization have been used and wider operational Hugill diagram was obtained. Transit density reached 1.3 time of Greenwald density limit in ohmic discharges. Stationary high performance discharge with q a =2.1 has been obtained after siliconization. Confinement improvement was obtained due to the significant reduction of electron thermal diffusivity χ e in the out region of the plasma. Improved confinement phase was also observed by LHCD under the density range 70%∼120% of Greenwald density limit. The weak hollow current density profile was attribute to off-axis LHW power deposition. Code simulations and measurements showed a good agreement of off-axis LHW deposition. Supersonic molecular beam injection has been successfully used to get stable high-density operation in the range of Greenwald density limit. (author)

Repeated 7-Day Treatment with the 5-HT2C Agonist Lorcaserin or the 5-HT2A Antagonist Pimavanserin Alone or in Combination Fails to Reduce Cocaine vs Food Choice in Male Rhesus Monkeys.

Science.gov (United States)

Banks, Matthew L; Negus, S Stevens

2017-04-01

Cocaine use disorder is a global public health problem for which there are no Food and Drug Administration-approved pharmacotherapies. Emerging preclinical evidence has implicated both serotonin (5-HT) 2C and 2A receptors as potential mechanisms for mediating serotonergic attenuation of cocaine abuse-related neurochemical and behavioral effects. Therefore, the present study aim was to determine whether repeated 7-day treatment with the 5-HT 2C agonist lorcaserin (0.1-1.0 mg/kg per day, intramuscular; 0.032-0.1 mg/kg/h, intravenous) or the 5-HT 2A inverse agonist/antagonist pimavanserin (0.32-10 mg/kg per day, intramuscular) attenuated cocaine reinforcement under a concurrent 'choice' schedule of cocaine and food availability in rhesus monkeys. During saline treatment, cocaine maintained a dose-dependent increase in cocaine vs food choice. Repeated pimavanserin (3.2 mg/kg per day) treatments significantly increased small unit cocaine dose choice. Larger lorcaserin (1.0 mg/kg per day and 0.1 mg/kg/h) and pimavanserin (10 mg/kg per day) doses primarily decreased rates of operant behavior. Coadministration of ineffective lorcaserin (0.1 mg/kg per day) and pimavanserin (0.32 mg/kg per day) doses also failed to significantly alter cocaine choice. These results suggest that neither 5-HT 2C receptor activation nor 5-HT 2A receptor blockade are sufficient to produce a therapeutic-like decrease in cocaine choice and a complementary increase in food choice. Overall, these results do not support the clinical utility of 5-HT 2C agonists and 5-HT 2A inverse agonists/antagonists alone or in combination as candidate anti-cocaine use disorder pharmacotherapies.

5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease.

Science.gov (United States)

Ferguson, Marcus C; Nayyar, Tultul; Deutch, Ariel Y; Ansah, Twum A

2010-01-01

Clinical observations have suggested that ritanserin, a 5-HT(2A/C) receptor antagonist may reduce motor deficits in persons with Parkinson's Disease (PD). To better understand the potential antiparkinsonian actions of ritanserin, we compared the effects of ritanserin with the selective 5-HT(2A) receptor antagonist M100907 and the selective 5-HT(2C) receptor antagonist SB 206553 on motor impairments in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP-treated mice exhibited decreased performance on the beam-walking apparatus. These motor deficits were reversed by acute treatment with L-3,4-dihydroxyphenylalanine (levodopa). Both the mixed 5-HT(2A/C) antagonist ritanserin and the selective 5-HT(2A) antagonist M100907 improved motor performance on the beam-walking apparatus. In contrast, SB 206553 was ineffective in improving the motor deficits in MPTP-treated mice. These data suggest that 5-HT(2A) receptor antagonists may represent a novel approach to ameliorate motor symptoms of Parkinson's disease. Published by Elsevier Ltd.

Both exogenous 5-HT and endogenous 5-HT, released by fluoxetine, enhance distension evoked propulsion in guinea-pig ileum in vitro

Directory of Open Access Journals (Sweden)

Rachel M Gwynne

2014-09-01

Full Text Available The roles of 5-HT3 and 5-HT4 receptors in the modulation of intestinal propulsion by luminal application of 5-HT and augmentation of endogenous 5-HT effects were studied in segments of guinea-pig ileum in vitro. Persistent propulsive contractions evoked by saline distension were examined using a modified Trendelenburg method. When 5-HT (30 nM, fluoxetine (selective serotonin reuptake inhibitor; 1 nM, 2-methyl-5-HT (5-HT3 receptor agonist; 1 mM or RS 67506 (5-HT4 receptor agonist, 1 µM was infused into the lumen, the pressure needed to initiate persistent propulsive activity fell significantly. A specific 5-HT4 receptor antagonist, SB 207266 (10 nM in lumen, abolished the effects of 5-HT, fluoxetine, and RS 67506, but not those of 2-methyl-5-HT. Granisetron (5-HT3 receptor antagonist; 1 µM in lumen abolished the effect of 5-HT, fluoxetine, RS 67506 and 2-methyl-5-HT. The NK3 receptor antagonist SR 142801 (100 nM in lumen blocked the effects of 5-HT, fluoxetine and 2-methyl-5-HT. SB 207266, granisetron and SR 142801 had no effect by themselves. Higher concentrations of fluoxetine (100 nM and 300 nM and RS 67506 (3 µM and 10 µM had no effect on the distension threshold for propulsive contractions. These results indicate that luminal application of exogenous 5-HT, or increased release of endogenous mucosal 5-HT above basal levels, acts to lower the threshold for propulsive contractions in the guinea-pig ileum via activation of 5-HT3 and 5-HT4 receptors and the release of tachykinins. The results further indicate that basal release of 5-HT is insufficient to alter the threshold for propulsive motor activity.

Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission.

Science.gov (United States)

Sengupta, Ayesha; Bocchio, Marco; Bannerman, David M; Sharp, Trevor; Capogna, Marco

2017-02-15

The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT 2A and 5-HT 1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT 1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders

Magnetic sensorless control of plasma position and shape in a tokamak

International Nuclear Information System (INIS)

Nakamura, K.; Luo, J.R.; Wang, H.Z.

2005-01-01

Magnetic sensorless sensing and control experiments of the plasma horizontal position have been carried out in the superconducting tokamak HT-7. The sensing is made focusing on the ripple frequency component of the power supply with thyristor and directly from them without time integration. There is no drift problem of integrator of magnetic sensors. Two kinds of control experiments were carried out, to keep the position constant and swing the position in a triangular waveform. And magnetic sensorless sensing of plasma shape is discussed. (author)

Effects of fuelling by using high-pressure supersonic molecular beam in the HL-1M tokamak

International Nuclear Information System (INIS)

Yao Lianghua; Feng Beibin; Feng Zhen; Dong Jiafu; Li Wenzhong; Xu Deming; Hong Wenyu

2002-01-01

Supersonic molecular beam (SMB), as a new fuelling method, has been successfully developed and used in HL-1M tokamak and HT-7 superconducting tokamak. The hydrogen clusters have been found in the beam produced by high working-gas pressure in recent experiments. With a penetration depth of hydrogen particles greater than 17 cm, the rate of increase of electron density for SMB injection, dn e -bar/dt, approaches that of the small ice pellet injection. The plasma density increases step by step after multi-pulse SMB injection, just as multi-pellet fuelling. Comparison of fuelling effects was made between SMB and ice pellet injection on the same shot of ohmic discharge in HL-1M

The Discharge Design of HL-2M with the Tokamak Simulation Code (TSC)

International Nuclear Information System (INIS)

Yudong Pan; Jardin, S.C.; Kes, C.

2007-01-01

We present results on the discharge design of the HL-2M tokamak, which is to be an upgrade to the existing HL-2A tokamak. We present simulation results for complete 5-sec. discharges, both double null and lower single null, for both ohmic and auxiliary heated discharges. We also discuss the vertical stability properties of the device

Different distributions of the 5-HT reuptake complex and the postsynaptic 5-HT(2A) receptors in Brodmann areas and brain hemispheres.

Science.gov (United States)

Rosel, Pilar; Arranz, Belén; Urretavizcaya, Mikel; Oros, Miguel; San, Luis; Vallejo, Julio; Navarro, Miguel Angel

2002-08-30

The aim of the present study was to determine the distribution of the presynaptic 5-HT reuptake complex and the 5-HT(2A) receptors through Brodmann areas from two control subjects, together with the possible existence of laterality between both brain hemispheres. A left laterality was observed in the postsynaptic 5-HT(2A) binding sites, with significantly higher B(max) values in the left frontal and cingulate cortex. In frontal cortex, [3H]imipramine and [3H]paroxetine binding showed the highest B(max) values in areas 25, 10 and 11. In cingulate cortex, the highest [3H]imipramine and [3H]paroxetine B(max) values were noted in Brodmann area 33 followed by area 24, while postsynaptic 5-HT(2A) receptors were mainly distributed through Brodmann areas 23 and 29. In temporal cortex, the highest [3H]imipramine and [3H]paroxetine B(max) was noted in Brodmann areas 28 and 34, followed by areas 35 and 38. All Brodmann areas from parietal cortex (1, 2, 3, 4, 5, 6, 7, 39, 40 and 43) showed similar presynaptic and postsynaptic binding values. In occipital cortex no differences were observed with regard to the brain hemisphere or to the Brodmann area (17, 18 and 19). These results suggest the need to carefully define the brain hemisphere and the Brodmann areas studied, as well to avoid comparisons between studies including different Brodmann areas or brain hemispheres.

5HT2A receptor blockade in dorsomedial striatum reduces repetitive behaviors in BTBR mice.

Science.gov (United States)

Amodeo, D A; Rivera, E; Cook, E H; Sweeney, J A; Ragozzino, M E

2017-03-01

Restricted and repetitive behaviors are a defining feature of autism, which can be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors. There is limited knowledge about the underlying neuropathophysiology contributing to these behaviors. Previous findings suggest that central 5HT 2A receptor activity is altered in autism, while recent work indicates that systemic 5HT 2A receptor antagonist treatment reduces repetitive behaviors in an idiopathic model of autism. 5HT 2A receptors are expressed in the orbitofrontal cortex and striatum. These two regions have been shown to be altered in autism. The present study investigated whether 5HT 2A receptor blockade in the dorsomedial striatum or orbitofrontal cortex in the BTBR mouse strain, an idiopathic model of autism, affects the phenotype related to restricted and repetitive behaviors. Microinfusion of the 5HT 2A receptor antagonist, M100907 into the dorsomedial striatum alleviated a reversal learning impairment and attenuated grooming behavior. M100907 infusion into the orbitofrontal cortex increased perseveration during reversal learning and potentiated grooming. These findings suggest that increased 5HT 2A receptor activity in the dorsomedial striatum may contribute to behavioral inflexibility and stereotyped behaviors in the BTBR mouse. 5HT 2A receptor signaling in the orbitofrontal cortex may be critical for inhibiting a previously learned response during reversal learning and expression of stereotyped behavior. The present results suggest which brain areas exhibit abnormalities underlying repetitive behaviors in an idiopathic mouse model of autism, as well as which brain areas systemic treatment with M100907 may principally act on in BTBR mice to attenuate repetitive behaviors. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

The role of the 5-HT2C receptor in emotional processing in healthy adults

OpenAIRE

2010-01-01

Serotonin (5-HT) has long been implicated in the pathophysiology of depression and anxiety, and the therapeutic effect of treatments. Several drugs useful in treatment produce either acute or neuroadaptive changes in 5-HT2C receptor activity, and there has been growing interest in how alterations in the 5-HT2C receptor might be important in mediating antidepressant and anxiolytic activity. The neuropsychological hypothesis of drug action implies that the clinical effects of medications a...

Paroxetine-induced reduction of sexual incentive motivation in female rats is not modified by 5-HT1B or 5-HT2C antagonists.

Science.gov (United States)

Kaspersen, Helge; Agmo, Anders

2012-03-01

Clinical data show that paroxetine causes sexual dysfunction in a substantial proportion of women taking this compound. This work was conducted to determine whether chronic paroxetine reduces sexual incentive motivation in female rats and whether this compound can modify any aspect of paced mating. The role of the 5-HT(1B) and 5-HT(2C) receptors in any potential effects was also evaluated. Ovariectomized female rats were implanted with osmotic minipumps releasing 10 mg/kg per day of paroxetine or vehicle for 28 days. Tests for sexual incentive motivation and paced mating were performed just before implantation and at regular intervals thereafter. The females were primed with estradiol benzoate (25 μg/rat) and progesterone (1 mg/rat) before each of these tests. On days 25-27 of treatment, the females were injected with the 5-HT(1B) antagonist GR125,743 (5 mg/kg), the 5-HT(2C) antagonist SB206,553 (5 mg/kg) and vehicle in counterbalanced order. Preinjection time was 30 min. Paroxetine reduced sexual incentive motivation on day 20 of treatment without affecting any aspect of paced mating. None of the antagonists modified the inhibitory effect of paroxetine on sexual incentive motivation. In the group chronically treated with vehicle, SB206,553 reduced proceptive behaviors in the paced mating test. No other effect was obtained. The effects of paroxetine seen in female rats are similar to those observed in women, suggesting that disturbances of sexual incentive motivation in rats are predictive of sexual dysfunction in women. The 5-HT(1B) and 5-HT(2C) receptors do not seem to be of any importance for paroxetine's inhibitory effect.

Radioligands for brain 5-HT{sub 2} receptor imaging in vivo: why do we need them?

Energy Technology Data Exchange (ETDEWEB)

Busatto, G.F. [Section of Clinical Neuropharmacology, Dept. of Psychological Medicine, Inst. of Psychiatry, London (United Kingdom)

1996-08-01

Recently, PET and SPET radiotracers with high specificity for 5-HT{sub 2} receptors have been developed. These have been studied in baboons and humans with promising results, displaying a binding profile compatible with the brain distribution of 5-HT{sub 2} receptors. It is predicted that studies with the newly developed 5-HT radioligands will substantially increase knowledge about the pharmacology of brain disorders. (orig./MG)

Multi-channel bolometer system on JFT-2M tokamak

International Nuclear Information System (INIS)

Tamai, Hiroshi; Maeno, Masaki; Matsuda, Toshiaki; Matoba, Tohru

1988-07-01

Multi-channel bolometer system is designed and installed to observe the radiation profile on JFT-2M tokamak. Sensor head is made of Thinistor, which is a kind of semiconductor, because it has the advantage of higher sensitivity of about one order of magnitude than the conventional metal foil bolometer and is suitable for the profile measurement in which the signal from the plasma is relatively small. The response and cooling characteristics of the bolometer sensor are suitable for the condition of JFT-2M tokamak plasma. Low noise circuit of bridge and differentiator is developed to optimize the signal to noise ratio in the JFT-2M operating condition. With use of the bolometer system, the radiation profile in joule heating plasma as well as additional heating plasma especially in H-mode plasma is successfully observed. (author)

Identification of a cys-ser substitution in the 5-HT{sub 2C} (HTR2C) receptor gene and allelic association to violent behavior and alcoholism

Energy Technology Data Exchange (ETDEWEB)

Lappalainen, J.; Ozaki, N.; Goldman, D. [National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (United States)] [and others

1994-09-01

Several lines of evidence suggest that brain serotonergic functions, including behavioral and neurochemical responses to 5-HT{sub 2C} agonist, are abnormal in some individuals with alcoholism and aggressive behaviors. The aim of the present study was to identify coding sequence variants in the human 5-HT{sub 2C} receptor gene which may cause abnormal or variant function of this receptor. Using SSCP analysis, a non-conservative cys-ser substitution was found in the 5-HT{sub 2C} receptor (designated 5-HT{sub 2Ccys} and 5-HT{sub 2Cser}). The polymorphism was typed in CEPH families to genetically map the gene. To test for association of the variant to alcoholism, violent behavior and serotonin function, the 5-HT{sub 2C} genotypes of 151 non-related Finnish male alcoholic violent offenders and impulsive fire setters and 127 Finnish psychiatrically interviewed healthy male volunteers were determined. CSF 5-HIAA concentrations were available for 74 alcoholic violent offenders and 25 healthy volunteers. Linkage analysis placed the 5-HT{sub 2C} gene on Xq21, a region that has been previously shown to contain genes for several mental retardation syndromes. The 5-HT{sub 2Ccys}/5-HT{sub 2Cser} genotype frequencies in alcoholic violent offenders and controls differed significantly (0.90/0.10 and 0.82/0.18, respectively, P=0.048). The association was found to be strongest in the violent offenders who did not fulfill the criteria for antisocial personality disorder (5-HT{sub 2Ccys}/5-HT{sub 2Cser} 0.93/0.07, p=0.021). No association was found between CSF 5-HIAA concentrations and 5-HT{sub 2C} genotype. These results implicate a 5-HT{sub 2C} receptor amino acid substitution in predisposition to alcohol abuse and violent behavior in a subgroup of alcoholics.

Tokamak

International Nuclear Information System (INIS)

Wesson, John.

1996-01-01

This book is the first compiled collection about tokamak. At first chapter tokamak is represented from fusion point of view and also the necessary conditions for producing power. The following chapters are represent plasma physics, the specifications of tokamak, plasma heating procedures and problems related to it, equilibrium, confinement, magnetohydrodynamic stability, instabilities, plasma material interaction, plasma measurement and experiments regarding to tokamak; an addendum is also given at the end of the book

The 5-HT2A receptor antagonist M100907 produces antiparkinsonian effects and decreases striatal glutamate

Directory of Open Access Journals (Sweden)

Twum eAnsah

2011-06-01

Full Text Available 5-HT plays a regulatory role in voluntary movements of the basal ganglia and have a major impact on disorders of the basal ganglia such as Parkinson’s disease (PD. Clinical studies have suggested that 5-HT2 receptor antagonists may be useful in the treatment of the motor symptoms of PD. We hypothesized that 5-HT2A receptor antagonists may restore motor function by regulating glutamatergic activity in the striatum. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP exhibited decreased performance on the beam-walking apparatus. Peripheral administration of the 5-HT2A receptor antagonist M100907 improved performance of MPTP-treated mice on the beam-walking apparatus. In vivo microdialysis revealed an increase in striatal extracellular glutamate in MPTP-treated mice and local perfusion of M100907 into the dorsal striatum significantly decreased extracellular glutamate levels in saline and MPTP-treated mice. Our studies suggest that blockade of 5-HT2A receptors may represent a novel therapeutic target for the motor symptoms of Parkinson’s disease.

Stationary Flowing Liquid Lithium (SFLiLi) systems for tokamaks

Science.gov (United States)

Zakharov, Leonid; Gentile, Charles; Roquemore, Lane

2013-10-01

The present approach to magnetic fusion which relies on high recycling plasma-wall interaction has exhausted itself at the level of TFTR, JET, JT-60 devices with no realistic path to the burning plasma. Instead, magnetic fusion needs a return to its original idea of insulation of the plasma from the wall, which was the dominant approach in the 1970s and upon implementations has a clear path to the DEMO device with PDT ~= 100 MW and Qelectric > 1 . The SFLiLi systems of this talk is the technology tool for implementation of the guiding idea of magnetic fusion. It utilizes the unique properties of flowing LiLi to pump plasma particles and, thus, insulate plasma from the walls. The necessary flow rate, ~= 1 g3/s, is very small, thus, making the use of lithium practical and consistent with safety requirements. The talk describes how chemical activity of LiLi, which is the major technology challenge of using LiLi in tokamaks, is addressed by SFLiLi systems at the level of already performed (HT-7) experiment, and in ongoing implementations for a prototype of SFLiLi for tokamak divertors and the mid-plane limiter for EAST tokamak (to be tested in the next experimental campaign). This work is supported by US DoE contract No. DE-AC02-09-CH11466.

Conduction-band valley spin splitting in single-layer H-T l2O

Science.gov (United States)

Ma, Yandong; Kou, Liangzhi; Du, Aijun; Huang, Baibiao; Dai, Ying; Heine, Thomas

2018-02-01

Despite numerous studies, coupled spin and valley physics is currently limited to two-dimensional (2D) transition-metal dichalcogenides (TMDCs). Here, we predict an exceptional 2D valleytronic material associated with the spin-valley coupling phenomena beyond 2D TMDCs—single-layer (SL) H-T l2O . It displays large valley spin splitting (VSS), significantly larger than that of 2D TMDCs, and a finite band gap, which are both critically attractive for the integration of valleytronics and spintronics. More importantly, in sharp contrast to all the experimentally confirmed 2D valleytronic materials, where the strong valence-band VSS (0.15-0.46 eV) supports the spin-valley coupling, the VSS in SL H-T l2O is pronounced in its conduction band (0.61 eV), but negligibly small in its valence band (21 meV), thus opening a way for manipulating the coupled spin and valley physics. Moreover, SL H-T l2O possesses extremely high carrier mobility, as large as 9.8 ×103c m2V-1s-1 .

First measurement of the magnetic turbulence induced Reynolds stress in a tokamak

International Nuclear Information System (INIS)

Xu Guosheng; Wan Baonian; Song Mei

2003-01-01

Reynolds stress component due to magnetic turbulence was first measured in the plasma edge region of the HT-7 superconducting tokamak using an insertable magnetic probe. A radial gradient of magnetic Reynolds stress was observed to be close to the velocity shear layer location; however, in this experiment its contribution to driving the poloidal flows is small compared to the electrostatic component. The electron heat transport driven by magnetic turbulence is quite small and cannot account for the total energy transport at the plasma edge

Transient snakes in an ohmic plasma associated with a minor disruption in the HT-7 Tokamak

Energy Technology Data Exchange (ETDEWEB)

Mao, Songtao; Xu, Liqing; Hu, Liqun; Chen, Kaiyun [Chinese Academy of Sciences, Hefei (China)

2014-05-15

A transient burst (∼2 ms, an order of the fast-particle slowdown timescale) of a spontaneous snake is observed for the first time in a HT-7 heavy impurity ohmic plasma. The features of the low-Z impurity snake are presented. The flatten electron profile due to the heavy impurity reveals the formation of a large magnetic island. The foot of the impurity accumulation is consistent with the location of the transient snake. The strong frequency-chirping behaviors and the spatial structures of the snake are also presented.

High performance discharges near the operational limit in HT-7

International Nuclear Information System (INIS)

Li Jiangang; Wan Baonian; Luo Jiarong; Gao Xiang; Zhao Yanping; Kuang Guangli; Zhang Xiaodong; Yang Yu; Yi Bao; Bojiang Ding; Jikang Xie; Yuanxi Wan

2001-01-01

Efforts have been made on the HT-7 tokamak to extend the stable operation boundaries. Extensive RF boronization and siliconization have been used and a wider operational Hugill diagram has been obtained. The transit density reached 1.3 times the Greenwald density limit in ohmic discharges. A stationary high performance discharge with q a =2.1 has been obtained after siliconization. Confinement improvement was obtained as a result of the significant reduction of electron thermal diffusivity χ e in the outer region of the plasma. An improved confinement phase was also observed with LHCD in the density range of 70-120% of the Greenwald density limit. Off-axis LH wave power deposition was attributed to the weak hollow current density profile. Code simulations and measurements showed good agreement with the off-axis LH wave deposition. Supersonic molecular beam injection has been successfully used to achieve stable high density operation in the region of the Greenwald density limit. (author)

Deficits in LTP induction by 5-HT2A receptor antagonist in a mouse model for fragile X syndrome.

Directory of Open Access Journals (Sweden)

Zhao-hui Xu

Full Text Available Fragile X syndrome is a common inherited form of mental retardation caused by the lack of fragile X mental retardation protein (FMRP because of Fmr1 gene silencing. Serotonin (5-HT is significantly increased in the null mutants of Drosophila Fmr1, and elevated 5-HT brain levels result in cognitive and behavioral deficits in human patients. The serotonin type 2A receptor (5-HT2AR is highly expressed in the cerebral cortex; it acts on pyramidal cells and GABAergic interneurons to modulate cortical functions. 5-HT2AR and FMRP both regulate synaptic plasticity. Therefore, the lack of FMRP may affect serotoninergic activity. In this study, we determined the involvement of FMRP in the 5-HT modulation of synaptic potentiation with the use of primary cortical neuron culture and brain slice recording. Pharmacological inhibition of 5-HT2AR by R-96544 or ketanserin facilitated long-term potentiation (LTP in the anterior cingulate cortex (ACC of WT mice. The prefrontal LTP induction was dependent on the activation of NMDARs and elevation of postsynaptic Ca(2+ concentrations. By contrast, inhibition of 5-HT2AR could not restore the induction of LTP in the ACC of Fmr1 knock-out mice. Furthermore, 5-HT2AR inhibition induced AMPA receptor GluR1 subtype surface insertion in the cultured ACC neurons of Fmr1 WT mice, however, GluR1 surface insertion by inhibition of 5-HT2AR was impaired in the neurons of Fmr1KO mice. These findings suggested that FMRP was involved in serotonin receptor signaling and contributed in GluR1 surface expression induced by 5-HT2AR inactivation.

Characterisation of 5-HT3C, 5-HT3D and 5-HT3E receptor subunits: evolution, distribution and function.

Science.gov (United States)

Holbrook, Joanna D; Gill, Catherine H; Zebda, Noureddine; Spencer, Jon P; Leyland, Rebecca; Rance, Kim H; Trinh, Han; Balmer, Gemma; Kelly, Fiona M; Yusaf, Shahnaz P; Courtenay, Nicola; Luck, Jane; Rhodes, Andrew; Modha, Sundip; Moore, Stephen E; Sanger, Gareth J; Gunthorpe, Martin J

2009-01-01

The 5-HT(3) receptor is a member of the 'Cys-loop' family of ligand-gated ion channels that mediate fast excitatory and inhibitory transmission in the nervous system. Current evidence points towards native 5-HT(3) receptors originating from homomeric assemblies of 5-HT(3A) or heteromeric assembly of 5-HT(3A) and 5-HT(3B). Novel genes encoding 5-HT(3C), 5-HT(3D), and 5-HT(3E) have recently been described but the functional importance of these proteins is unknown. In the present study, in silico analysis (confirmed by partial cloning) indicated that 5-HT(3C), 5-HT(3D), and 5-HT(3E) are not human-specific as previously reported: they are conserved in multiple mammalian species but are absent in rodents. Expression profiles of the novel human genes indicated high levels in the gastrointestinal tract but also in the brain, Dorsal Root Ganglion (DRG) and other tissues. Following the demonstration that these subunits are expressed at the cell membrane, the functional properties of the recombinant human subunits were investigated using patch clamp electrophysiology. 5-HT(3C), 5-HT(3D), and 5-HT(3E) were all non-functional when expressed alone. Co-transfection studies to determine potential novel heteromeric receptor interactions with 5-HT(3A) demonstrated that the expression or function of the receptor was modified by 5-HT(3C) and 5-HT(3E), but not 5-HT(3D). The lack of distinct effects on current rectification, kinetics or pharmacology of 5-HT(3A) receptors does not however provide unequivocal evidence to support a direct contribution of 5-HT(3C) or 5-HT(3E) to the lining of the ion channel pore of novel heteromeric receptors. The functional and pharmacological contributions of these novel subunits to human biology and diseases such as irritable bowel syndrome for which 5-HT(3) receptor antagonists have major clinical usage, therefore remains to be fully determined.

HTO/HT discriminating samplers constructed for the french experiment on the environmental behaviour of HT

International Nuclear Information System (INIS)

Ogram, G.L.

1988-12-01

The French Experiment on Environmental Tritium Behaviour was a field experiment carried out to determine the rate of formation of atmospheric HTO from a release of HT to the natural environment. The Canadian Fusion Fuels Technology Project and Ontario Hydro contributed to the project by supplying HTO/HT-discriminating, atmospheric tritium samplers. Each sampler consisted of a molecular-sieve trap to capture HTO followed by a Pd-impregnated molecular-sieve trap to oxidise and collect HT from the same air stream. This method was selected as it provided high sensitivity over short sampling periods and was convenient for field use. Laboratory tests indicated that this system measured HT concentrations reliably, but only achieved limited discrimination between HT and HTO at HTO/HT concentration ratios below 10 -2 to 10 -3 . Small cold traps were therefore operated during the French experiment in addition to the molecular-sieve samplers exhibited much improved discrimination in the field (approaching 10 4 ), possibly due to higher sampling flow rates than used in the laboratory. These results demonstrate that care should be taken in using desiccant-based, HTO/HT-discriminating samplers when the HT concentration is much higher than HTO concentration, and suggest the need to systematically characterize and perhaps improve the performance of discriminating samplers at low HTO/HT ratios

MDMA Increases Excitability in the Dentate Gyrus: Role of 5HT2A Receptor Induced PGE2 Signaling

Science.gov (United States)

Collins, Stuart A.; Huff, Courtney; Chiaia, Nicolas; Gudelsky, Gary A.; Yamamoto, Bryan K.

2015-01-01

MDMA is a widely abused psychostimulant which causes release of serotonin in various forebrain regions. Recently, we reported that MDMA increases extracellular glutamate concentrations in the dentate gyrus, via activation of 5HT2A receptors. We examined the role of prostaglandin signaling in mediating the effects of 5HT2A receptor activation on the increases in extracellular glutamate and the subsequent long-term loss of parvalbumin interneurons in the dentate gyrus caused by MDMA. Administration of MDMA into the dentate gyrus of rats increased PGE2 concentrations which was prevented by coadministration of MDL100907, a 5HT2A receptor antagonist. MDMA-induced increases in extracellular glutamate were inhibited by local administration of SC-51089, an inhibitor of the EP1 prostaglandin receptor. Systemic administration of SC-51089 during injections of MDMA prevented the decreases in parvalbumin interneurons observed 10 days later. The loss of parvalbumin immunoreactivity after MDMA exposure coincided with a decrease in paired-pulse inhibition and afterdischarge threshold in the dentate gyrus. These changes were prevented by inhibition of EP1 and 5HT2A receptors during MDMA. Additional experiments revealed an increased susceptibility to kainic acid-induced seizures in MDMA treated rats which could be prevented with SC51089 treatments during MDMA exposure. Overall, these findings suggest that 5HT2A receptors mediate MDMA-induced PGE2 signaling and subsequent increases in glutamate. This signaling mediates parvalbumin cell losses as well as physiologic changes in the dentate gyrus, suggesting that the lack of the inhibition provided by these neurons increases the excitability within the dentate gyrus of MDMA treated rats. PMID:26670377

A discussion on practicable scheme for machine control system of HL-2A tokamak

International Nuclear Information System (INIS)

Li Qiang; Song Xianming; Jiang Chao

2001-01-01

This is the modified version of The Preliminary Design on the Hardware and Nets of HL-2A Tokamak. In this version, centralized control as well as the field bus communication on HL-2A Tokamak is used. The hardware components and the operational theory are introduced. The questions of practice program, extensibility, centralized control, cooperation with other subsystems and the continuous adaptation of present device are all discussed. The budget of the system is detailed. To keep the step with the overall engineering constructions of HL-2A, suggestions of the time program are presented for the system design, instrument purchases, installation, construction, user program development and the final operation processes for the machine control system of HL-2A Tokamak

Development of a Fast Valve for Disruption Mitigation and its Preliminary Application to EAST and HT-7

International Nuclear Information System (INIS)

Zhuang Huidong; Zhang Xiaodong

2013-01-01

In large tokamaks, disruption of high current plasma would damage plasma facing component surfaces (PFCs) or other inner components due to high heat load, electromagnetic force load and runaway electrons. It would also influence the subsequent plasma discharge due to production of impurities during disruptions. So the avoidance and mitigation of disruptions is essential for the next generation of tokamaks, such as ITER. Massive gas injection (MGI) is a promising method of disruption mitigation. A new fast valve has been developed successfully on EAST. The valve can be opened in 0.5 ms, and the duration of open state is largely dependent on the gas pressure and capacitor voltage. The throughput of the valve can be adjusted from 0 mbar·L to 700 mbar·L by changing the capacitor voltage and gas pressure. The response time and throughput of the fast valve can meet the requirement of disruption mitigation on EAST. In the last round campaign of EAST and HT-7 in 2010, the fast valve has operated successfully. He and Ar was used for the disruption mitigation on HT-7. By injecting the proper amount of gas, the current quench rate could be slowed down, and the impurities radiation would be greatly improved. In elongated plasmas of EAST discharges, the experimental data is opposite to that which is expected. (magnetically confined plasma)

Contribution of 5-HT2A receptors on diaphragmatic recovery after chronic cervical spinal cord injury.

Science.gov (United States)

Lee, Kun-Ze; Gonzalez-Rothi, Elisa J

2017-10-01

Unilateral C2 spinal cord hemisection (C2Hx) interrupts bulbospinal respiratory pathways innervating ipsilateral phrenic motoneurons, resulting in cessation of ipsilateral diaphragm motor output. Plasticity within the spinal neural circuitry controlling the diaphragm can induce partial recovery of phrenic bursting which correlates with the time-dependent return of spinal serotonin (5-HT) immunoreactivity in the vicinity of phrenic motoneurons. The 5-HT 2A receptor subtype is present on phrenic motoneurons and its expression is up-regulated after cervical spinal cord injury; however the functional role of these receptors following injury has not been clearly defined. The present study evaluated the functional role of 5-HT 2A receptors by testing the hypothesis that pharmacologic blockade would attenuate diaphragm activity in rats with chronic cervical spinal cord injury. Bilateral diaphragm electromyography (EMG) was performed in vagal-intact and spontaneously breathing rats before and after intravenous administration of the 5-HT 2A receptor antagonist Ketanserin (1mg/kg). Intravenous ketanserin significantly attenuated ipsilateral diaphragm EMG activity in C2Hx animals but had no impact on diaphragm output in uninjured animals. We conclude that 5-HT 2A receptor activation contributes to the recovery of ipsilateral phrenic motor output after chronic cervical spinal cord injury. Copyright © 2017 Elsevier B.V. All rights reserved.

5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease

OpenAIRE

Ferguson, Marcus C.; Nayyar, Tultul; Deutch, Ariel Y.; Ansah, Twum A.

2010-01-01

Clinical observations have suggested that ritanserin, a 5-HT2A/C receptor antagonist may reduce motor deficits in persons with Parkinson's Disease (PD). To better understand the potential antiparkinsonian actions of ritanserin, we compared the effects of ritanserin with the selective 5-HT2A receptor antagonist M100907 and the selective 5-HT2C receptor antagonist SB 206553 on motor impairments in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP-treated mice exhibited...

5-HT2C receptor involvement in the control of persistence in the reinforced spatial alternation animal model of obsessive-compulsive disorder.

Science.gov (United States)

Papakosta, Vassiliki-Maria; Kalogerakou, Stamatina; Kontis, Dimitris; Anyfandi, Eleni; Theochari, Eirini; Boulougouris, Vasileios; Papadopoulos, Sokrates; Panagis, George; Tsaltas, Eleftheria

2013-04-15

The serotonergic system is implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, the distinct role of serotonin (5-HT) receptor subtypes remains unclear. This study investigates the contribution of 5-HT2A and 5-HT2C receptors in the modulation of persistence in the reinforced spatial alternation model of OCD. Male Wistar rats were assessed for spontaneous and pharmacologically induced (by m-chlorophenylpiperazine: mCPP) directional persistence in the reinforced alternation OCD model. Systemic administration of mCPP (non-specific 5-HT agonist, 2.5mg/kg), M100907 (selective 5-HT2A receptor antagonist, 0.08 mg/kg), SB242084 (selective 5-HT2C receptor antagonist, 0.5 mg/kg) and vehicle was used. Experiment 1 investigated M100907 and SB242084 effects in animals spontaneously exhibiting high and low persistence during the early stages of alternation training. Experiment 2 investigated M100900 and SB242084 effects on mCPP-induced persistence. Under the regime used in Experiment 1, 5-HT2A or 5-HT2C receptor antagonism did not affect spontaneous directional persistence in either high or low persistence groups. In Experiment 2, 5-HT2C but not 5-HT2A receptor antagonism significantly reduced, but did not abolish, mCPP-induced directional persistence. These findings suggest that 5-HT2C but not 5-HT2A receptors contribute to the modulation of mCPP-induced persistent behaviour, raising the possibility that the use of 5-HT2C antagonists may have a therapeutic value in OCD. Copyright © 2013 Elsevier B.V. All rights reserved.

Fabrication of P3HT/gold nanoparticle LB films by P3HT templating Langmuir monolayer

International Nuclear Information System (INIS)

Chen, Liang-Huei; Hsu, Wen-Ping; Chan, Han-Wen; Lee, Yuh-Lang

2014-01-01

Highlights: • Addition of ODA into the P3HT monolayer can significantly improve the dispersion ability of P3HT molecules. • The adsorption ability of the P3HT monolayer to the dispersed AuNPs can also be enhanced by the presence of ODA. - Abstract: Regioregular poly(3-hexyl thiophene) (rr-P3HT) and mixed P3HT/octadecyl amine (ODA) were used as template monolayers to adsorb the gold nanoparticles (AuNPs) dispersed in subphase. The behaviors of P3HT and P3HT/ODA monolayers were investigated by surface pressure area per molecule (π–A) isotherms, transmission electron microscopy (TEM) and atomic force microscopy (AFM). The experimental results show that P3HT does not form a homogeneous film and tends to aggregate at the air/water interface. Meanwhile, the amount of AuNPs adsorbed by the P3HT monolayers is low, attributable to the weak interaction between AuNPs and P3HT. By introduction of ODA molecules into the P3HT monolayer, the spreading of P3HT molecules at the air/water interface is improved and the aggregation of P3HT is significantly inhibited. A nearly uniform and homogeneously mixed P3HT/ODA monolayer can be obtained when 50% of ODA is introduced. It is also found that the introduction of ODA can significantly increase the adsorption of AuNPs. For the mixed monolayer with low ratio of ODA (P3HT/ODA = 1/0.2), a higher concentration of adsorbed AuNPs was observed on the corresponding monolayer. However, when the ODA/P3HT ratio increases to 1/1, the AuNPs tend to form three-dimensional (3D) aggregates and the AuNPs cannot distribute well as a homogeneous monolayer. This result is ascribed to the increasing hydrophobicity of the adsorbed AuNPs because of capping of more ODA molecules

Intrahippocampal LSD accelerates learning and desensitizes the 5-HT(2A) receptor in the rabbit, Romano et al.

Science.gov (United States)

Romano, Anthony G; Quinn, Jennifer L; Li, Luchuan; Dave, Kuldip D; Schindler, Emmanuelle A; Aloyo, Vincent J; Harvey, John A

2010-10-01

Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT(2A) receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT(2A)-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning. This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine elicit the 5-HT(2A)-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning. LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD, DOI was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT(2A) receptor as measured by a decrease in DOI-elicited head bobs. Acute parenteral or intrahippocampal LSD elicited a 5-HT(2A) but not a 5-HT(2C)-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nmol per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls. LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT(2A) receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT(2A) receptor within the hippocampus as a result of repeated administration of its agonist (LSD).

Convergent [18]F-labeling and evaluation of N-benzyl-phenethylamines as 5-HT2A receptor PET ligands

DEFF Research Database (Denmark)

Petersen, Ida Nymann; Villadsen, Jonas; Hansen, Hanne Demant

2016-01-01

Positron emission tomography (PET) investigations of the 5-HT2A receptor (5-HT2AR) system can be used as a research tool in diseases such as depression, Alzheimer's disease and schizophrenia. We have previously developed a (11)C-labeled agonist PET ligand ([(11)C]Cimbi-36), and the aim of this st......Positron emission tomography (PET) investigations of the 5-HT2A receptor (5-HT2AR) system can be used as a research tool in diseases such as depression, Alzheimer's disease and schizophrenia. We have previously developed a (11)C-labeled agonist PET ligand ([(11)C]Cimbi-36), and the aim...... of this study was to identify a (18)F-labeled analogue of this PET-ligand. Thus, we developed a convergent radiochemical approach giving easy access to 5 different (18)F-labeled ligands structurally related to Cimbi-36 from a common (18)F-labeled intermediate. After intravenous injection, all ligands entered...... the pig brain. However, since within-scan intervention with ketanserin, a known orthosteric 5-HT2A receptor antagonist, did not result in significant blocking, the radioligands seem unsuitable for neuroimaging of the 5-HT2AR in vivo....

Numerical study for determining PF coil system parameters in MHD equilibrium of KT-2 tokamak plasma

International Nuclear Information System (INIS)

Ryu, J.; Hong, S.H.; Lee, K.W.; Hong, B.G.; In, S.R.; Kim, S.K.

1995-01-01

The KT-2 is a large-aspect-ratio medium-sized divertor tokamak in the conceptual design phase and planned to be operational in 1998 at the Korea Atomic Energy Research Institute (KAERI). Plasma equilibrium in tokamak can be acquired by controlling the current of poloidal field (PF) coils in appropriate geometries and positions. In this study, the authors have performed numerical calculations to achieve the various equilibrium conditions fitting given plasma shapes and satisfying PF current limitations. Usually an ideal magnetohydrodynamic (MHD) equation is used to obtain the equilibrium solution of tokamak plasma, and it is practical to take advantage of a numerical method in solving the MHD equation because it has nonlinear source terms. Two equilibrium codes have been applied to find a double-null configuration of free-boundary tokamak plasma in KT-2: one is of the authors' own developing and the other is a free-boundary tokamak equilibrium code (FBT) that has been used mainly for the verification of developed code's results. PF coil system parameters including their positions and currents are determined for the optimization of input power required when the specifications of KT-2 tokamak are met. Then, several sets of equilibrium conditions during the tokamak operation are found to observe the changes of poloidal field currents with the passing of operation time step, and the basic stability problems related with the magnetic field structure is also considered

Actions of alpha2 adrenoceptor ligands at alpha2A and 5-HT1A receptors: the antagonist, atipamezole, and the agonist, dexmedetomidine, are highly selective for alpha2A adrenoceptors.

Science.gov (United States)

Newman-Tancredi, A; Nicolas, J P; Audinot, V; Gavaudan, S; Verrièle, L; Touzard, M; Chaput, C; Richard, N; Millan, M J

1998-08-01

This study examined the activity of chemically diverse alpha2 adrenoceptor ligands at recombinant human (h) and native rat (r) alpha2A adrenoceptors compared with 5-HT1A receptors. First, in competition binding experiments at h alpha2A and h5-HT1A receptors expressed in CHO cells, several compounds, including the antagonists 1-(2-pyrimidinyl)piperazine (1-PP), (+/-)-idazoxan, benalfocin (SKF 86466), yohimbine and RX 821,002, displayed preference for h alpha2A versus h5-HT1A receptors of only 1.4-, 3.6-, 4-, 10- and 11-fold, respectively (based on differences in pKi values). Clonidine, brimonidine (UK 14304), the benzopyrrolidine fluparoxan and the guanidines guanfacine and guanabenz exhibited intermediate selectivity (22- to 31-fold) for h alpha2A receptors. Only the antagonist atipamezole and the agonist dexmedetomidine (DMT) displayed high preference for alpha2 adrenoceptors (1290- and 91-fold, respectively). Second, the compounds were tested for their ability to induce h5-HT1A receptor-mediated G-protein activation, as indicated by the stimulation of [35S]GTPgammaS binding. All except atipamezole and RX 821,002 exhibited agonist activity, with potencies which correlated with their affinity for h5-HT1A receptors. Relative efficacies (Emax values) were 25-35% for guanabenz, guanfacine, WB 4101 and benalfocin, 50-65% for 1-PP, (+/-)-idazoxan and clonidine, and over 70% for fluparoxan, oxymetazoline and yohimbine (relative to 5-HT = 100%). Yohimbine-induced [35S]GTPgammaS binding was inhibited by the selective 5-HT1A receptor antagonist WAY 100,635. In contrast, RX 821,002 was the only ligand which exhibited antagonist activity at h5-HT1A receptors, inhibiting 5-HT-stimulated [35S]GTPgammaS binding. Atipamezole, which exhibited negligeable affinity for 5-HT1A receptors, was inactive. Third, the affinities for r alpha2A differed considerably from the affinities for h alpha2A receptors whereas the affinities for r5-HT1A differed much less from the affinities for h5-HT

Burning plasma simulation and environmental assessment of tokamak, spherical tokamak and helical reactors

International Nuclear Information System (INIS)

Yamazaki, K.; Uemura, S.; Oishi, T.; Arimoto, H.; Shoji, T.; Garcia, J.

2009-01-01

Reference 1-GWe DT reactors (tokamak TR-1, spherical tokamak ST-1 and helical HR-1 reactors) are designed using physics, engineering and cost (PEC) code, and their plasma behaviours with internal transport barrier operations are analysed using toroidal transport analysis linkage (TOTAL) code, which clarifies the requirement of deep penetration of pellet fuelling to realize steady-state advanced burning operation. In addition, economical and environmental assessments were performed using extended PEC code, which shows the advantage of high beta tokamak reactors in the cost of electricity (COE) and the advantage of compact spherical tokamak in life-cycle CO 2 emission reduction. Comparing with other electric power generation systems, the COE of the fusion reactor is higher than that of the fission reactor, but on the same level as the oil thermal power system. CO 2 reduction can be achieved in fusion reactors the same as in the fission reactor. The energy payback ratio of the high-beta tokamak reactor TR-1 could be higher than that of other systems including the fission reactor.

ICRF heating experiments in JFT-2 tokamak

International Nuclear Information System (INIS)

Matsumoto, Hiroshi

1986-01-01

This is an experimental study of ICRF heating on JFT-2 Tokamak in Japan Atomic Energy Research Institute. In this study, we first clarified physical and engineering problems of ICRF heating of tokamak plasma. Next, we optimized the design of the ICRF heating system, and the plasma parameters for the heating. Finally, we could demonstrate a high efficiency of this additional heating method by launching RF power which is two or three times as large as an ohmic input power to a plasma. And we achieved following things. (1) We optimized a design of an antenna, and we improved a durability of the system for high voltage. With the result that we achieved the maximum power density on an antenna. (2) We demonstrated that electron heating regime and ion heating regime can be easily accessed by controlling plasma parameters. Also we found the optimum heating conditions in each heating regime. (3) We experimentally clarified the production mechanism of impurities during ICRF heating. We could reduce the influx of metal impurity ions to a plasma by employing low z materials for limiters and antenna shields. Consequently, we improved a heating efficiency of electrons. Next, we studied a power balance of plasma during ICRF heating, and we could compare heating characteristics of ICRF with other additional heatings on JFT-2. (author)

Structure-activity relationships of constrained phenylethylamine ligands for the serotonin 5-ht2 receptors

DEFF Research Database (Denmark)

Isberg, Vignir; Paine, James; Leth-Petersen, Sebastian

2013-01-01

Serotonergic ligands have proven effective drugs in the treatment of migraine, pain, obesity, and a wide range of psychiatric and neurological disorders. There is a clinical need for more highly 5-HT2 receptor subtype-selective ligands and the most attention has been given to the phenethylamine...... about the bioactive conformation of the amine functionality. However, combined 1,2-constriction by cyclization has only been tested with one compound. Here, we present three new 1,2-cyclized phenylethylamines, 9-11, and describe their synthetic routes. Ligand docking in the 5-HT2B crystal structure...... but shift the placement of the core scaffold. The constraints in 9-11 resulted in docking poses with the 4-bromine in closer vicinity to 5.46, which is polar only in the human 5-HT2A subtype, for which 9-11 have the lowest affinity. The new ligands, conformational analysis and docking expand the structure...

Apollo-L2, an advanced fuel tokamak reactor utilizing direct conversion

International Nuclear Information System (INIS)

Emmert, G.A.; Kulcinski, G.L.; Blanchard, J.P.; El-Guebaly, L.A.; Khater, H.Y.; Santarius, J.F.; Sawan, M.E.; Sviatoslavsky, I.N.; Wittenberg, L.J.; Witt, R.J.

1989-01-01

A scoping study of a tokamak reactor fueled by a D- 3 He plasma is presented. The Apollo D- 3 He tokamak capitalizes on recent advances in high field magnets (20 T) and utilizes rectennas to convert the synchrotron radiation directly to electricity. The low neutron wall loading (0.1 MW/m 2 ) permits a first wall lasting the life of the plant and enables the reactor to be classified as inherently safe. The cost of electricity is less than that from a similar power level DT reactor. 10 refs., 1 fig., 4 tabs

Central Serotonin-2A (5-HT2A Receptor Dysfunction in Depression and Epilepsy: The Missing Link?

Directory of Open Access Journals (Sweden)

Bruno Pierre Guiard

2015-03-01

Full Text Available 5-Hydroxytryptamine 2A receptors (5-HT2A-Rs are G-protein coupled receptors. In agreement with their location in the brain, they have been implicated not only in various central physiological functions including memory, sleep, nociception, eating and reward behaviors, but also in many neuropsychiatric disorders. Interestingly, a bidirectional link between depression and epilepsy is suspected since patients with depression and especially suicide attempters have an increased seizure risk, while a significant percentage of epileptic patients suffer from depression. Such epidemiological data led us to hypothesize that both pathologies may share common anatomical and neurobiological alteration of the 5-HT2A signaling. After a brief presentation of the pharmacological properties of the 5-HT2A-Rs, this review illustrates how these receptors may directly or indirectly control neuronal excitability in most networks involved in depression and epilepsy through interactions with the monoaminergic, GABAergic and glutamatergic neurotransmissions. It also synthetizes the preclinical and clinical evidence demonstrating the role of these receptors in antidepressant and antiepileptic responses.

Radiosynthesis, evaluation and preclinical studies of a new 5HT2A radioligand

International Nuclear Information System (INIS)

Mertens, J.; Terriere, D.; Baeken, C.; D'Haenan, H.; Flamen, P.; Bossuyt, A.; Leysen, J.

1998-01-01

123 I-5-I-R91150, a radioiodinated analogue of R91150 (a ligand (antagonist) of Janssen Research Foundation), showing high affinity and selectivity for 5HT 2A receptors, was developed as a potential in vivo 5HT 2A receptor tracer for SPECT. The applied radiochemistry, whereby the radioiodine was substituted on the 5 - position of the benzamide ring, allowed to obtain the tracer with high specific activity and high purity. In vitro and in vivo rat studies revealed that the new tracer bound reversibly with the required high affinity (Kd=0.1 nM) and high selectivity (a factor ranging from 10000 to at least 50 vis a vis other receptors) to 5HT 2A receptors. In young normal subjects the major part of the 123 I-5-I-R91150 radioactivity in the brain is present in cortical areas. Cortical area to cerebellum activity ratio reaches an equilibrium value of about 1.8 around 90 min. till 4 hours p.i.. This binding was specific and reversible. The cortical activity reflects a distribution in the brain similar to that of the mapping of 5HT 2A receptors from post mortem studies. These findings suggested that 123 I-5-I-R91150 allows imaging and quantitative estimation with SPECT and could be used for further clinical studies. The radiobromine analogue was synthetised as a potential PET tracer. (author)

Serotonin mediation of early memory formation via 5HT2B receptor-induced glycogenolysis in the day-old chick

Directory of Open Access Journals (Sweden)

Marie Elizabeth Gibbs

2014-04-01

Full Text Available Investigation of the effects of serotonin on memory formation in the chick revealed an action on at least two 5HT receptors. Serotonin injected intracerebrally produced a biphasic effect on memory consolidation with enhancement at low doses and inhibition at higher doses. The non-selective 5HT receptor antagonist methiothepin and the selective 5HT2B/C receptor antagonist SB221284 both inhibited memory, suggesting actions of serotonin on at least 2 different receptor subtypes. The 5HT2B/C and astrocyte-specific 5-HT receptor agonists, fluoxetine and paroxetine, enhanced memory and the effect was attributed to glycogenolysis. Inhibition of glycogenolysis with a low dose of DAB prevented both serotonin and fluoxetine from enhancing memory during short-term memory but not during intermediate memory. The role of serotonin on the 5HT2B/C receptor appears to involve glycogen breakdown in astrocytes during short-term memory, whereas other published evidence attributes the second period of glycogenolysis to noradrenaline.

Synthesis and in vivo evaluation of [O-methyl-11C](2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine as a 5-HT2A receptor PET ligand

International Nuclear Information System (INIS)

Kumar, J.S. Dileep; Prabhakaran, Jaya; Erlandsson, Kjell; Majo, Vattoly J.; Simpson, Norman R.; Pratap, Mali; Heertum, Ronald L. van; Mann, J. John; Parsey, Ramin V.

2006-01-01

The serotonin 2A (5-HT 2A ) receptor is implicated in the pathophysiology of schizophrenia and mood disorders, and in vivo studies of this receptor would be of value in studying the pathophysiology of these disorders and in measuring the relationship of clinical response to receptor occupancy for 5-HT 2A antagonists such as atypical antipsychotics. Therefore, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)-phenyl]ethyl] phenoxy]ethyl-1-methylpyrrolidine (MPM) (13), a selective and high-affinity (K i =0.79 nM) 5HT 2A antagonist, has been radiolabeled with carbon-11 by O-methylation of the corresponding desmethyl analogue (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-hydroxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine (12) with [ 11 C]methyltriflate in order to determine the suitability of [ 11 C]MPM to quantify 5-HT 2A in living brain using PET. Desmethyl-MPM 12 and standard MPM were prepared, starting from 3-hydroxymethylphenol (2), in excellent yield. The yield obtained for radiolabeling was 40±5% (EOB), and the total synthesis time was 30 min at EOS. PET studies with [ 11 C]MPM in baboon showed a distribution in the brain consistent with the known distribution of 5-HT 2A receptors. The time-activity curves for the high-binding regions peaked at ∼45 min after injection. Blocking studies with M100907 demonstrated not only 38-57% blocking of tracer binding in brain regions known to have 5-HT 2A receptors but also 38% blocking in cerebellum, which has a low 5-HT 2A receptor concentration. Although [ 11 C]MPM exhibits appropriate kinetics in baboon for imaging 5-HT 2A receptors, its specific binding in cerebellum and higher proportion of nonspecific binding limit its usefulness for the in vivo quantification of 5-HT 2A receptors with PET

Serotonin hyperinnervation and upregulated 5-HT2A receptor expression and motor-stimulating function in nigrostriatal dopamine-deficient Pitx3 mutant mice.

Science.gov (United States)

Li, Li; Qiu, Guozhen; Ding, Shengyuan; Zhou, Fu-Ming

2013-01-23

The striatum receives serotonin (5-hydroxytryptamine, 5-HT) innervation and expresses 5-HT2A receptors (5-HT2ARs) and other 5-HT receptors, raising the possibility that the striatal 5-HT system may undergo adaptive changes after chronic severe dopamine (DA) loss and contribute to the function and dysfunction of the striatum. Here we show that in transcription factor Pitx3 gene mutant mice with a selective, severe DA loss in the dorsal striatum mimicking the DA denervation in late Parkinson's disease (PD), both the 5-HT innervation and the 5-HT2AR mRNA expression were increased in the dorsal striatum. Functionally, while having no detectable motor effect in wild type mice, the 5-HT2R agonist 2,5-dimethoxy-4-iodoamphetamine increased both the baseline and l-dopa-induced normal ambulatory and dyskinetic movements in Pitx3 mutant mice, whereas the selective 5-HT2AR blocker volinanserin had the opposite effects. These results demonstrate that Pitx3 mutant mice are a convenient and valid mouse model to study the compensatory 5-HT upregulation following the loss of the nigrostriatal DA projection and that the upregulated 5-HT2AR function in the DA deficient dorsal striatum may enhance both normal and dyskinetic movements. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of genetic and pharmacological blockade of GABA receptors on the 5-HT2C receptor function during stress.

OpenAIRE

Martin Cédric B P; Gassmann Martin; Chevarin Caroline; Hamon Michel; Rudolph Uwe; Bettler Bernhard; Lanfumey Laurence; Mongeau Raymond

2014-01-01

5-HT2C receptors play a role in psychoaffective disorders and often contribute to the antidepressant and anxiolytic effects of psychotropic drugs. During stress, activation of these receptors exerts a negative feedback on serotonin (5-HT) release, probably by increasing the activity of GABAergic interneurons. However, to date, the GABA receptor types that mediate the 5-HT2C receptor-induced feedback inhibition are still unknown. To address this question, we assessed the inhibition of 5-HT tur...

Application of PLC timing control in the neutral beam injector of HT-7

International Nuclear Information System (INIS)

Song Shihua; Liu Zhimin; Liu Sheng; Hu Chundong

2006-01-01

HT-7 tokamak high power Neutral Beam Injector heating system runs in the mode of pulse timing-control of PLC. The thesis discusses the theory about the operation for the experiment of discharge, which is controlled by PLC logical connection and introduces excellent user-friendly operating interface and the development of the ladder application program and upper monitor program in the VB6.0 environment. Monitor the conditions of power and facility real time by the upper monitor interface. The application of PLC control system ensures the experiment facility running safely and convenient for modifying and setting the parameter simply during the course of experiment. (authors)

Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling.

Science.gov (United States)

Buchborn, Tobias; Schröder, Helmut; Höllt, Volker; Grecksch, Gisela

2014-06-01

A re-balance of postsynaptic serotonin (5-HT) receptor signalling, with an increase in 5-HT1A and a decrease in 5-HT2A signalling, is a final common pathway multiple antidepressants share. Given that the 5-HT1A/2A agonist lysergic acid diethylamide (LSD), when repeatedly applied, selectively downregulates 5-HT2A, but not 5-HT1A receptors, one might expect LSD to similarly re-balance the postsynaptic 5-HT signalling. Challenging this idea, we use an animal model of depression specifically responding to repeated antidepressant treatment (olfactory bulbectomy), and test the antidepressant-like properties of repeated LSD treatment (0.13 mg/kg/d, 11 d). In line with former findings, we observe that bulbectomised rats show marked deficits in active avoidance learning. These deficits, similarly as we earlier noted with imipramine, are largely reversed by repeated LSD administration. Additionally, bulbectomised rats exhibit distinct anomalies of monoamine receptor signalling in hippocampus and/or frontal cortex; from these, only the hippocampal decrease in 5-HT2 related [(35)S]-GTP-gamma-S binding is normalised by LSD. Importantly, the sham-operated rats do not profit from LSD, and exhibit reduced hippocampal 5-HT2 signalling. As behavioural deficits after bulbectomy respond to agents classified as antidepressants only, we conclude that the effect of LSD in this model can be considered antidepressant-like, and discuss it in terms of a re-balance of hippocampal 5-HT2/5-HT1A signalling. © The Author(s) 2014.

Continuous tokamaks

International Nuclear Information System (INIS)

Peng, Y.K.M.

1978-04-01

A tokamak configuration is proposed that permits the rapid replacement of a plasma discharge in a ''burn'' chamber by another one in a time scale much shorter than the elementary thermal time constant of the chamber first wall. With respect to the chamber, the effective duty cycle factor can thus be made arbitrarily close to unity minimizing the cyclic thermal stress in the first wall. At least one plasma discharge always exists in the new tokamak configuration, hence, a continuous tokamak. By incorporating adiabatic toroidal compression, configurations of continuous tokamak compressors are introduced. To operate continuous tokamaks, it is necessary to introduce the concept of mixed poloidal field coils, which spatially groups all the poloidal field coils into three sets, all contributing simultaneously to inducing the plasma current and maintaining the proper plasma shape and position. Preliminary numerical calculations of axisymmetric MHD equilibria in continuous tokamaks indicate the feasibility of their continued plasma operation. Advanced concepts of continuous tokamaks to reduce the topological complexity and to allow the burn plasma aspect ratio to decrease for increased beta are then suggested

Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor

Science.gov (United States)

Walterscheid, Jeffrey P.; Nghiem, Dat X.; Kazimi, Nasser; Nutt, Leta K.; McConkey, David J.; Norval, Mary; Ullrich, Stephen E.

2006-01-01

Exposure to UV radiation induces skin cancer and suppresses the immune response. To induce immune suppression, the electromagnetic energy of UV radiation must be absorbed by an epidermal photoreceptor and converted into a biologically recognizable signal. Two photoreceptors have been recognized: DNA and trans-urocanic acid (UCA). Trans-UCA is normally found in the outermost layer of skin and isomerizes to the cis isomer upon exposure to UV radiation. Although UCA was identified as a UV photoreceptor years ago, and many have documented its ability to induce immune suppression, its exact mode of action remains elusive. Particularly vexing has been the identity of the molecular pathway by which cis-UCA mediates immune suppression. Here we provide evidence that cis-UCA binds to the serotonin [5-hydroxytryptamine (5-HT)] receptor with relatively high affinity (Kd = 4.6 nM). Anti-cis-UCA antibody precipitates radiolabeled 5-HT, and the binding is inhibited by excess 5-HT and/or excess cis-UCA. Similarly, anti-5-HT antibody precipitates radiolabeled cis-UCA, and the binding is inhibited by excess 5-HT or excess cis-UCA. Calcium mobilization was activated when a mouse fibroblast line, stably transfected with the human 5-HT2A receptor, was treated with cis-UCA. Cis-UCA-induced calcium mobilization was blocked with a selective 5-HT2A receptor antagonist. UV- and cis-UCA-induced immune suppression was blocked by antiserotonin antibodies or by treating the mice with 5-HT2A receptor antagonists. Our findings identify cis-UCA as a serotonin receptor ligand and indicate that the immunosuppressive effects of cis-UCA and UV radiation are mediated by activation of the 5-HT2A receptor. PMID:17085585

Radiosynthesis and evaluation of 11C-CIMBI-5 as a 5-HT2A receptor agonist radioligand for PET

DEFF Research Database (Denmark)

Ettrup, Anders; Palner, Mikael; Gillings, Nic

2010-01-01

PET brain imaging of the serotonin 2A (5-hydroxytryptamine 2A, or 5-HT(2A)) receptor has been widely used in clinical studies, and currently, several well-validated radiolabeled antagonist tracers are used for in vivo imaging of the cerebral 5-HT(2A) receptor. Access to 5-HT(2A) receptor agonist...... PET tracers would, however, enable imaging of the active, high-affinity state of receptors, which may provide a more meaningful assessment of membrane-bound receptors. In this study, we radiolabel the high-affinity 5-HT(2A) receptor agonist 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-[(11)C-OCH(3......)]methoxybenzyl)ethanamine ((11)C-CIMBI-5) and investigate its potential as a PET tracer....

5-HT2A receptor deficiency alters the metabolic and transcriptional, but not the behavioral, consequences of chronic unpredictable stress

Directory of Open Access Journals (Sweden)

Minal Jaggar

2017-12-01

Full Text Available Chronic stress enhances risk for psychiatric disorders, and in animal models is known to evoke depression-like behavior accompanied by perturbed neurohormonal, metabolic, neuroarchitectural and transcriptional changes. Serotonergic neurotransmission, including serotonin2A (5-HT2A receptors, have been implicated in mediating specific aspects of stress-induced responses. Here we investigated the influence of chronic unpredictable stress (CUS on depression-like behavior, serum metabolic measures, and gene expression in stress-associated neurocircuitry of the prefrontal cortex (PFC and hippocampus in 5-HT2A receptor knockout (5-HT2A−/− and wild-type mice of both sexes. While 5-HT2A−/− male and female mice exhibited a baseline reduced anxiety-like state, this did not alter the onset or severity of behavioral despair during and at the cessation of CUS, indicating that these mice can develop stress-evoked depressive behavior. Analysis of metabolic parameters in serum revealed a CUS-evoked dyslipidemia, which was abrogated in 5-HT2A−/− female mice with a hyperlipidemic baseline phenotype. 5-HT2A−/− male mice in contrast did not exhibit such a baseline shift in their serum lipid profile. Specific stress-responsive genes (Crh, Crhr1, Nr3c1, and Nr3c2, trophic factors (Bdnf, Igf1 and immediate early genes (IEGs (Arc, Fos, Fosb, Egr1-4 in the PFC and hippocampus were altered in 5-HT2A−/− mice both under baseline and CUS conditions. Our results support a role for the 5-HT2A receptor in specific metabolic and transcriptional, but not behavioral, consequences of CUS, and highlight that the contribution of the 5-HT2A receptor to stress-evoked changes is sexually dimorphic. Keywords: 5-HT2A−/− mice, Prefrontal cortex, Hippocampus, Gene expression, Sexual dimorphism, Despair

Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP kinase

Directory of Open Access Journals (Sweden)

Guan Kunliang

2003-06-01

Full Text Available Abstract Background G protein-coupled receptors (GPCRs interact with heterotrimeric GTP-binding proteins (G proteins to modulate acute changes in intracellular messenger levels and ion channel activity. In contrast, long-term changes in cellular growth, proliferation and differentiation are often mediated by tyrosine kinase receptors and certain GPCRs by activation of mitogen-activated protein (MAP kinases. Complex interactions occur between these signaling pathways, but the specific mechanisms of such regulatory events are not well-understood. In particular it is not clear whether GPCRs are modulated by tyrosine kinase receptor-MAP kinase pathways. Results Here we describe tyrosine kinase receptor regulation of a GPCR via MAP kinase. Insulin reduced the activity of the 5-HT2C receptor in choroid plexus cells which was blocked by the MAP kinase kinase (MEK inhibitor, PD 098059. We demonstrate that the inhibitory effect of insulin and insulin-like growth factor type 1 (IGF-1 on the 5-HT2C receptor is dependent on tyrosine kinase, RAS and MAP kinase. The effect may be receptor-specific: insulin had no effect on another GPCR that shares the same G protein signaling pathway as the 5-HT2C receptor. This effect is also direct: activated MAP kinase mimicked the effect of insulin, and removing a putative MAP kinase site from the 5-HT2C receptor abolished the effect of insulin. Conclusion These results show that insulin signaling can inhibit 5-HT2C receptor activity and suggest that MAP kinase may play a direct role in regulating the function of a specific GPCR.

Trait aggression and trait impulsivity are not related to frontal cortex 5-HT2A receptor binding in healthy individuals

DEFF Research Database (Denmark)

da Cunha-Bang, Sophie; Stenbæk, Dea Siggaard; Holst, Klaus

2013-01-01

age 47.0±18.7, range 23-86) to determine if trait aggression and trait impulsivity were related to frontal cortex 5-HT2A receptor binding (5-HT2AR) as measured with [(18)F]-altanserin PET imaging. Trait aggression and trait impulsivity were assessed with the Buss-Perry Aggression Questionnaire (AQ...... and the AQ or BIS-11 total scores. Also, there was no significant interaction between gender and frontal cortex 5-HT2AR in predicting trait aggression and trait impulsivity. This is the first study to examine how 5-HT2AR relates to trait aggression and trait impulsivity in a large sample of healthy......Numerous studies indicate that the serotonergic (5-HT) transmitter system is involved in the regulation of impulsive aggression and there is from post-mortem, in vivo imaging and genetic studies evidence that the 5-HT2A receptor may be involved. We investigated 94 healthy individuals (60 men, mean...

Activation of 5-HT2 receptors enhances the release of acetylcholine in the prefrontal cortex and hippocampus of the rat.

Science.gov (United States)

Nair, Sunila G; Gudelsky, Gary A

2004-09-15

The role of 5-HT2 receptors in the regulation of acetylcholine (ACh) release was examined in the medial prefrontal cortex and dorsal hippocampus using in vivo microdialysis. The 5-HT(2A/2C) agonist +/-1-(2,5-dimethoxy-4-iodophenyl) -2- aminopropane hydrochloride (DOI) (1 and 2 mg/kg, i.p.) significantly increased the extracellular concentration of ACh in both brain regions, and this response was attenuated in rats treated with the 5-HT(2A/2B/2C) antagonist LY-53,857 (3 mg/kg, i.p.). Treatment with LY-53,857 alone did not significantly alter ACh release in either brain region The 5-HT(2C) agonist 6-chloro-2-(1-piperazinyl)-pyrazine) (MK-212) (5 mg/kg, i.p.) significantly enhanced the release of ACh in both the prefrontal cortex and hippocampus, whereas the 5-HT2 agonist mescaline (10 mg/kg, i.p.) produced a 2-fold increase in ACh release only in the prefrontal cortex. Intracortical, but not intrahippocampal, infusion of DOI (100 microM) significantly enhanced the release of ACh, and intracortical infusion of LY-53,857 (100 microM) significantly attenuated this response. These results suggest that the release of ACh in the prefrontal cortex and hippocampus is influenced by 5-HT2 receptor mechanisms. The increase in release of ACh induced by DOI in the prefrontal cortex, but not in the hippocampus, appears to be due to 5-HT2 receptor mechanisms localized within this brain region. Furthermore, it appears that the prefrontal cortex is more sensitive than the dorsal hippocampus to the stimulatory effect of 5-HT2 agonists on ACh release.

Magnetic ''islandography'' in tokamaks

International Nuclear Information System (INIS)

Callen, J.D.; Waddell, B.V.; Hicks, H.R.

1978-09-01

Tearing modes are shown to be responsible for most of the experimentally observed macroscopic behavior of tokamak discharges. The effects of these collective magnetic perturbations on magnetic topology and plasma transport in tokamaks are shown to provide plausible explanations for: internal disruptions (m/n = 1); Mirnov oscillations (m/n = 2,3...); and major disruptions (coupling of 2/1-3/2 modes). The nonlinear evolution of the tearing modes is followed with fully three-dimensional computer codes. The effects on plasma confinement of the magnetic islands or stochastic field lines induced by the macroscopic tearing modes are discussed and compared with experiment. Finally, microscopic magnetic perturbations are shown to provide a natural model for the microscopic anomalous transport processes in tokamaks

Novel 5-HT6 receptor antagonists/D2 receptor partial agonists targeting behavioral and psychological symptoms of dementia.

Science.gov (United States)

Kołaczkowski, Marcin; Marcinkowska, Monika; Bucki, Adam; Śniecikowska, Joanna; Pawłowski, Maciej; Kazek, Grzegorz; Siwek, Agata; Jastrzębska-Więsek, Magdalena; Partyka, Anna; Wasik, Anna; Wesołowska, Anna; Mierzejewski, Paweł; Bienkowski, Przemyslaw

2015-03-06

We describe a novel class of designed multiple ligands (DMLs) combining serotonin 5-HT6 receptor (5-HT6R) antagonism with dopamine D2 receptor (D2R) partial agonism. Prototype hybrid molecules were designed using docking to receptor homology models. Diverse pharmacophore moieties yielded 3 series of hybrids with varying in vitro properties at 5-HT6R and D2R, and at M1 receptor and hERG channel antitargets. 4-(piperazin-1-yl)-1H-indole derivatives showed highest antagonist potency at 5-HT6R, with 7-butoxy-3,4-dihydroquinolin-2(1H)-one and 2-propoxybenzamide derivatives having promising D2R partial agonism. 2-(3-(4-(1-(phenylsulfonyl)-1H-indol-4-yl)piperazin-1-yl)propoxy)benzamide (47) exhibited nanomolar affinity at both 5-HT6R and D2R and was evaluated in rat models. It displayed potent antidepressant-like and anxiolytic-like activity in the Porsolt and Vogel tests, respectively, more pronounced than that of a reference selective 5-HT6R antagonist or D2R partial agonist. In addition, 47 also showed antidepressant-like activity (Porsolt's test) and anxiolytic-like activity (open field test) in aged (>18-month old) rats. In operant conditioning tests, 47 enhanced responding for sweet reward in the saccharin self-administration test, consistent with anti-anhedonic properties. Further, 47 facilitated extinction of non-reinforced responding for sweet reward, suggesting potential procognitive activity. Taken together, these studies suggest that DMLs combining 5-HT6R antagonism and D2R partial agonism may successfully target affective disorders in patients from different age groups without a risk of cognitive deficits. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Rapid desensitization and resensitization of 5-HT2 receptor mediated phosphatidyl inositol hydrolysis by serotonin agonists in quiescent calf aortic smooth muscle cells

International Nuclear Information System (INIS)

Pauwels, P.J.; Van Gompel, P.; Leysen, J.E.

1990-01-01

Agonist regulation of 5-hydroxytryptamine 2 (5-HT 2 ) receptors was studied in calf aortic smooth muscle cultures incubated in a quiescent, defined synthetic medium that does not stimulate cell proliferation, but that provides cells with supplements that maintain cell viability. In these cells, 5-hydroxytryptamine (5-HT)-induced [ 3 H]inositol phosphates accumulation showed the characteristics of a 5-HT 2 receptor coupled transducing system according to the inhibition of the response by 5-HT 2 antagonists at nanomolar concentrations. The 5-HT 2 receptor coupled response became rapidly desensitized during continued incubation with 5-HT and 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM); nearly full desensitization was obtained in two hours with 10 μM 5-HT and DOM pretreatment. The recovery of the response had a half-live of 5 hours after 2 hours pretreatment and of 9.5 to 12.5 hours after 24 to 96 hours agonist pretreatment. The DOM-induced desensitization of the 5-HT 2 receptor coupled response was fully blocked by 0.1 μM cinanserin. Cinanserin alone did not induce desensitization or up-regulation of the 5-HT 2 receptor coupled response at 0.1 μM

T-2 toxin/HT-2 toxin and ochratoxin A ELISAs development and in-house validation in food in accordance with the commission regulation (EU) no 519/2014

NARCIS (Netherlands)

Oplatowska-Stachowiak, Michalina; Kleintjens, Tim; Sajic, Nermin; Haasnoot, Willem; Campbell, Katrina; Elliott, Christopher T.; Salden, Martin

2017-01-01

T-2 toxin/HT-2 toxin (T-2/HT-2) and ochratoxin A (OTA) are mycotoxins that can contaminate a variety of agricultural commodities. To protect consumers’ health, indicative limits for T-2/HT-2 and maximum limits for OTA have been set by the European Commission, requiring food business operators and

TOKOPS: Tokamak Reactor Operations Study: The influence of reactor operations on the design and performance of tokamaks with solid-breeder blankets: Final report

International Nuclear Information System (INIS)

Conn, R.W.; Ghoniem, N.M.; Firestone, M.A.

1986-09-01

Reactor system operation and procedures have a profound impact on the conception and design of power plants. These issues are studied here using a model tokamak system employing a solid-breeder blanket. The model blanket is one which has evolved from the STARFIRE and BCSS studies. The reactor parameters are similar to those characterizing near-term fusion engineering reactors such as INTOR or NET (Next European Tokamak). Plasma startup, burn analysis, and methods for operation at various levels of output power are studied. A critical, and complicating, element is found to be the self-consistent electromagnetic response of the system, including the presence of the blanket and the resulting forces and loadings. Fractional power operation, and the strategy for burn control, is found to vary depending on the scaling law for energy confinement, and an extensive study is reported. Full-power reactor operation is at a neutron wall loading pf 5 MW/m 2 and a surface heat flux of 1 MW/m 2 . The blanket is a pressurized steel module with bare beryllium rods and low-activation HT-9-(9-C-) clad LiAlO 2 rods. The helium coolant pressure is 5 MPa, entering the module at 297 0 C and exiting at 550 0 C. The system power output is rated at 1000 MW(e). In this report, we present our findings on various operational scenarios and their impact on system design. We first start with the salient aspects of operational physics. Time-dependent analyses of the blanket and balance of plant are then presented. Separate abstracts are included for each chapter

Synthesis and in vivo evaluation of [O-methyl-{sup 11}C](2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine as a 5-HT{sub 2A} receptor PET ligand

Energy Technology Data Exchange (ETDEWEB)

Kumar, J.S. Dileep [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States)]. E-mail: dk2038@columbia.edu; Prabhakaran, Jaya [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Erlandsson, Kjell [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Majo, Vattoly J. [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Simpson, Norman R. [Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Pratap, Mali [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Heertum, Ronald L. van [Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Mann, J. John [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Parsey, Ramin V. [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States)

2006-05-15

The serotonin{sub 2A} (5-HT{sub 2A}) receptor is implicated in the pathophysiology of schizophrenia and mood disorders, and in vivo studies of this receptor would be of value in studying the pathophysiology of these disorders and in measuring the relationship of clinical response to receptor occupancy for 5-HT{sub 2A} antagonists such as atypical antipsychotics. Therefore, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)-phenyl]ethyl] phenoxy]ethyl-1-methylpyrrolidine (MPM) (13), a selective and high-affinity (K {sub i}=0.79 nM) 5HT{sub 2A} antagonist, has been radiolabeled with carbon-11 by O-methylation of the corresponding desmethyl analogue (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-hydroxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine (12) with [{sup 11}C]methyltriflate in order to determine the suitability of [{sup 11}C]MPM to quantify 5-HT{sub 2A} in living brain using PET. Desmethyl-MPM 12 and standard MPM were prepared, starting from 3-hydroxymethylphenol (2), in excellent yield. The yield obtained for radiolabeling was 40{+-}5% (EOB), and the total synthesis time was 30 min at EOS. PET studies with [{sup 11}C]MPM in baboon showed a distribution in the brain consistent with the known distribution of 5-HT{sub 2A} receptors. The time-activity curves for the high-binding regions peaked at {approx}45 min after injection. Blocking studies with M100907 demonstrated not only 38-57% blocking of tracer binding in brain regions known to have 5-HT{sub 2A} receptors but also 38% blocking in cerebellum, which has a low 5-HT{sub 2A} receptor concentration. Although [{sup 11}C]MPM exhibits appropriate kinetics in baboon for imaging 5-HT{sub 2A} receptors, its specific binding in cerebellum and higher proportion of nonspecific binding limit its usefulness for the in vivo quantification of 5-HT{sub 2A} receptors with PET.

The inhibition of cholera toxin-induced 5-HT release by the 5-HT3 receptor antagonist, granisetron, in the rat

Science.gov (United States)

Turvill, J L; Connor, P; Farthing, M J G

2000-01-01

The secretagogue 5-hydroxytryptamine (5-HT) is implicated in the pathophysiology of cholera. 5-HT released from enterochromaffin cells after cholera toxin exposure is thought to activate non-neuronally (5-HT2 dependent) and neuronally (5-HT3 dependent) mediated water and electrolyte secretion. CT-secretion can be reduced by preventing the release of 5-HT. Enterochromaffin cells possess numerous receptors that, under basal conditions, modulate 5-HT release. These include basolateral 5-HT3 receptors, the activation of which is known to enhance 5-HT release. Until now, 5-HT3 receptor antagonists (e.g. granisetron) have been thought to inhibit cholera toxin-induced fluid secretion by blockading 5-HT3 receptors on secretory enteric neurones. Instead we postulated that they act by inhibiting cholera toxin-induced enterochromaffin cell degranulation. Isolated intestinal segments in anaesthetized male Wistar rats, pre-treated with granisetron 75 μg kg−1, lidoocaine 6 mg kg−1 or saline, were instilled with a supramaximal dose of cholera toxin or saline. Net fluid movement was determined by small intestinal perfusion or gravimetry and small intestinal and luminal fluid 5-HT levels were determined by HPLC with fluorimetric detection. Intraluminal 5-HT release was proportional to the reduction in tissue 5-HT levels and to the onset of water and electrolyte secretion, suggesting that luminal 5-HT levels reflect enterochromaffin cell activity. Both lidocaine and granisetron inhibited fluid secretion. However, granisetron alone, and proportionately, reduced 5-HT release. The simultaneous inhibition of 5-HT release and fluid secretion by granisetron suggests that 5-HT release from enterochromaffin cells is potentiated by endogenous 5-HT3 receptors. The accentuated 5-HT release promotes cholera toxin-induced fluid secretion. PMID:10882387

Decreased frontal serotonin 5-HT2a receptor binding index in deliberate self-harm patients

International Nuclear Information System (INIS)

Audenaert, K.; Laere, K. van; Dierckx, R.A.; Dumont, F.; Slegers, G.; Mertens, J.; Heeringen, C. van

2001-01-01

Studies of serotonin metabolites in body fluids in attempted suicide patients and of post-mortem brain tissue of suicide victims have demonstrated the involvement of the serotonergic neurotransmission system in the pathogenesis of suicidal behaviour. Recently developed neuroimaging techniques offer the unique possibility of investigating in vivo the functional characteristics of this system. In this study the 5-HT 2a receptor population of patients who had recently attempted suicide was studied by means of the highly specific radio-iodinated 5-HT 2a receptor antagonist 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl] -5-iodo-2-methox ybenzamide or 123 I-5-I-R91150. Nine patients who had recently (1-7 days) attempted suicide and 12 age-matched healthy controls received an intravenous injection of 185 MBq 123 I-5-I-R91150 and were scanned with high-resolution brain single-photon emission tomography (SPET). Stereotactic realigned images were analysed semi-quantitatively using predefined volumes of interest. Serotonin binding capacity was expressed as the ratio of specific to non-specific activity. The cerebellum was used as a measure of non-specific activity. An age-dependent 5-HT 2a binding index was found, in agreement with previous literature. Deliberate self-harm patients had a significantly reduced mean frontal binding index after correction for age (P=0.002) when compared with controls. The reduction was more pronounced among deliberate self-injury patients (DSI) (P 2a serotonin receptor system in attempted suicide patients who are free of drugs influencing the serotonergic system shows in vivo evidence of a decreased frontal binding index of the 5-HT 2a receptor, indicating a decrease in the number and/or in the binding affinity of 5-HT 2a receptors. (orig.)

Survey of T-2/HT-2 toxins in unprocessed cereals, food and feed coming from Croatia and Bosnia & Herzegovina.

Science.gov (United States)

Pleadin, Jelka; Vasilj, Višnja; Kudumija, Nina; Petrović, Danijela; Vilušić, Milica; Škrivanko, Mario

2017-06-01

The aim of this study was to investigate into the level of T-2/HT-2 toxins in different unprocessed cereals (n=201), as well as in marketed cereal-based products (n=58), feed components (n=191) and feedstuffs (n=91) coming from Croatia and Bosnia & Herzegovina. The number of positive samples of unprocessed cereals for food production (>LOD) ranged from 30.4% in barley to 68.8% in oat whereas for feed components ranged from 26.9% in wheat to 86.1% in oat. The maximal values found in unprocessed oat and oat-based feed components were 304.2μg/kg and 521.0μg/kg, respectively. As for final products, the highest T-2/HT-2 concentrations were determined in oat flakes (89.4μg/kg) and calf feed (129.3μg/kg). Despite of the increased T-2/HT-2 concentrations found in some of the samples, the obtained values were unanimously lower than the indicative levels given as recommendations above which further investigations should be necessary performed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Detailed characterization of the in vitro pharmacological and pharmacokinetic properties of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine (25CN-NBOH), a highly selective and brain-penetrant 5-HT2A receptor agonist

DEFF Research Database (Denmark)

Jensen, Anders A; McCorvy, John D; Petersen, Sebastian Leth

2017-01-01

]ketanserin/[3H]mesulergine, [3H]LSD and [3H]Cimbi-36 binding assays (Ki 2C/Ki 2A ratio range 52-81, Ki 2B/Ki 2A ratio 37). Moreover, in inositol phosphate and intracellular Ca2+ mobilization assays 25CN-NBOH exhibited 30- to 180-fold 5-HT2A/5-HT2C selectivities and 54-fold 5-HT2A/5-HT2B selectivity as measured...

MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor

Directory of Open Access Journals (Sweden)

Drew J. Puxty

2017-07-01

Full Text Available Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol, which are elevated by MDMA. In order to investigate the role of the 5-HT2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg, combined with placebo or a single oral dose of the 5-HT2 receptor blocker ketanserin (40 mg. Twenty healthy recreational MDMA users filled out a dissociative states scale (CADSS 90 min after treatments, which was preceded and followed by assessment of a number of biological parameters (cortisol levels, heart rate, MDMA blood concentrations. Findings showed that MDMA induced a dissociative state but this effect was not counteracted by pre-treatment with ketanserin. Heart rate was the only biological parameter that correlated with the MDMA-induced dissociative state, but an absence of correlation between these measures when participants were pretreated with ketanserin suggests an absence of directional effects of heart rate on dissociative state. It is suggested that the 5-HT2 receptor does not mediate the dissociative effects caused by a single dose of MDMA. Further research is needed to determine the exact neurobiology underlying this effect and whether these effects contribute to the therapeutic potential of MDMA.

Development of high-speed and wide-angle visible observation diagnostics on Experimental Advanced Superconducting Tokamak using catadioptric optics

International Nuclear Information System (INIS)

Yang, J. H.; Hu, L. Q.; Zang, Q.; Han, X. F.; Shao, C. Q.; Sun, T. F.; Chen, H.; Wang, T. F.; Li, F. J.; Hu, A. L.; Yang, X. F.

2013-01-01

A new wide-angle endoscope for visible light observation on the Experimental Advanced Superconducting Tokamak (EAST) has been recently developed. The head section of the optical system is based on a mirror reflection design that is similar to the International Thermonuclear Experimental Reactor-like wide-angle observation diagnostic on the Joint European Torus. However, the optical system design has been simplified and improved. As a result, the global transmittance of the system is as high as 79.6% in the wavelength range from 380 to 780 nm, and the spatial resolution is <5 mm for the full depth of field (4000 mm). The optical system also has a large relative aperture (1:2.4) and can be applied in high-speed camera diagnostics. As an important diagnostic tool, the optical system has been installed on the HT-7 (Hefei Tokamak-7) for its final experimental campaign, and the experiments confirmed that it can be applied to the investigation of transient processes in plasma, such as ELMy eruptions in H-mode, on EAST

D-serine deficiency attenuates the behavioral and cellular effects induced by the hallucinogenic 5-HT(2A) receptor agonist DOI

DEFF Research Database (Denmark)

Santini, Martin A; Balu, Darrick T; Puhl, Matthew D

2014-01-01

Both the serotonin and glutamate systems have been implicated in the pathophysiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. Psychedelic drugs act through the serotonin 2A receptor (5-HT2AR), and elicit a head-twitch response (HTR) in mice, which directly...... correlates to 5-HT2AR activation and is absent in 5-HT2AR knockout mice. The precise mechanism of this response remains unclear, but both an intrinsic cortico-cortical pathway and a thalamo-cortical pathway involving glutamate release have been proposed. Here, we used a genetic model of NMDAR hypofunction......RNA. These altered functional responses in SRKO mice were not associated with changes in cortical or hippocampal 5-HT levels or in 5-HT2AR and metabotropic glutamate-2 receptor (mGluR2) mRNA and protein expression. Together, these findings suggest that D-serine-dependent NMDAR activity is involved in mediating...

Decreased frontal serotonin 5-HT{sub 2a} receptor binding index in deliberate self-harm patients

Energy Technology Data Exchange (ETDEWEB)

Audenaert, K. [Dept. of Psychiatry and Medical Psychology, Ghent University Hospital (Belgium); Dept. of Nuclear Medicine, Ghent University Hospital (Belgium); Laere, K. van; Dierckx, R.A. [Dept. of Nuclear Medicine, Ghent University Hospital (Belgium); Dumont, F.; Slegers, G. [Dept. of Radiopharmacy, Ghent Univ. (Belgium); Mertens, J. [VUB-Cyclotron, Brussels (Belgium); Heeringen, C. van [Dept. of Psychiatry and Medical Psychology, Ghent University Hospital (Belgium)

2001-02-01

Studies of serotonin metabolites in body fluids in attempted suicide patients and of post-mortem brain tissue of suicide victims have demonstrated the involvement of the serotonergic neurotransmission system in the pathogenesis of suicidal behaviour. Recently developed neuroimaging techniques offer the unique possibility of investigating in vivo the functional characteristics of this system. In this study the 5-HT{sub 2a} receptor population of patients who had recently attempted suicide was studied by means of the highly specific radio-iodinated 5-HT{sub 2a} receptor antagonist 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide or {sup 123}I-5-I-R91150. Nine patients who had recently (1-7 days) attempted suicide and 12 age-matched healthy controls received an intravenous injection of 185 MBq {sup 123}I-5-I-R91150 and were scanned with high-resolution brain single-photon emission tomography (SPET). Stereotactic realigned images were analysed semi-quantitatively using predefined volumes of interest. Serotonin binding capacity was expressed as the ratio of specific to non-specific activity. The cerebellum was used as a measure of non-specific activity. An age-dependent 5-HT{sub 2a} binding index was found, in agreement with previous literature. Deliberate self-harm patients had a significantly reduced mean frontal binding index after correction for age (P=0.002) when compared with controls. The reduction was more pronounced among deliberate self-injury patients (DSI) (P<0.001) than among deliberate self-poisoning patients (DSP). Frontal binding index was significantly lower in DSI patients than in DSP suicide attempters (P<0.001). It is concluded that brain SPET of the 5-HT{sub 2a} serotonin receptor system in attempted suicide patients who are free of drugs influencing the serotonergic system shows in vivo evidence of a decreased frontal binding index of the 5-HT{sub 2a} receptor, indicating a decrease in the number and/or in

Tolerance to LSD and DOB induced shaking behaviour: differential adaptations of frontocortical 5-HT(2A) and glutamate receptor binding sites.

Science.gov (United States)

Buchborn, Tobias; Schröder, Helmut; Dieterich, Daniela C; Grecksch, Gisela; Höllt, Volker

2015-03-15

Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD) and dimethoxy-bromoamphetamine (DOB), provoke stereotype-like shaking behaviour in rodents, which is hypothesised to engage frontocortical glutamate receptor activation secondary to serotonin2A (5-HT2A) related glutamate release. Challenging this hypothesis, we here investigate whether tolerance to LSD and DOB correlates with frontocortical adaptations of 5-HT2A and/or overall-glutamate binding sites. LSD and DOB (0.025 and 0.25 mg/kg, i.p.) induce a ketanserin-sensitive (0.5 mg/kg, i.p., 30-min pretreatment) increase in shaking behaviour (including head twitches and wet dog shakes), which with repeated application (7× in 4 ds) is undermined by tolerance. Tolerance to DOB, as indexed by DOB-sensitive [(3)H]spiroperidol and DOB induced [(35)S]GTP-gamma-S binding, is accompanied by a frontocortical decrease in 5-HT2A binding sites and 5-HT2 signalling, respectively; glutamate-sensitive [(3)H]glutamate binding sites, in contrast, remain unchanged. As to LSD, 5-HT2 signalling and 5-HT2A binding, respectively, are not or only marginally affected, yet [(3)H]glutamate binding is significantly decreased. Correlation analysis interrelates tolerance to DOB to the reduced 5-HT2A (r=.80) as well as the unchanged [(3)H]glutamate binding sites (r=.84); tolerance to LSD, as opposed, shares variance with the reduction in [(3)H]glutamate binding sites only (r=.86). Given that DOB and LSD both induce tolerance, one correlating with 5-HT2A, the other with glutamate receptor adaptations, it might be inferred that tolerance can arise at either level. That is, if a hallucinogen (like LSD in our study) fails to induce 5-HT2A (down-)regulation, glutamate receptors (activated postsynaptic to 5-HT2A related glutamate release) might instead adapt and thus prevent further overstimulation of the cortex. Copyright © 2014 Elsevier B.V. All rights reserved.

The effects of benzofury (5-APB) on the dopamine transporter and 5-HT2-dependent vasoconstriction in the rat.

Science.gov (United States)

Dawson, Patrick; Opacka-Juffry, Jolanta; Moffatt, James D; Daniju, Yusuf; Dutta, Neelakshi; Ramsey, John; Davidson, Colin

2014-01-03

5-APB, commonly marketed as 'benzofury' is a new psychoactive substance and erstwhile 'legal high' which has been implicated in 10 recent drug-related deaths in the UK. This drug was available on the internet and in 'head shops' and was one of the most commonly sold legal highs up until its recent UK temporary ban (UK Home Office). Despite its prominence, very little is known about its pharmacology. This study was undertaken to examine the pharmacology of 5-APB in vitro. We hypothesised that 5-APB would activate the dopamine and 5-HT systems which may underlie its putative stimulant and hallucinogenic effects. Autoradiographic studies showed that 5-APB displaced both [(125)I] RTI-121 and [(3)H] ketanserin from rat brain tissue suggesting affinity at the dopamine transporter and 5-HT2 receptor sites respectively. Voltammetric studies in rat accumbens brain slices revealed that 5-APB slowed dopamine reuptake, and at high concentrations caused reverse transport of dopamine. 5-APB also caused vasoconstriction of rat aorta, an effect antagonised by the 5-HT2A receptor antagonist ketanserin, and caused contraction of rat stomach fundus, which was reversed by the 5-HT2B receptor antagonist RS-127445. These data show that 5-APB interacts with the dopamine transporter and is an agonist at the 5-HT2A and 5-HT2B receptors in the rat. Thus 5-APB's pharmacology is consistent with it having both stimulant and hallucinogenic properties. In addition, 5-APB's activity at the 5-HT2B receptor may cause cardiotoxicity. © 2013.

Tokamak Systems Code

International Nuclear Information System (INIS)

Reid, R.L.; Barrett, R.J.; Brown, T.G.

1985-03-01

The FEDC Tokamak Systems Code calculates tokamak performance, cost, and configuration as a function of plasma engineering parameters. This version of the code models experimental tokamaks. It does not currently consider tokamak configurations that generate electrical power or incorporate breeding blankets. The code has a modular (or subroutine) structure to allow independent modeling for each major tokamak component or system. A primary benefit of modularization is that a component module may be updated without disturbing the remainder of the systems code as long as the imput to or output from the module remains unchanged

Paroxetine and Low-dose Risperidone Induce Serotonin 5-HT1A and Dopamine D2 Receptor Heteromerization in the Mouse Prefrontal Cortex.

Science.gov (United States)

Kolasa, Magdalena; Solich, Joanna; Faron-Górecka, Agata; Żurawek, Dariusz; Pabian, Paulina; Łukasiewicz, Sylwia; Kuśmider, Maciej; Szafran-Pilch, Kinga; Szlachta, Marta; Dziedzicka-Wasylewska, Marta

2018-05-01

Recently, it has been shown that serotonin 5-HT 1A receptor interacts with dopamine D2 receptor in vitro. However, the existence of 5-HT 1A -D2 heteromers in native tissue remains unexplored. In the present study, we investigated 5-HT 1A -D2 receptor heteromerization in mice treated acutely or chronically with paroxetine (10 mg/kg) or risperidone (0.05 mg/kg). Receptor heteromerization was visualized and quantified in the mouse brain by in situ proximity ligation assay (PLA). Additionally, we aimed to determine the cellular localization of 5-HT 1A -D2 receptor heteromers in mouse adult primary neuronal cells by immunofluorescent staining with markers for astrocytes (GFAP) and neurons (NeuN and MAP2). The results from the current study demonstrated that 5-HT 1A and D2 receptor co-localization and heteromerization occurred in the mouse prefrontal cortex. Counterstaining after PLA confirmed neuronal (pyramidal and GABAergic) as well as astrocytal localization of 5-HT 1A -D2 receptor heteromers. Chronic administration of paroxetine or risperidone increased the level of 5-HT 1A -D2 receptor heteromers in the prefrontal cortex. These changes were not accompanied by any changes in the expression of mRNAs (measured by in situ hybridization) or densities of 5-HT 1A and D2 receptors (quantified by receptor autoradiography with [3H]8-OH-DPAT and [3H]domperidone, respectively), what all indicated that paroxetine and risperidone facilitated 5-HT 1A -D2 heteromer formation independently of the receptor expression. In vitro homogenous time-resolved FRET (HTRF) study confirmed the ability of tested drugs to influence the human 5-HT 1A -D2 heteromer formation. The obtained data indicate that the increase in 5-HT 1A -D2 receptor heteromerization is a common molecular characteristic of paroxetine and low-dose risperidone treatment. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Correlating the Metabolic Stability of Psychedelic 5-HT2A Agonists with Anecdotal Reports of Human Oral Bioavailability

DEFF Research Database (Denmark)

Leth-Petersen, Sebastian; Bundgaard, Christoffer; Hansen, Martin

2014-01-01

2,5-Dimethoxyphenethylamines and their N-benzylated derivatives are potent 5-HT2A agonists with psychedelic effects in humans. The N-benzylated derivatives are among the most selective 5-HT2A agonists currently available and their usage as biochemical and brain imaging tools is increasing, yet ve...

The ARIES tokamak reactor study

International Nuclear Information System (INIS)

1989-10-01

The ARIES study is a community effort to develop several visions of tokamaks as fusion power reactors. The aims are to determine the potential economics, safety, and environmental features of a range of possible tokamak reactors, and to identify physics and technology areas with the highest leverage for achieving the best tokamak reactor. Three ARIES visions are planned, each having a different degree of extrapolation from the present data base in physics and technology. The ARIES-I design assumes a minimum extrapolation from current tokamak physics (e.g., 1st stability) and incorporates technological advances that can be available in the next 20 to 30 years. ARIES-II is a DT-burning tokamak which would operate at a higher beta in the 2nd MHD stability regime. It employs both potential advances in the physics and expected advances in technology and engineering. ARIES-II will examine the potential of the tokamak and the D 3 He fuel cycle. This report is a collection of 14 papers on the results of the ARIES study which were presented at the IEEE 13th Symposium on Fusion Engineering (October 2-6, 1989, Knoxville, TN). This collection describes the ARIES research effort, with emphasis on the ARIES-I design, summarizing the major results, the key technical issues, and the central conclusions

Novel spirotetracyclic zwitterionic dual H(1)/5-HT(2A) receptor antagonists for the treatment of sleep disorders.

Science.gov (United States)

Gianotti, Massimo; Botta, Maurizio; Brough, Stephen; Carletti, Renzo; Castiglioni, Emiliano; Corti, Corrado; Dal-Cin, Michele; Delle Fratte, Sonia; Korajac, Denana; Lovric, Marija; Merlo, Giancarlo; Mesic, Milan; Pavone, Francesca; Piccoli, Laura; Rast, Slavko; Roscic, Maja; Sava, Anna; Smehil, Mario; Stasi, Luigi; Togninelli, Andrea; Wigglesworth, Mark J

2010-11-11

Histamine H(1) and serotonin 5-HT(2A) receptors mediate two different mechanisms involved in sleep regulation: H(1) antagonists are sleep inducers, while 5-HT(2A) antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H(1)/5-HT(2A) potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H(1)/5-HT(2A) activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.

5HT{sub 2} receptors in cerebral cortex of migraineurs studied using PET and {sup 18}F-fluorosetoperoene

Energy Technology Data Exchange (ETDEWEB)

Chabriat, H.; Tehindrazanarivelo, A.; Vera, P.; Samson, Y.; Pappata, S.; Boullais, N.; Bousser, M.G. [Hospital Saint Antoine, Paris (France)

1995-04-01

Since the brain 5HT{sub 2} might be implicated in migraine pathogenesis, the authors have used positron emission tomography and {sup 18}F-fluorosetoperone, a 5HT{sub 2} specific radioligand, to investigate in vivo the cortical 5HT{sub 2} receptors in migraine subjects. Nine migraineurs who had either migraine with and without aura or only migraine without aura were studied between attacks. 12 unmedicated healthy subjects of similar mean age were used as controls. Brain radioactivity was measured after {sup 18}F-setoperone IV injection for 90 min. A decrease of the regional specific distribution volumes (SDV) of the ligand was observed both in migraineurs and in controls. The age adjusted group means of SDV did not differ between patients and controls for the whole and for the right or left frontal, temporal, parietal and occipital cortex. These results suggest that cortical 5HT{sub 2} receptors may be unaltered between attacks in migraine sufferers. 30 refs., 4 figs., 2 tabs.

Deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and early postnatal lethality.

Directory of Open Access Journals (Sweden)

Jacobus J Dudok

Full Text Available The serotonin (5-HT system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT promoter. The majority of mutant mice died within a few days after birth. Immunohistochemical analysis of brains of these mice showed that initially 5-HT neurons are formed and the cortex is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections were present in the cortex. The 5-HT system of mice heterozygous for the floxed Munc18-1 allele was indistinguishable from control mice. These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival.

The effects of the selective 5-HT(2C) receptor antagonist SB 242084 on learned helplessness in male Fischer 344 rats.

Science.gov (United States)

Strong, Paul V; Greenwood, Benjamin N; Fleshner, Monika

2009-05-01

Rats exposed to an uncontrollable stressor demonstrate a constellation of behaviors such as exaggerated freezing and deficits in shuttle box escape learning. These behaviors in rats have been called learned helplessness and have been argued to model human stress-related mood disorders. Learned helplessness is thought to be caused by hyperactivation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) and a subsequent exaggerated release of 5-HT in DRN projection sites. Blocking 5-HT(2C) receptors in the face of an increase in serotonin can alleviate anxiety behaviors in some animal models. However, specific 5-HT receptor subtypes involved in learned helplessness remain unknown. The current experiments tested the hypothesis that 5-HT(2C) receptor activation is necessary and sufficient for the expression of learned helplessness. The selective 5-HT(2C) receptor antagonist SB 242084 (1.0 mg/kg) administered i.p. to adult male Fischer 344 rats prior to shuttle box behavioral testing, but not before stress, blocked stress-induced deficits in escape learning but had no effect on the exaggerated shock-elicited freezing. The selective 5-HT(2C) receptor agonist CP-809101 was sufficient to produce learned helplessness-like behaviors in the absence of prior stress and these effects were blocked by pretreatment with SB 242084. Results implicate the 5-HT(2C) receptor subtype in mediating the shuttle box escape deficits produced by exposure to uncontrollable stress and suggest that different postsynaptic 5-HT receptor subtypes underlie the different learned helplessness behaviors.

Control system of neoclassical tearing modes in real time on HL-2A tokamak

Science.gov (United States)

Yan, Longwen; Ji, Xiaoquan; Song, Shaodong; Xia, Fan; Xu, Yuan; Ye, Jiruo; Jiang, Min; Chen, Wenjin; Sun, Tengfei; Liang, Shaoyong; Ling, Fei; Ma, Rui; Huang, Mei; Qu, Hongpeng; Song, Xianming; Yu, Deliang; Shi, Zhongbin; Liu, Yi; Yang, Qingwei; Xu, Min; Duan, Xuru; Liu, Yong

2017-11-01

The stability and performance of tokamak plasmas are routinely limited by various magneto-hydrodynamic instabilities, such as neoclassical tearing modes (NTMs). This paper presents a rather simple method to control the NTMs in real time (RT) on a tokamak, including the control principle of a feedback approach for RT suppression and stabilization for the NTMs. The control system combines Mirnov, electron cyclotron emission, and soft X-ray diagnostics used for determining the NTM positions. A methodology for fast detection of 2/1 or 3/2 NTM positions with 129 × 129 grid reconstruction is elucidated. The forty poloidal angles for steering the electron cyclotron resonance heating (ECRH)/electron cyclotron current drive launcher are used to establish the alignment of antenna mirrors with the center of the NTM and to ensure launcher emission intersecting with the rational surface of a magnetic island. Pilot experiments demonstrate the RT control capability to trace the conventional tearing modes (CTMs) in the HL-2A tokamak. The 2/1 CTMs have been suppressed or stabilized by the ECRH power deposition on site or with the steerable launcher.

Receptor⁻Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment.

Science.gov (United States)

Borroto-Escuela, Dasiel O; Narváez, Manuel; Ambrogini, Patrizia; Ferraro, Luca; Brito, Ismel; Romero-Fernandez, Wilber; Andrade-Talavera, Yuniesky; Flores-Burgess, Antonio; Millon, Carmelo; Gago, Belen; Narvaez, Jose Angel; Odagaki, Yuji; Palkovits, Miklos; Diaz-Cabiale, Zaida; Fuxe, Kjell

2018-06-03

Due to the binding to a number of proteins to the receptor protomers in receptor heteromers in the brain, the term "heteroreceptor complexes" was introduced. A number of serotonin 5-HT1A heteroreceptor complexes were recently found to be linked to the ascending 5-HT pathways known to have a significant role in depression. The 5-HT1A⁻FGFR1 heteroreceptor complexes were involved in synergistically enhancing neuroplasticity in the hippocampus and in the dorsal raphe 5-HT nerve cells. The 5-HT1A protomer significantly increased FGFR1 protomer signaling in wild-type rats. Disturbances in the 5-HT1A⁻FGFR1 heteroreceptor complexes in the raphe-hippocampal 5-HT system were found in a genetic rat model of depression (Flinders sensitive line (FSL) rats). Deficits in FSL rats were observed in the ability of combined FGFR1 and 5-HT1A agonist cotreatment to produce antidepressant-like effects. It may in part reflect a failure of FGFR1 treatment to uncouple the 5-HT1A postjunctional receptors and autoreceptors from the hippocampal and dorsal raphe GIRK channels, respectively. This may result in maintained inhibition of hippocampal pyramidal nerve cell and dorsal raphe 5-HT nerve cell firing. Also, 5-HT1A⁻5-HT2A isoreceptor complexes were recently demonstrated to exist in the hippocampus and limbic cortex. They may play a role in depression through an ability of 5-HT2A protomer signaling to inhibit the 5-HT1A protomer recognition and signaling. Finally, galanin (1⁻15) was reported to enhance the antidepressant effects of fluoxetine through the putative formation of GalR1⁻GalR2⁻5-HT1A heteroreceptor complexes. Taken together, these novel 5-HT1A receptor complexes offer new targets for treatment of depression.

Receptor–Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment

Directory of Open Access Journals (Sweden)

Dasiel O. Borroto-Escuela

2018-06-01

Full Text Available Due to the binding to a number of proteins to the receptor protomers in receptor heteromers in the brain, the term “heteroreceptor complexes” was introduced. A number of serotonin 5-HT1A heteroreceptor complexes were recently found to be linked to the ascending 5-HT pathways known to have a significant role in depression. The 5-HT1A–FGFR1 heteroreceptor complexes were involved in synergistically enhancing neuroplasticity in the hippocampus and in the dorsal raphe 5-HT nerve cells. The 5-HT1A protomer significantly increased FGFR1 protomer signaling in wild-type rats. Disturbances in the 5-HT1A–FGFR1 heteroreceptor complexes in the raphe-hippocampal 5-HT system were found in a genetic rat model of depression (Flinders sensitive line (FSL rats. Deficits in FSL rats were observed in the ability of combined FGFR1 and 5-HT1A agonist cotreatment to produce antidepressant-like effects. It may in part reflect a failure of FGFR1 treatment to uncouple the 5-HT1A postjunctional receptors and autoreceptors from the hippocampal and dorsal raphe GIRK channels, respectively. This may result in maintained inhibition of hippocampal pyramidal nerve cell and dorsal raphe 5-HT nerve cell firing. Also, 5-HT1A–5-HT2A isoreceptor complexes were recently demonstrated to exist in the hippocampus and limbic cortex. They may play a role in depression through an ability of 5-HT2A protomer signaling to inhibit the 5-HT1A protomer recognition and signaling. Finally, galanin (1–15 was reported to enhance the antidepressant effects of fluoxetine through the putative formation of GalR1–GalR2–5-HT1A heteroreceptor complexes. Taken together, these novel 5-HT1A receptor complexes offer new targets for treatment of depression.

Effects of chronic treatment with escitalopram or citalopram on extracellular 5-HT in the prefrontal cortex of rats: role of 5-HT1A receptors

Science.gov (United States)

Ceglia, I; Acconcia, S; Fracasso, C; Colovic, M; Caccia, S; Invernizzi, R W

2004-01-01

Microdialysis was used to study the acute and chronic effects of escitalopram (S-citalopram; ESCIT) and chronic citalopram (CIT), together with the 5-HT1A receptor antagonist WAY100,635 (N-[2-[methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide trihydrochloride) and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on extracellular 5-hydroxytryptamine (5-HT) levels in the rat prefrontal cortex. Extracellular 5-HT rose to 234 and 298% of basal values after subcutaneous (s.c.) acute doses of 0.15 and 0.63 mg kg−1 ESCIT. No further increase was observed at 2.5 mg kg−1 ESCIT (290%). The effect of 13-day s.c. infusion of 10 mg kg−1day−1 ESCIT on extracellular 5-HT (422% of baseline) was greater than after 2 days (257% of baseline), whereas exposure to ESCIT was similar. In contrast, the increase in extracellular 5-HT induced by the infusion of CIT for 2 (306%) and 13 days (302%) was similar. However, brain and plasma levels of S-citalopram in rats infused with CIT for 13 days were lower than after 2 days. Acute treatment with 2.5 mg kg−1 ESCIT or 5 mg kg−1 CIT raised extracellular 5-HT by 243 and 276%, respectively, in rats given chronic vehicle but had no effect in rats given ESCIT (10 mg kg−1 day−1) or CIT (20 mg kg−1 day−1) for 2 or 13 days, suggesting that the infused doses had maximally increased extracellular 5-HT. WAY100,635 (0.1 mg kg−1 s.c.) increased extracellular 5-HT levels by 168, 174 and 169% of prechallenge values in rats infused with vehicle or ESCIT for 2 or 13 days, respectively. WAY100,635 enhanced extracellular 5-HT levels to 226, 153 and 164% of prechallenge values in rats infused with vehicle or CIT for 2 and 13 days, respectively. 8-OH-DPAT (0.025 mg kg−1) reduced extracellular 5-HT by 54% in control rats, but had no effect in those given ESCIT and CIT for 13 days. This series of experiments led to the conclusion that chronic treatment with ESCIT desensitizes the 5-HT1A

Gender and the use of hormonal contraception in women are not associated with cerebral cortical 5-HT 2A receptor binding

DEFF Research Database (Denmark)

Frokjaer, V G; Erritzoe, D; Madsen, J

2009-01-01

to frontolimbic 5-HT(2A) receptor binding and to be more pronounced in women, again, the effect of gender was not significant (P=0.42, n=127). Also, the use of hormonal contraception (n=14) within the group of pre-menopausal women (total n=29) was not associated with cortical 5-HT(2A) receptor binding (P=0.......31). In conclusion, neither gender, nor the use of hormonal contraception in premenopausal women was associated with cortical 5-HT(2A) receptor binding....... binding it is not clear if gender or use of hormonal contraception exhibits associations with 5-HT(2A) receptor binding. We found no significant effect of gender on cortical 5-HT(2A) receptor binding (P=0.15, n=132). When adjusting for the personality trait neuroticism, known to be positively correlated...

The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors.

Science.gov (United States)

De Gregorio, Danilo; Posa, Luca; Ochoa-Sanchez, Rafael; McLaughlin, Ryan; Maione, Sabatino; Comai, Stefano; Gobbi, Gabriella

2016-11-01

d-lysergic diethylamide (LSD) is a hallucinogenic drug that interacts with the serotonin (5-HT) system binding to 5-HT 1 and 5-HT 2 receptors. Little is known about its potential interactions with the dopamine (DA) neurons of the ventral tegmental area (VTA). Using in-vivo electrophysiology in male adult rats, we evaluated the effects of cumulative doses of LSD on VTA DA neuronal activity, compared these effects to those produced on 5-HT neurons in the dorsal raphe nucleus (DRN), and attempted to identify the mechanism of action mediating the effects of LSD on VTA DA neurons. LSD, at low doses (5-20μg/kg, i.v.) induced a significant decrease of DRN 5-HT firing activity through 5-HT 2A and D 2 receptors. At these low doses, LSD did not alter VTA DA neuronal activity. On the contrary, at higher doses (30-120μg/kg, i.v.), LSD dose-dependently decreased VTA DA firing activity. The depletion of 5-HT with p-chlorophenylalanine did not modulate the effects of LSD on DA firing activity. The inhibitory effects of LSD on VTA DA firing activity were prevented by the D 2 receptor antagonist haloperidol (50μg/kg, i.v.) and by the 5-HT 1A receptor antagonist WAY-100,635 (500μg/kg, i.v.). Notably, pretreatment with the trace amine-associate receptor 1 (TAAR 1 ) antagonist EPPTB (5mg/kg, i.v.) blocked the inhibitory effect of LSD on VTA DA neurons. These results suggest that LSD at high doses strongly affects DA mesolimbic neuronal activity in a 5-HT independent manner and with a pleiotropic mechanism of action involving 5-HT 1A, D 2 and TAAR 1 receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers

DEFF Research Database (Denmark)

Ettrup, Anders; Hansen, Martin; Santini, Martin A

2011-01-01

Positron emission tomography (PET) imaging of serotonin 2A (5-HT(2A)) receptors with agonist tracers holds promise for the selective labelling of 5-HT(2A) receptors in their high-affinity state. We have previously validated [(11)C]Cimbi-5 and found that it is a 5-HT(2A) receptor agonist PET tracer....... In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [(11)C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT(2A) receptor agonist PET tracers in the pig...

Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT2A agonist PET tracers

DEFF Research Database (Denmark)

Ettrup, Anders; Hansen, Martin; Santini, Martin A

2011-01-01

Positron emission tomography (PET) imaging of serotonin 2A (5-HT(2A)) receptors with agonist tracers holds promise for the selective labelling of 5-HT(2A) receptors in their high-affinity state. We have previously validated [(11)C]Cimbi-5 and found that it is a 5-HT(2A) receptor agonist PET tracer....... In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [(11)C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT(2A) receptor agonist PET tracers in the pig...

2-D Imaging of Electron Temperature in Tokamak Plasmas

International Nuclear Information System (INIS)

Munsat, T.; Mazzucato, E.; Park, H.; Domier, C.W.; Johnson, M.; Luhmann, N.C. Jr.; Wang, J.; Xia, Z.; Classen, I.G.J.; Donne, A.J.H.; Pol, M.J. van de

2004-01-01

By taking advantage of recent developments in millimeter wave imaging technology, an Electron Cyclotron Emission Imaging (ECEI) instrument, capable of simultaneously measuring 128 channels of localized electron temperature over a 2-D map in the poloidal plane, has been developed for the TEXTOR tokamak. Data from the new instrument, detailing the MHD activity associated with a sawtooth crash, is presented

Tokamak experiments

International Nuclear Information System (INIS)

Robinson, D.C.

1987-01-01

With the advent of the new large tokamaks JET, JT-60 and TFTR important advances in magnetic confinement have been made. These include the exploitation of radio frequency and neutral beam heating on a much larger scale than previously, the demonstration of regimes of improved confinement and the demonstration of current drive at the Megamp level. A number of small and medium sized tokamaks have also come into operation recently such as WT-3 in Japan with an emphasis on radio frequency current drive and HL-1 a medium sized tokamak in China. Each of these new tokamaks is addressing specific problems which remain for the future development of the system. Of these particular problems: β, density and q limits remain important issues for the future development of the tokamak. β limits are being addressed on the DIII-D device in the USA. The anomalous confinement that the tokamak displays is being explored in detail on the TEXT device in the USA. Two other problems are impurity control and current drive. There is significant emphasis on divertor configurations at the present time with their enhanced confinement in the so called H mode. Due to improved discharge cleaning techniques and the ability to repetitively refuel using pellets, purer plasmas can be obtained even without divertors. Current drive remains a crucial issue for quasi of near steady state operation of the tokamak in the future and many current drive schemes are being investigated. (author) [pt

Comparison between 2D turbulence model ESEL and experimental data from AUG and COMPASS tokamaks

DEFF Research Database (Denmark)

Ondac, Peter; Horacek, Jan; Seidl, Jakub

2015-01-01

In this article we have used the 2D fluid turbulence numerical model, ESEL, to simulate turbulent transport in edge tokamak plasma. Basic plasma parameters from the ASDEX Upgrade and COMPASS tokamaks are used as input for the model, and the output is compared with experimental observations obtain...... for an extension of the ESEL model from 2D to 3D to fully resolve the parallel dynamics, and the coupling from the plasma to the sheath....

T-2 toxin and HT-2 toxin in grain and grain-based commodities in Europe: occurrence, factors affecting occurrence, co-occurence and toxicological effects

NARCIS (Netherlands)

Fels-Klerx, van der H.J.; Stratakou, I.

2010-01-01

This paper presents an overview of the occurrence of T-2 toxin and HT-2 toxin in cereals in Europe and derived food products, factors influencing the occurrence, co-occurrence with other trichothecenes, and toxicological effects of T-2 and HT-2 in human. Of all cereals, oats showed to be most

Gut satiety hormones cholecystokinin and glucagon-like Peptide-17-36 amide mediate anorexia induction by trichothecenes T-2 toxin, HT-2 toxin, diacetoxyscirpenol and neosolaniol.

Science.gov (United States)

Zhang, Jie; Liu, Shengli; Zhang, Hua; Li, Yuanyuan; Wu, Wenda; Zhang, Haibin

2017-11-15

The food-borne trichothecene mycotoxins have been documented to cause human and animal food poisoning. Anorexia is a hallmark of the trichothecene mycotoxins-induced adverse effects. Type B trichothecenes have been previously demonstrated to elicit robust anorectic responses, and this response has been directly linked to secretion of the gut satiety hormones cholecystokinin (CCK) and glucagon-like peptide-1 7-36 amide (GLP-1). However, less is known about the anorectic effects and underlying mechanisms of the type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), neosolaniol (NEO). The purpose of this study was to relate type A trichothecenes T-2, HT-2, DAS and NEO-induced anorectic response to changes plasma concentrations of CCK and GLP-1. Following both oral gavage and intraperitoneal (IP) administration of 1mg/kg bw T-2, HT-2, DAS and NEO evoked robust anorectic response and secretion of CCK and GLP-1. Elevations of plasma CCK markedly corresponded to anorexia induction by T-2, HT-2, DAS and NEO. Following oral exposure, plasma CCK was peaked at 6h, 6h, 2h, 2h and lasted up to 24h, 24h, > 6h, > 6h for T-2, HT-2, DAS and NEO, respectively. IP exposed to four toxins all induced elevation of CCK with peak point and duration at 6h and >24h, respectively. In contrast to CCK, GLP-1 was moderately elevated by these toxins. Following both oral and IP exposure, T-2 and HT-2 evoked plasma GLP-1 elevation with peak point and duration at 2h and 6h, respectively. Plasma GLP-1 was peaked at 2h and still increased at 6h for IP and oral administration with DAS and NEO, respectively. In conclusion, CCK plays a contributory role in anorexia induction but GLP-1 might play a lesser role in this response. Copyright © 2017 Elsevier Inc. All rights reserved.

Modelling dust transport in tokamaks

International Nuclear Information System (INIS)

Martin, J.D.; Martin, J.D.; Bacharis, M.; Coppins, M.; Counsell, G.F.; Allen, J.E.; Counsell, G.F.

2008-01-01

The DTOKS code, which models dust transport through tokamak plasmas, is described. The floating potential and charge of a dust grain in a plasma and the fluxes of energy to and from it are calculated. From this model, the temperature of the dust grain can be estimated. A plasma background is supplied by a standard tokamak edge modelling code (B2SOLPS5.0), and dust transport through MAST (the Mega-Amp Spherical Tokamak) and ITER plasmas is presented. We conclude that micron-radius tungsten dust can reach the separatrix in ITER. (authors)

5-HT3 and 5-HT4 antagonists inhibit peristaltic contractions in guinea-pig distal colon by mechanisms independent of endogenous 5-HT

Directory of Open Access Journals (Sweden)

Tiong Cheng Sia

2013-08-01

Full Text Available Recent studies have shown that endogenous serotonin is not required for colonic peristalsis in vitro, nor gastrointestinal (GI transit in vivo. However, antagonists of 5-Hydroxytryptamine (5-HT receptors can inhibit peristalsis and GI-transit in mammals, including humans. This raises the question of how these antagonists inhibit GI-motility and transit, if depletion of endogenous 5-HT does not cause any significant inhibitory changes to either GI-motility or transit ? We investigated the mechanism by which 5-HT3 and 5-HT4 antagonists inhibit distension-evoked peristaltic contractions in guinea-pig distal colon. In control animals, repetitive peristaltic contractions of the circular muscle were evoked in response to fixed fecal pellet distension. Distension-evoked peristaltic contractions were unaffected in animals with mucosa and submucosal plexus removed, that were also treated with reserpine (to deplete neuronal 5-HT. In control animals, peristaltic contractions were blocked temporarily by ondansetron (1-10µM and SDZ-205-557 (1-10µM in many animals. Interestingly, after this temporary blockade, and whilst in the continued presence of these antagonists, peristaltic contractions recovered, with characteristics no different from controls. Surprisingly, similar effects were seen in mucosa-free preparations, which had no detectable 5-HT, as detected by mass spectrometry. In summary, distension-evoked peristaltic reflex contractions of the circular muscle layer of the guinea-pig colon can be inhibited temporarily, or permanently, in the same preparation by selective 5-HT3 and 5-HT4 antagonists, depending on the concentration of the antagonists applied. These effects also occur in preparations that lack any detectable 5-HT. We suggest caution should be exercised when interpreting the effects of 5-HT3 and 5-HT4 antagonists; and the role of endogenous 5-HT, in the generation of distension-evoked colonic peristalsis.

Pharmacological and genetic interventions in serotonin (5-HT)(2C) receptors to alter drug abuse and dependence processes

NARCIS (Netherlands)

Filip, Malgorzata; Spampinato, Umberto; McCreary, Andrew C.; Przegalinski, Edmund

2012-01-01

The present review provides an overview on serotonin (5-hydroxytryptamine; 5-HT)(2C) receptors and their relationship to drug dependence. We have focused our discussion on the impact of 5-HT2C receptors on the effects of different classes of addictive drugs, illustrated by reference to data using

Structural characterisation of Arquad 2HT-75 organobentonites: Surface charge characteristics and environmental application

Energy Technology Data Exchange (ETDEWEB)

Sarkar, Binoy; Megharaj, Mallavarapu; Xi, Yunfei [CERAR - Centre for Environmental Risk Assessment and Remediation, Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); CRC CARE - Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, P.O. Box 486, Salisbury, SA 5106 (Australia); Naidu, Ravi, E-mail: ravi.naidu@crccare.com [CERAR - Centre for Environmental Risk Assessment and Remediation, Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); CRC CARE - Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, P.O. Box 486, Salisbury, SA 5106 (Australia)

2011-11-15

Highlights: {yields} Arquad 2HT-75 is comparatively less toxic and inexpensive surfactant. {yields} Increasing Arquad 2HT-75 loadings give rise to various organobentonite structures. {yields} The organobentonites produce positive zeta potential at TOC contents above 28.1%. {yields} Zeta potential values decrease with increasing suspension pH. {yields} Multiple mechanisms of partitioning, physio-sorption and chemisorption control adsorption. - Abstract: Organoclays are increasingly being used to remediate both contaminated soils and waste water. The present study was attempted to elucidate the structural evolution of bentonite based organoclays prepared from a commercially available, low-cost alkyl ammonium surfactant Arquad 2HT-75. XRD, FTIR, SEM and zeta potential measurement were used to characterise the organoclays. In particular, the relationship between surface charge characteristics of the organoclays and their ability to remediate organic contaminants such as phenol and p-nitrophenol was investigated. The investigation revealed that the arrangement and conformation of surfactant molecules in the bentonite became more regular, ordered and solid-like as of Arquad 2HT-75 loading increased. This also led to the formation of a positive zeta potential on the surface of organobentonites prepared with 3.57:1 and 4.75:1 surfactant-clay (w/w) ratio. The zeta potential values decreased with increasing pH of the suspension. The adsorption data of phenol and p-nitrophenol were best fitted to Freundlich isotherm model. The adsorption was controlled by multiple mechanisms of partitioning, physico-sorption and chemisorption. The outcomes of this study are useful for the synthesis of low cost organobentonite adsorbents for the remediation of ionisable organic contaminants such as phenol and p-nitrophenol from waste water.

5-HT causes splanchnic venodilation.

Science.gov (United States)

Seitz, Bridget M; Orer, Hakan S; Krieger-Burke, Teresa; Darios, Emma S; Thompson, Janice M; Fink, Gregory D; Watts, Stephanie W

2017-09-01

Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT 7 receptor. As part of studies designed to identify the mechanism(s) through which chronic (≥24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT 7 receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT 1/7 receptor agonist 5-carboxamidotryptamine; relaxation was abolished by the 5-HT 7 receptor antagonist SB-269970. Western blot analyses showed that the abdominal inferior vena cava and portal vein express 5-HT 7 receptor protein. In contrast, the thoracic vena cava, outside the splanchnic circulation, did not relax to serotonergic agonists and exhibited minimal expression of the 5-HT 7 receptor. Male Sprague-Dawley rats with chronically implanted radiotelemetry transmitters underwent repeated ultrasound imaging of abdominal vessels. After baseline imaging, minipumps containing vehicle (saline) or 5-HT (25 μg·kg -1 ·min -1 ) were implanted. Twenty-four hours later, venous diameters were increased in rats with 5-HT-infusion (percent increase from baseline: superior mesenteric vein, 17.5 ± 1.9; portal vein, 17.7 ± 1.8; and abdominal inferior vena cava, 46.9 ± 8.0) while arterial pressure was decreased (~13 mmHg). Measures returned to baseline after infusion termination. In a separate group of animals, treatment with SB-269970 (3 mg/kg iv) prevented the splanchnic venodilation and fall in blood pressure during 24 h of 5-HT infusion. Thus, 5-HT causes 5-HT 7 receptor-dependent splanchnic venous dilation associated with a fall in blood pressure. NEW & NOTEWORTHY This research is noteworthy because it combines and links, through the 5-HT 7 receptor, an in vitro observation (venorelaxation) with in vivo events

The binding characteristics and orientation of a novel radioligand with distinct properties at 5-HT3A and 5-HT3AB receptors

NARCIS (Netherlands)

Thompson, Andrew J; Verheij, Mark H P; Verbeek, Joost; Windhorst, Albert D; de Esch, Iwan J P; Lummis, Sarah C R

2014-01-01

VUF10166 (2-chloro-3-(4-methyl piperazin-1-yl)quinoxaline) is a ligand that binds with high affinity to 5-HT3 receptors. Here we synthesise [(3)H]VUF10166 and characterise its binding properties at 5-HT3A and 5-HT3AB receptors. At 5-HT3A receptors [(3)H]VUF10166 displayed saturable binding with a Kd

The 5-HT2A/1A agonist psilocybin disrupts modal object completion associated with visual hallucinations.

Science.gov (United States)

Kometer, Michael; Cahn, B Rael; Andel, David; Carter, Olivia L; Vollenweider, Franz X

2011-03-01

Recent findings suggest that the serotonergic system and particularly the 5-HT2A/1A receptors are implicated in visual processing and possibly the pathophysiology of visual disturbances including hallucinations in schizophrenia and Parkinson's disease. To investigate the role of 5-HT2A/1A receptors in visual processing the effect of the hallucinogenic 5-HT2A/1A agonist psilocybin (125 and 250 μg/kg vs. placebo) on the spatiotemporal dynamics of modal object completion was assessed in normal volunteers (n = 17) using visual evoked potential recordings in conjunction with topographic-mapping and source analysis. These effects were then considered in relation to the subjective intensity of psilocybin-induced visual hallucinations quantified by psychometric measurement. Psilocybin dose-dependently decreased the N170 and, in contrast, slightly enhanced the P1 component selectively over occipital electrode sites. The decrease of the N170 was most apparent during the processing of incomplete object figures. Moreover, during the time period of the N170, the overall reduction of the activation in the right extrastriate and posterior parietal areas correlated positively with the intensity of visual hallucinations. These results suggest a central role of the 5-HT2A/1A-receptors in the modulation of visual processing. Specifically, a reduced N170 component was identified as potentially reflecting a key process of 5-HT2A/1A receptor-mediated visual hallucinations and aberrant modal object completion potential. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Tokamak engineering mechanics

International Nuclear Information System (INIS)

Song, Yuntao; Wu, Weiyue; Du, Shijun

2014-01-01

Provides a systematic introduction to tokamaks in engineering mechanics. Includes design guides based on full mechanical analysis, which makes it possible to accurately predict load capacity and temperature increases. Presents comprehensive information on important design factors involving materials. Covers the latest advances in and up-to-date references on tokamak devices. Numerous examples reinforce the understanding of concepts and provide procedures for design. Tokamak Engineering Mechanics offers concise and thorough coverage of engineering mechanics theory and application for tokamaks, and the material is reinforced by numerous examples. Chapter topics include general principles, static mechanics, dynamic mechanics, thermal fluid mechanics and multiphysics structural mechanics of tokamak structure analysis. The theoretical principle of the design and the methods of the analysis for various components and load conditions are presented, while the latest engineering technologies are also introduced. The book will provide readers involved in the study of mechanical/fusion engineering with a general understanding of tokamak engineering mechanics.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

Directory of Open Access Journals (Sweden)

Xavier Viñals

2015-07-01

Full Text Available Activation of cannabinoid CB1 receptors (CB1R by delta9-tetrahydrocannabinol (THC produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

Science.gov (United States)

Viñals, Xavier; Moreno, Estefanía; Lanfumey, Laurence; Cordomí, Arnau; Pastor, Antoni; de La Torre, Rafael; Gasperini, Paola; Navarro, Gemma; Howell, Lesley A; Pardo, Leonardo; Lluís, Carmen; Canela, Enric I; McCormick, Peter J; Maldonado, Rafael; Robledo, Patricia

2015-07-01

Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

Interaction of cruciferin-based nanoparticles with Caco-2 cells and Caco-2/HT29-MTX co-cultures.

Science.gov (United States)

Akbari, Ali; Lavasanifar, Afsaneh; Wu, Jianping

2017-12-01

The objective of this work was to assess the potential of Cruciferin/Calcium (Cru/Ca) and Cruciferin/Chitosan (Cru/Cs) nanoparticles for oral drug delivery. For this purpose, Cru/Ca and Cru/Cs nanoparticles were developed through cold gelation of Cruciferin, a major canola protein, and in interaction with calcium and chitosan, respectively. The extent and rate of particle uptake in Caco-2 cells and Caco-2/HT29 co-culture was then evaluated by fluorescence spectroscopy as well as flow cytometry. Through pre-incubation of Caco-2 cell monolayer with specific endocytosis inhibitors, the mechanism of cell uptake was investigated. Our results showed that the uptake of negatively-charged Cru/Ca particles to be ∼3 times higher than positively-charged Cru/Cs ones by Caco-2 cells. Presence of mucus secreted by HT29 cells in their co-culture with Caco-2 had negligible influence on the uptake and transport of both particles. In contrast to Cru/Ca particles which were dissociated in the simulated gastrointestinal conditions, digestion of Cru/Cs particles resulted in 6- and 2-fold increase in the cellular uptake and transport of encapsulated coumarin in the latter particles, respectively. While the presence of mucus in Caco-2/HT29 co-culture caused 40-50% decrease of cellular uptake and transport for coumarin encapsulated in digested Cru/Cs particles, it had no significant effect on the cell uptake and transport of coumarin associated with Cru/Ca particles after digestion. Energy-dependent mechanisms were the dominant mechanism for uptake of both undigested and digested particles. Therefore, in Caco-2/HT29 co-culture which closely simulated intestinal epithelial cells, undigested Cru/Ca and Cru/Cs particles had the ability to penetrate mucus layers, while digested Cru/Cs particles showed mucoadhesive property, and digested Cru/Ca particles were dissociated. Our results points to a potential for cruciferin based nanoparticles for oral drug delivery. The long-term objective of

The Antidepressant 5-HT2A Receptor Antagonists Pizotifen and Cyproheptadine Inhibit Serotonin-Enhanced Platelet Function

Science.gov (United States)

Lin, Olivia A.; Karim, Zubair A.; Vemana, Hari Priya; Espinosa, Enma V. P.; Khasawneh, Fadi T.

2014-01-01

There is considerable interest in defining new agents or targets for antithrombotic purposes. The 5-HT2A receptor is a G-protein coupled receptor (GPCR) expressed on many cell types, and a known therapeutic target for many disease states. This serotonin receptor is also known to regulate platelet function. Thus, in our FDA-approved drug repurposing efforts, we investigated the antiplatelet activity of cyproheptadine and pizotifen, two antidepressant 5-HT2A Receptor antagonists. Our results revealed that cyproheptadine and pizotifen reversed serotonin-enhanced ADP-induced platelet aggregation in vitro and ex vivo. And the inhibitory effects of these two agents were found to be similar to that of EMD 281014, a 5-HT2A Receptor antagonist under development. In separate experiments, our studies revealed that these 5-HT2A receptor antagonists have the capacity to reduce serotonin-enhanced ADP-induced elevation in intracellular calcium levels and tyrosine phosphorylation. Using flow cytometry, we also observed that cyproheptadine, pizotifen, and EMD 281014 inhibited serotonin-enhanced ADP-induced phosphatidylserine (PS) exposure, P-selectin expression, and glycoprotein IIb-IIIa activation. Furthermore, using a carotid artery thrombosis model, these agents prolonged the time for thrombotic occlusion in mice in vivo. Finally, the tail-bleeding time was investigated to assess the effect of cyproheptadine and pizotifen on hemostasis. Our findings indicated prolonged bleeding time in both cyproheptadine- and pizotifen-treated mice. Notably, the increases in occlusion and bleeding times associated with these two agents were comparable to that of EMD 281014, and to clopidogrel, a commonly used antiplatelet drug, again, in a fashion comparable to clopidogrel and EMD 281014. Collectively, our data indicate that the antidepressant 5-HT2A antagonists, cyproheptadine and pizotifen do exert antiplatelet and thromboprotective effects, but similar to clopidogrel and EMD 281014, their

Role of Peptide YY3-36 and Glucose-Dependent Insulinotropic Polypeptide in Anorexia Induction by Trichothecences T-2 Toxin, HT-2 Toxin, Diacetoxyscirpenol, and Neosolaniol.

Science.gov (United States)

Zhang, Jie; Jia, Hui; Wang, Qingqing; Zhang, Yajie; Wu, Wenda; Zhang, Haibin

2017-09-01

Trichothecences, secondary metabolites produced by Fusarium, are serious health risks to humans and animals worldwide. Although type A trichothecence-induced food refusal has been observed, the mechanism underlying the anorexia caused by these compounds is not fully understood. In this study, we hypothesized that anorexia induced by type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), and neosolaniol (NEO), in mice corresponds to the changes in the gut satiety hormones peptide YY3-36 (PYY3-36) and glucose-dependent insulinotropic polypeptide (GIP) in plasma. A well-characterized mouse food refusal model was used in this assay. Oral exposure to or intraperitoneal (ip) injection of 1 mg/kg bw T-2, HT-2, DAS, or NEO resulted in dramatically decreased food intake, and PYY3-36 and GIP concentrations were elevated accordingly. Specifically, the PYY3-36 and GIP concentrations peaked at 2 h following oral exposure to these 4 toxins individually, although the durations were not identical. After ip administration of T-2 or HT-2, PYY3-36 significantly increased within 6 h. However, no significant difference was found in the DAS and NEO groups. The GIP levels peaked within 2, 2, 0.5, and 0.5 h, respectively, and remained increased up to 6, 6, 2, and 6 h, respectively, following T-2, HT-2, DAS, or NEO ip exposure. The increase in GIP was greater than that of PYY3-36 after exposure to the 4 toxins using 2 administration routes. Together, these findings suggest that PYY3-36 and GIP play a role in T-2-, HT-2-, DAS-, and NEO-induced anorexia. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Tokamak concept innovations

International Nuclear Information System (INIS)

1986-04-01

This document contains the results of the IAEA Specialists' Meeting on Tokamak Concept Innovations held 13-17 January 1986 in Vienna. Although it is the most advanced fusion reactor concept the tokamak is not without its problems. Most of these problems should be solved within the ongoing R and D studies for the next generation of tokamaks. Emphasis for this meeting was placed on innovations that would lead to substantial improvements in a tokamak reactor, even if they involved a radical departure from present thinking

Perfecting of shielding calculation technique against the gamma rays arising from a Tokamak with the TFR experience. Application to the conceptual design Tokamak TORE 2 SUPRA

International Nuclear Information System (INIS)

Diop, Cheikh M'Backe.

1980-09-01

The conception of the necessary shielding around a conceptual design Tokamak requires to execute an estimated calculation of the doses due to the different radiation sources arising from the machine: the thermonuclear neutron source and the gamma ray source emitted during the interaction of the runaway electrons with the diaphragm. In this study, we propose a theorical method to calculate this gamma source. We tackle also the shielding problem of the conceptual design Tokamak: TORE 2 SUPRA [fr

A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice.

Directory of Open Access Journals (Sweden)

Yvonne Couch

Full Text Available It is well documented that serotonin (5-HT plays an important role in psychiatric illness. For example, myalgic encephalomyelitis (ME/CFS, which is often provoked by infection, is a disabling illness with an unknown aetiology and diagnosis is based on symptom-specific criteria. However, 5-HT2A receptor expression and peripheral cytokines are known to be upregulated in ME. We sought to examine the relationship between the 5-HT system and cytokine expression following systemic bacterial endotoxin challenge (LPS, 0.5 mg/kg i.p., at a time when the acute sickness behaviours have largely resolved. At 24 hours post-injection mice exhibit no overt changes in locomotor behaviour, but do show increased immobility in a forced swim test, as well as decreased sucrose preference and reduced marble burying activity, indicating a depressive-like state. While peripheral IDO activity was increased after LPS challenge, central activity levels remained stable and there was no change in total brain 5-HT levels or 5-HIAA/5-HT. However, within the brain, levels of TNF and 5-HT2A receptor mRNA within various regions increased significantly. This increase in receptor expression is reflected by an increase in the functional response of the 5-HT2A receptor to agonist, DOI. These data suggest that regulation of fatigue and depressive-like moods after episodes of systemic inflammation may be regulated by changes in 5-HT receptor expression, rather than by levels of enzyme activity or cytokine expression in the CNS.

A non-linear model for temperature-dependent sporulation and T-2 and HT-2 production of Fusarium langsethiae and Fusarium sporotrichioides.

Science.gov (United States)

Nazari, Leyla; Manstretta, Valentina; Rossi, Vittorio

2016-04-01

This research has produced new quantitative data on the sporulation and T-2+HT-2 toxin production that could be further integrated to develop a comprehensive disease or toxin prediction model for Fusarium langsethiae and Fusarium sporotrichioides. Experiments were conducted to determine the effect of temperature or incubation time on sporulation and the effect of temperature on T-2+HT-2 toxin production of strains of the two species. F. sporotrichioides demonstrated a preference for higher temperatures than F. langsethiae during sporulation; the optimum temperature was 24.5 ± 0.7 °C for F. langsethiae and 32.3 ± 2.1 °C for F. sporotrichioides, according to the Beta equation fitted to the data. The dynamics of sporulation over different incubation times were fitted by a Gompertz function. The maximum spore production was estimated to be after 18 and 8 d incubation at optimum temperatures for F. langsethiae and F. sporotrichioides, respectively. F. sporotrichioides produced more T-2+HT-2 than F. langsethiae. The best fit of the effect of temperature on T-2+HT-2 production in wheat grains was obtained with a Beta equation showing an optimum temperature of 14.7 ± 0.8 °C for F. langsethiae and 12.1 ± 0.2 °C for F. sporotrichioides. The optimum temperature for mycotoxin production was lower than for sporulation. Copyright © 2016 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Texas Experimental Tokamak

International Nuclear Information System (INIS)

Wootton, A.J.

1993-04-01

This progress report covers the period from November 1, 1990 to April 30, 1993. During that period, TEXT was operated as a circular tokamak with a material limiter. It was devoted to the study of basic plasma physics, in particular to study of fluctuations, turbulence, and transport. The purpose is to operate and maintain TEXT Upgrade as a complete facility for applied tokamak physics, specifically to conduct a research program under the following main headings: (1) to elucidate the mechanisms of working gas, impurity, and thermal transport in tokamaks, in particular to understand the role of turbulence; (2) to study physics of the edge plasma, in particular the turbulence; (3) to study the physics or resonant magnetic fields (ergodic magnetic divertors, intra island pumping); and (4) to study the physics of electron cyclotron heating (ECRH). Results of studies in each of these areas are reported

Acquisition session length modulates consolidation effects produced by 5-HT2C ligands in a mouse autoshaping-operant procedure.

Science.gov (United States)

Walker, Ellen A; Foley, John J

2010-03-01

Although the neurotransmitter, 5-hydroxytryptamine (serotonin, 5-HT), has been implicated as a mediator of learning and memory, the specific role of 5-HT receptors in rodents requires further delineation. In this study, 5-HT2C receptor ligands of varying relative intrinsic efficacies were tested in a mouse learning and memory model called autoshaping-operant. On day 1, mice were placed in experimental chambers and presented with a tone on a variable interval schedule. The tone remained on for 6 s or until a nose-poke response occurred to produce a dipper with Ensure solution. Mice were then injected with saline, MK212 (full agonist), m-chlorophenylpiperazine (partial agonist), mianserin, and SB206 553 (inverse agonists), and methysergide and (+)-2-bromo lysergic acid diethylamide (+)-hydrogen tartrate (neutral antagonists). Each compound was injected after either 1 or 2-h acquisition sessions on day 1 to investigate the role of acquisition session length on consolidation. Day 1 injection of the 5-HT2C inverse agonist mianserin produced greater retrieval impairments of the autoshaped operant response on day 2 than any other agent tested. Furthermore, decreasing the length of the acquisition session to 1h significantly increased the difficulty of the autoshaping task further modulating the consolidation effects produced by the 5-HT2C ligands tested.

Joint research using small tokamaks

International Nuclear Information System (INIS)

Gryaznevich, M.P.; Bosco, E. Del; Malaquias, A.; Mank, G.; Oost, G. van; He, Yexi; Hegazy, H.; Hirose, A.; Hron, M.; Kuteev, B.; Ludwig, G.O.; Nascimento, I.C.; Silva, C.; Vorobyev, G.M.

2005-01-01

Small tokamaks have an important role in fusion research. More than 40 small tokamaks are operational. Research on small tokamaks has created a scientific basis for the scaling-up to larger tokamaks. Well-known scientific and engineering schools, which are now determining the main directions of fusion science and technology, have been established through research on small tokamaks. Combined efforts within a network of small and medium size tokamaks will further enhance the contribution of small tokamaks. A new concept of interactive coordinated research using small tokamaks in the mainstream fusion science areas, in testing of new diagnostics, materials and technologies as well as in education, training and broadening of the geography of fusion research in the scope of the IAEA Coordinated Research Project, is presented

Blockade of MK-801-induced heat shock protein 72/73 in rat brain by antipsychotic and monoaminergic agents targeting D2, 5-HT1A, 5-HT2A and α1-adrenergic receptors.

Science.gov (United States)

Romón, Tamara; Planas, Anna M; Adell, Albert

2014-02-01

Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists can produce positive and negative symptomatology as well as impairment of cognitive function that closely resemble those present in schizophrenia. In rats, these drugs induce a behavioral syndrome (characterized by hyperlocomotion and stereotypies), an enhanced glutamatergic transmission in the medial prefrontal cortex, and damage to retrosplenial cortical neurons in adult rats, which was measured as the induction of the stress protein 72/73 kDa heat shock protein (Hsp72/73). In the present work, we have examined the existence of possible differences among different antipsychotic drugs in their capacity to block immunolabeling of Hsp72/73 in the retrosplenial cortex of the rat induced by the potent NMDA receptor antagonist, MK- 801. In addition, the effects of selective monoaminergic agents were also studied to delineate the particular receptors responsible for the actions of antipsychotic drugs. Pretreatment with clozapine, chlorpromazine, olanzapine, ziprasidone--and to a lesser extent haloperidol-reduced the formation of Hsp72/73 protein in the rat retrosplenial cortex after the administration of MK-801. In addition, antagonism at dopamine D2 (raclopride), 5-HT2 (M100907) and α1- adrenoceptors (prazosin) as well as agonism at 5-HT1A receptors (BAY x 3702) also diminished the MK-801-induced number of cells labeled with Hsp72/73. Each of these effects may contribute to antipsychotic action. The results suggest that the efficacy of atypical antipsychotic drugs in the clinic may result from a combined effect on 5-HT2, 5-HT1A and α1-adrenergic receptors added to the classical dopamine D2 receptor antagonism.

Environmental HTO/HT sampler development

International Nuclear Information System (INIS)

Workman, W.J.G.; Brown, R.M.; Wood, M.J.

1994-01-01

Tests of retention by several drying agents of HTO from an air stream containing HT have been performed. Two batches of Molecular Sieve (MS) 4A retained up to 1.3% of HT passed through them, in contrast to material tested in 1986, when retention was -4 . Retention of 10 -5 to 10 -6 was observed for DRIERITE (anhydrous calcium sulphate) and Silica Gel. DRIERITE is preferred over Silica Gel as a desiccant in an air sampler for environmental HTO/HT, because it is much easier to decontaminate for reuse. An improved air sampler has been designed, 2 units constructed and components procured for 3 more. The air sampler may be line or battery operated, accommodates up to four 120 g drier or oxidizer traps, and will pump up to 4 L/min for up to 24 hours on battery power. It is built into a rugged aluminum case and weighs approximately 11 kg overall, facilitating deployment in the field. (author). 5 refs., 2 tabs., 4 figs

Joint research using small tokamaks

International Nuclear Information System (INIS)

Gryaznevich, M.P.; Del Bosco, E.; Malaquias, A.; Mank, G.; Oost, G. van

2005-01-01

Small tokamaks have an important role in fusion research. More than 40 small tokamaks are operational. Research on small tokamaks has created a scientific basis for the scaling-up to larger tokamaks. Well-known scientific and engineering schools, which are now determining the main directions of fusion science and technology, have been established through research on small tokamaks. Combined efforts within a network of small and medium size tokamaks will further enhance the contribution of small tokamaks. A new concept of interactive co-ordinated research using small tokamaks in the mainstream fusion science areas, in testing of new diagnostics, materials and technologies as well as in education, training and broadening of the geography of fusion research in the scope of the IAEA Co-ordinated Research Project is presented. (author)

Tokamak devices: towards controlled fusion

International Nuclear Information System (INIS)

Trocheris, M.

1975-01-01

The Tokamak family is from Soviet Union. These devices were exclusively studied at the Kurchatov Institute in Moscow for more than ten years. The first occidental Tokamak started in 1970 at Princeton. The TFR (Tokamak Fontenay-aux-Roses) was built to be superior to the Russian T4. Tokamak future is now represented by the JET (Joint European Tokamak) [fr

Identification of 5HT2-receptors on longitudinal muscle of the guinea pig ileum

International Nuclear Information System (INIS)

Engel, G.; Hoyer, D.; Kalkman, H.O.; Wick, M.B.

1984-01-01

In binding experiments with the radioligands [ 3 H]Ketanserin (HKet) and [ 125 I]LSD (ILSD) 21 compounds were investigated using rat brain cortex membranes. The pK/sub D/-values of the compounds were virtually independent of the radioligand used and their rank order was consistent with classification of the binding sites as being of the 5-HT 2 -type. In contrast, in the longitudinal muscle of the guinea pig ileum in the presence of 0.3 microM cinanserin, ILSD labelled sites which were quite different to those in the cortex. In a functional test antagonism of the 5HT induced contraction of the guinea-pig ileum was measured in the presence of 1 microM atropine. The pharmacological inhibition constants (IC 50 -values) of 8 compounds correlated well with the dissociation constants for HKet binding in the cortex and did not correlate with the data from ILSD binding in the guinea pig ileum. It is concluded that the ileum contains postjunctional 5HT 2 -receptors which mediate contraction. The nature of the ILSD binding sites in the ileum remains to be elucidated

Submillimeter wave propagation in tokamak plasmas

International Nuclear Information System (INIS)

Ma, C.H.; Hutchinson, D.P.; Staats, P.A.; Vander Sluis, K.L.; Mansfield, D.K.; Park, H.; Johnson, L.C.

1986-01-01

Propagation of submillimeter waves (smm) in tokamak plasma was investigated both theoretically and experimentally to ensure successful measurements of electron density and plasma current distributions in tokamak devices. Theoretical analyses were carried out to study the polarization of the smm waves in TFTR and ISX-B tokamaks. A multichord smm wave interferometer/polarimeter system was employed to simultaneously measure the line electron density and poloidal field-induced Faraday rotation in the ISX-B tokamak. The experimental study on TFTR is under way. Computer codes were developed and have been used to study the wave propagation and to reconstruct the distributions of plasma current and density from the measured data. The results are compared with other measurements. 5 references, 2 figures

Overview of the latest HT-7 experiments

International Nuclear Information System (INIS)

Wan Baonian; Luo Jiarong; Li Jiangang

2005-01-01

An overview of the HT-7 experimental progress during 2003-2004 is presented. The operational scenarios of H-mode, negative reversed shear (RS) and high l i were investigated for quasi-steady-state high performance plasma discharges. Stationary internal transport barriers (ITBs) with normalized performance β N *H 89 > 1-3 have been obtained with combined injection of lower hybrid (LH) and ion Bernstein (IB) waves for a duration of several hundred energy confinement times in weak negative reversed shear. The maximum fraction of non-inductive current was >90% I p . The increase of the total injected power up to 1 MW did not degrade the plasma confinement significantly in the RS operational scenario. Plasma performance and duration were mainly limited by two kinds of MHD instabilities and recycling. The high l i plasma was created by fast plasma current ramp-down and sustained by central LHCD and IBW heating for a duration of >1 s with a strongly peaked electron temperature profile. The highest central electron temperature obtained was as much as 4.5 keV. Stationary improved confinement has been observed in the high l i plasma. The longest plasma discharge, with a duration of 240 s, T e (0) ∼ 1 keV and a central electron density of >0.8 x 10 19 m -3 , was achieved in 2004. A fully LHW current driven plasma without using ohmic current in the central solenoid coils was sustained for 80 s. The main limitation for the pulse length was due to the recycling, which caused an uncontrollable rise in the electron density. The poloidal large-scale ExB time-varying flows, electrostatic and magnetic Reynolds stress were directly measured in the boundary plasma of the HT-7 tokamak. (author)

Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task.

Directory of Open Access Journals (Sweden)

Simon R O Nilsson

Full Text Available Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS-, in a T- or Y-maze configuration. This was followed by three conditions; (1 Full reversal, where contingencies reversed; (2 Perseverance, where the previous CS+ became CS- and the previous CS- was replaced by a novel CS+; (3 Learned non-reward, where the previous CS- became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss

Tokamak simulation code manual

International Nuclear Information System (INIS)

Chung, Moon Kyoo; Oh, Byung Hoon; Hong, Bong Keun; Lee, Kwang Won

1995-01-01

The method to use TSC (Tokamak Simulation Code) developed by Princeton plasma physics laboratory is illustrated. In KT-2 tokamak, time dependent simulation of axisymmetric toroidal plasma and vertical stability have to be taken into account in design phase using TSC. In this report physical modelling of TSC are described and examples of application in JAERI and SERI are illustrated, which will be useful when TSC is installed KAERI computer system. (Author) 15 refs., 6 figs., 3 tabs

Economic considerations of commercial tokamak options

International Nuclear Information System (INIS)

Dabiri, A.E.

1986-05-01

Systems studies have been performed to assess commercial tokamak options. Superconducting, as well as normal, magnet coils in either first or second stability regimes have been considered. A spherical torus (ST), as well as an elongated tokamak (ET), is included in the study. The cost of electricity (COE) is selected as the figure of merit, and beta and first-wall neutron wall loads are selected to represent the physics and technology characteristics of various options. The results indicate that an economical optimum for tokamaks is predicted to require a beta of around 10%, as predicted to be achieved in the second stability regime, and a wall load of about 5 MW/m 2 , which is assumed to be optimum technologically. This tokamak is expected to be competitive with fission plants if efficient, noninductive current drive is developed. However, if this regime cannot be attained, all other tokamaks operating in the first stability regime, including spherical torus and elongated tokamak and assuming a limiting wall load of 5 MW/m 2 , will compete with one another with a COE of about 50 mill/kWh. This 40% higher than the COE for the optimum reactor in the second stability regime with fast-wave current drive. The above conclusions pertain to a 1200-MW(e) net electric power plant. A comparison was also made between ST, ET, and superconducting magnets in the second stability regime with fast-wave current drive at 600 MW(e)

Plasma facing components design of KT-2 tokamak

International Nuclear Information System (INIS)

In, Sang Ryul; Yoon, Byung Joo; Song, Woo Soeb; Xu, Chao Yin

1997-04-01

The vacuum vessel of KT-2 tokamak is protected from high thermal loads by various kinds of plasma facing components (PFC): outer and inner divertors, neutral baffle, inboard limiter, poloidal limiter, movable limiter and passive plate, installed on the inner wall of the vessel. In this report the pre-engineering design of the plasma facing components, including design requirements and function, structures of PFC assemblies, configuration of cooling systems, calculations of some mechanical and hydraulic parameters, is presented. Pumping systems for the movable limiter and the divertor are also discussed briefly. (author). 49 figs

An immunocapture/scintillation proximity analysis of G alpha q/11 activation by native serotonin (5-HT)2A receptors in rat cortex: blockade by clozapine and mirtazapine.

Science.gov (United States)

Mannoury La Cour, C; Chaput, C; Touzard, M; Millan, M J

2009-02-01

Though transduction mechanisms recruited by heterologously expressed 5-HT(2A) receptors have been extensively studied, their interaction with specific subtypes of G-protein remains to be directly evaluated in cerebral tissue. Herein, as shown by an immunocapture/scintillation proximity analysis, 5-HT, the prototypical 5-HT(2A) agonist, DOI, and Ro60,0175 all enhanced [(35)S]GTPgammaS binding to G alpha q/11 in rat cortex with pEC(50) values of 6.22, 7.24 and 6.35, respectively. No activation of G o or G s/olf was seen at equivalent concentrations of DOI. Stimulation of G alpha q/11 by 5-HT (30 microM) and DOI (30 microM) was abolished by the selective 5-HT(2A) vs. 5-HT(2C)/5-HT(2B) antagonists, ketanserin (pK(B) values of 9.11 and 8.88, respectively) and MDL100,907 (9.82 and 9.68). By contrast, 5-HT-induced [(35)S]GTPgammaS binding to G alpha q/11 was only weakly inhibited by the preferential 5-HT(2C) receptor antagonists, RS102,221 (6.94) and SB242,084 (7.39), and the preferential 5-HT(2B) receptor antagonist, LY266,097 (6.66). The antipsychotic, clozapine, which had marked affinity for 5-HT(2A) receptors, blocked the recruitment of G alpha q/11 by 5-HT and DOI with pK(B) values of 8.54 and 8.14, respectively. Its actions were mimicked by the "atypical" antidepressant and 5-HT(2A) receptor antagonist, mirtazapine, which likewise blocked 5-HT and DOI-induced G alpha q/11 protein activation with pK(B) values of 7.90 and 7.76, respectively. In conclusion, by use of an immunocapture/scintillation proximity strategy, this study shows that native 5-HT(2A) receptors in rat frontal cortex specifically recruit G alpha q/11 and that this action is blocked by clozapine and mirtazapine. Quantification of 5-HT(2A) receptor-mediated G alpha q/11 activation in frontal cortex should prove instructive in characterizing the actions of diverse classes of psychotropic agent. 2008 Wiley-Liss, Inc.

Nuclear fusion research at Tokamak Energy Ltd

International Nuclear Information System (INIS)

Windridge, Melanie J.; Gryaznevich, Mikhail; Kingham, David

2017-01-01

Tokamak Energy's approach is close to the mainstream of nuclear fusion, and chooses a spherical tokamak, which is an economically developed form of Tokamak reactor design, as research subjects together with a high-temperature superconducting magnet. In the theoretical prediction, it is said that spherical tokamak can make tokamak reactor's scale compact compared with ITER or DEMO. The dependence of fusion energy multiplication factor on reactor size is small. According to model studies, it has been found that the center coil can be protected from heat and radiation damage even if the neutron shielding is optimized to 35 cm instead of 1 m. As a small tokamak with a high-temperature superconducting magnet, ST25 HTS, it demonstrated in 2015 continuous operation for more than 24 hours as a world record. Currently, this company is constructing a slightly larger ST40 type, and it is scheduled to start operation in 2017. ST40 is designed to demonstrate that it can realize a high magnetic field with a compact size and aims at attaining 8-10 keV (reaching the nuclear fusion reaction temperature at about 100 million degrees). This company will verify the startup and heating technology by the coalescence of spherical tokamak expected to have plasma current of 2 MA, and will also use 2 MW of neutral particle beam heating. In parallel with ST40, it is promoting a development program for high-temperature superconducting magnet. (A.O.)

Synthesis, radiofluorination, and preliminary evaluation of the potential 5-HT2A receptor agonists [18 F]Cimbi-92 and [18 F]Cimbi-150

DEFF Research Database (Denmark)

Edgar, Fraser Graeme; Hansen, Hanne D; Leth-Petersen, Sebastian

2017-01-01

An agonist PET tracer is of key interest for the imaging of the 5-HT2A receptor, as exemplified by the previously reported success of [11 C]Cimbi-36. Fluorine-18 holds several advantages over carbon-11, making it the radionuclide of choice for clinical purposes. In this respect, an 18 F-labelled ......An agonist PET tracer is of key interest for the imaging of the 5-HT2A receptor, as exemplified by the previously reported success of [11 C]Cimbi-36. Fluorine-18 holds several advantages over carbon-11, making it the radionuclide of choice for clinical purposes. In this respect, an 18 F......-labelled agonist 5-HT2A receptor (5-HT2A R) tracer is highly sought after. Herein, we report a 2-step, 1-pot labelling methodology of 2 tracer candidates. Both ligands display high in vitro affinities for the 5-HT2A R. The compounds were synthesised from easily accessible labelling precursors, and radiolabelled...

Phosphotidylinositol turnover in vascular, uterine, fundal, and tracheal smooth muscle: effect of serotonin (5HT)

International Nuclear Information System (INIS)

Cohen, M.L.; Wittenauer, L.A.

1986-01-01

In brain, platelets, and aorta, 5HT has been reported to increase phosphotidylinositol turnover, an effect linked to 5HT 2 receptors. The authors examined the effect of 5HT on 3 H-inositol-1-phosphate ( 3 H-I-P) in tissues possessing 5HT 2 receptors that mediate contraction to 5HT (rat jugular vein, aorta, uterus and guinea pig trachea) and in a tissue in which contraction to 5HT is not mediated by 5HT 2 receptors (rat stomach fundus). Tissues were incubated (37 0 C, 95% O 2 , 5% CO 2 ) with 3 H-inositol (90 min), washed, LiCl 2 (10 mM) and 5HT added for 90 min, extracted, and 3 H-I-P eluted from a Dowex-1 column. Basal 3 H-I-P was 10-fold higher in the uterus than in the other tissues. 5HT (10 -6 -10 -4 M) increased 3 H-I-P in the jugular vein, aorta, and uterus but not in the trachea or fundus. Maximum increase was greatest in the jugular vein (8-fold) with an ED 50 of 0.4 μM 5HT. The selective 5HT 2 receptor blocker, LY53857 (10 -8 M) antagonized the increase in 3 H-I-P by 5HT in the jugular vein, aorta and uterus. Pargyline (10 -5 M) added to the trachea and fundus did not unmask an effect of 5HT (10 -4 M). These data suggest that (1) the jugular vein produced the most sensitive response to 5HT-induced increases in 3 H-I-P, (2) increases in 3 H-I-P by 5HT in smooth muscle may be linked to 5HT 2 receptors and (3) activation of 5HT 2 receptors as occurred in the trachea will not always increase 3 H-I-P

Design of self-cooled, liquid-metal blankets for tokamak and tandem mirror reactors

International Nuclear Information System (INIS)

Cha, Y.S.; Gohar, Y.; Hassanein, A.M.; Majumdar, S.; Picologlou, B.F.; Smith, D.L.; Szo, D.K.

1985-01-01

Results of the self-cooled, liquid-metal blanket design from the Blanket Comparison and Selection Study (BCSS) are summarized. The objectives of the BCSS project are to define a small number (about three) of blanket concepts that should be the focus of the blanket research and development (RandD) program, identify and prioritize the critical issues for the leading blanket concepts, and provide technical input necessary to develop a blanket RandD program plan. Two liquid metals (lithium and lithium-lead (17Li-83Pb)) and three structural materials (primary candidate alloy (PCA), ferritic steel (FS) (HT-9), and vanadium alloy (V-15 Cr-5 Ti)) are included in the evaluations for both tokamaks and tandem mirror reactors (TMRs). TMR is of the tube configuration similar to the Mirror Advanced Reactor Study design. Analyses were performed in the following generic areas for each blanket concept: MHD, thermal hydraulics, stress, neutronics, and tritium recovery. Integral analyses were performed to determine the design window for each blanket design. The Li/Li/V blanket for tokamak and the Li/Li/V, LiPb/LiPb/V, and Li/Li/HT-9 blankets for the TMR are judged to be top-rated concepts. Because of its better thermophysical properties and more uniform nuclear heating profile, liquid lithium is a better coolant than liquid 17Li83Pb. From an engineering point of view, vanadium alloy is a better structural material than either FS or PCA since the former has both a higher allowable structural temperature and a higher allowable coolant/structure interface temperature than the latter. Critical feasibility issues and design constraints for the self-cooled, liquid-metal blanket concepts are identified and discussed

Regulation of Hippocampal 5-HT Release by P2X7 Receptors in Response to Optogenetic Stimulation of Median Raphe Terminals of Mice

Directory of Open Access Journals (Sweden)

Flóra Gölöncsér

2017-10-01

Full Text Available Serotonergic and glutamatergic neurons of median raphe region (MRR play a pivotal role in the modulation of affective and cognitive functions. These neurons synapse both onto themselves and remote cortical areas. P2X7 receptors (P2rx7 are ligand gated ion channels expressed by central presynaptic excitatory nerve terminals and involved in the regulation of neurotransmitter release. P2rx7s are implicated in various neuropsychiatric conditions such as schizophrenia and depression. Here we investigated whether 5-HT release released from the hippocampal terminals of MRR is subject to modulation by P2rx7s. To achieve this goal, an optogenetic approach was used to selectively activate subpopulation of serotonergic terminals derived from the MRR locally, and one of its target area, the hippocampus. Optogenetic activation of neurons in the MRR with 20 Hz was correlated with freezing and enhanced locomotor activity of freely moving mice and elevated extracellular levels of 5-HT, glutamate but not GABA in vivo. Similar optical stimulation (OS significantly increased [3H]5-HT and [3H]glutamate release in acute MRR and hippocampal slices. We examined spatial and temporal patterns of [3H]5-HT release and the interaction between the serotonin and glutamate systems. Whilst [3H]5-HT release from MRR neurons was [Ca2+]o-dependent and sensitive to TTX, CNQX and DL-AP-5, release from hippocampal terminals was not affected by the latter drugs. Hippocampal [3H]5-HT released by electrical but not OS was subject to modulation by 5- HT1B/D receptors agonist sumatriptan (1 μM, whereas the selective 5-HT1A agonist buspirone (0.1 μM was without effect. [3H]5-HT released by electrical and optical stimulation was decreased in mice genetically deficient in P2rx7s, and after perfusion with selective P2rx7 antagonists, JNJ-47965567 (0.1 μM, and AZ-10606120 (0.1 μM. Optical and electrical stimulation elevated the extracellular level of ATP. Our results demonstrate for the

Strain differences in basal and post-citalopram extracellular 5-HT in the mouse medial prefrontal cortex and dorsal hippocampus: relation with tryptophan hydroxylase-2 activity.

Science.gov (United States)

Calcagno, E; Canetta, A; Guzzetti, S; Cervo, L; Invernizzi, R W

2007-11-01

We used the microdialysis technique to compare basal extracellular serotonin (5-HT) and the response to citalopram in different strains of mice with functionally different allelic forms of tryptophan hydroxylase-2 (TPH-2), the rate-limiting enzyme in brain 5-HT synthesis. DBA/2J, DBA/2N and BALB/c mice carrying the 1473G allele of TPH-2 had less dialysate 5-HT in the medial prefrontal cortex and dorsal hippocampus (DH) (20-40% reduction) than C57BL/6J and C57BL/6N mice carrying the 1473C allele. Extracellular 5-HT estimated by the zero-net flux method confirmed the result of conventional microdialysis. Citalopram, 1.25, 5 and 20 mg/kg, dose-dependently raised extracellular 5-HT in the medial prefrontal cortex of C57BL/6J mice, with maximum effect at 5 mg/kg, but had significantly less effect in DBA/2J and BALB/c mice and in the DH of DBA/2J mice. A tryptophan (TRP) load enhanced basal extracellular 5-HT in the medial prefrontal cortex of DBA/2J mice but did not affect citalopram's ability to raise cortical and hippocampal extracellular 5-HT. The impairment of 5-HT synthesis quite likely accounts for the reduction of basal 5-HT and the citalopram-induced rise in mice carrying the mutated enzyme. These findings might explain why DBA/2 and BALB/c mice do not respond to citalopram in the forced swimming test. Although TRP could be a useful strategy to improve the antidepressant effect of citalopram (Cervo et al. 2005), particularly in subjects with low 5-HT synthesis, the contribution of serotonergic and non-serotonergic mechanisms to TRP's effect remains to be elucidated.

Comparison of anorectic potencies of the trichothecenes T-2 toxin, HT-2 toxin and satratoxin G to the ipecac alkaloid emetine

Directory of Open Access Journals (Sweden)

Wenda Wu

2015-01-01

Full Text Available Trichothecene mycotoxins, potent translational inhibitors that are associated with human food poisonings and damp-building illnesses, are of considerable concern to animal and human health. Food refusal is a hallmark of exposure of experimental animals to deoxynivalenol (DON and other Type B trichothecenes but less is known about the anorectic effects of foodborne Type A trichothecenes (e.g., T-2 toxin, HT-2 toxin, airborne Type D trichothecenes (e.g., satratoxin G [SG] or functionally analogous metabolites that impair protein synthesis. Here, we utilized a well-described mouse model of food intake to compare the anorectic potencies of T-2 toxin, HT-2 toxin, and SG to that of emetine, a medicinal alkaloid derived from ipecac that inhibits translation. Intraperitoneal (IP administration with T-2 toxin, HT-2 toxin, emetine and SG evoked anorectic responses that occurred within 0.5 h that lasted up to 96, 96, 3 and 96 h, respectively, with lowest observed adverse effect levels (LOAELs being 0.1, 0.1, 2.5 and 0.25 mg/kg BW, respectively. When delivered via natural routes of exposure, T-2 toxin, HT-2 toxin, emetine (oral and SG (intranasal induced anorectic responses that lasted up to 48, 48, 3 and 6 h, respectively with LOAELs being 0.1, 0.1, 0.25, and 0.5 mg/kg BW, respectively. All four compounds were generally much more potent than DON which was previously observed to have LOAELs of 1 and 2.5 mg/kg BW after IP and oral dosing, respectively. Taken together, these anorectic potency data will be valuable in discerning the relative risks from trichothecenes and other translational inhibitors of natural origin.

Data bank system in JFT-2M tokamak

International Nuclear Information System (INIS)

Takada, S.; Matsuda, T.; Miura, Y.; Mori, M.; Kawakami, T.; Matoba, T.

1987-01-01

It is very important to keep suitably and use effectively experimental data in the field of fusion research. The data bank system for fusion experiment can be classified into the following two forms, according to the type of their use: (1) Rapid Analysis Data Bank System; (2) High Quality Data Bank System. And their features are summarized. The data bank system of the former type was prepared for JFT-2M tokamak on the basis of the above classification. By introduction of this data bank system, the following results can be obtained: (1) Rationalization of data analyzing procedure; (2) Improvement of reliability by exclusion of bad data; (3) Easy expansions of analyzing function and tool development; (4) Space saving by extraction and compression of key information

Aromatic interactions impact ligand binding and function at serotonin 5-HT2C G protein-coupled receptors: receptor homology modelling, ligand docking, and molecular dynamics results validated by experimental studies

Science.gov (United States)

Córdova-Sintjago, Tania; Villa, Nancy; Fang, Lijuan; Booth, Raymond G.

2014-02-01

The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2 G protein-coupled receptor (GPCR) family consists of types 2A, 2B, and 2C that share ∼75% transmembrane (TM) sequence identity. Agonists for 5-HT2C receptors are under development for psychoses; whereas, at 5-HT2A receptors, antipsychotic effects are associated with antagonists - in fact, 5-HT2A agonists can cause hallucinations and 5-HT2B agonists cause cardiotoxicity. It is known that 5-HT2A TM6 residues W6.48, F6.51, and F6.52 impact ligand binding and function; however, ligand interactions with these residues at the 5-HT2C receptor have not been reported. To predict and validate molecular determinants for 5-HT2C-specific activation, results from receptor homology modelling, ligand docking, and molecular dynamics simulation studies were compared with experimental results for ligand binding and function at wild type and W6.48A, F6.51A, and F6.52A point-mutated 5-HT2C receptors.

Recombinant HT{sub m4} gene, protein and assays

Science.gov (United States)

Lim, B.; Adra, C.N.; Lelias, J.M.

1996-09-03

The invention relates to a recombinant DNA molecule which encodes a HT{sub m4} protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT{sub m4} protein and a recombinant HT{sub m4} protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 2 figs.

Characterized the pattern of the material deposition in the HL-2A tokamak

Energy Technology Data Exchange (ETDEWEB)

Cai, Laizhong, E-mail: cailz@swip.ac.cn [Southwestern Institute of Physics, P.O.Box 432, Chengdu, Sichuan 610041 (China); Wang, Jianbao; Wu, Ting; Zeng, Xiaoxiao [Southwestern Institute of Physics, P.O.Box 432, Chengdu, Sichuan 610041 (China); Hai, Ran; Ding, Hongbin [Dalian University of Technology, Dalian, Liaoning 116024 (China)

2017-03-15

Since the divertor geometry of a tokamak has a strong impact on the material erosion and deposition on the wall and HL-2A has a unique divertor configuration, it is necessary to investigate the material deposition pattern in HL-2A although a few results on other tokamaks have already been published. In this paper, tiles retrieved from the vessel are analyzed ex-situ by SIMS, SEM and laser-induced breakdown spectroscopy (LIBS). And deposition behind the lower divertor is in-situ measured by a quartz crystal microbalance (QMB). The deposition in HL-2A displays a complex pattern and clear localization characteristic. The thickness of the deposition layer varies in the range of 0-4μm. And in-situ diagnostic of QMB indicates that the average thickness of the deposition layer per pulse is over ten nanometers. In addition, the results imply that Si, Fe and D have different behaviors during the material deposition in HL-2A.

Confinement and diffusion in tokamaks

International Nuclear Information System (INIS)

McWilliams, R.

1988-01-01

The effect of electric field fluctuations on confinement and diffusion in tokamak is discussed. Based on the experimentally determined cross-field turbolent diffusion coefficient, D∼3.7*cT e /eB(δn i /n i ) rms which is also derived by a simple theory, the cross-field diffusion time, tp=a 2 /D, is calculated and compared to experimental results from 51 tokamak for standard Ohmic operation

Physics design of the HL-2A tokamak

International Nuclear Information System (INIS)

Gao Qingdi; Li Fangzhu; Zhang Jinhua; Pan Yudong; Jiao Yiming

2005-10-01

An overview report for the physics design of the HL-2A tokamak is presented. By numerically analyzing the plasma shaping and the vertical instability due to plasma elongation, the requirements for the currents of poloidal magnetic field coils and the control system are put forward. Controlling the plasma profile by using NBI (neutral beam injection) and LHCD (lower hybrid current drive) is investigated, and the high performance modes of operation in HL-2A and modeled and designed. The magnetohydrodynamic instabilities in improved confinement configuration (RS configuration) are studied so as to point out the way of plasma control to perform stationary high performance discharges in HL-2A. In order to offer data for updating the HL-2A divertor, performances of the divertor plasma are simulated. (authors)

A nonlinear relationship between cerebral serotonin transporter and 5-HT(2A) receptor binding: an in vivo molecular imaging study in humans

DEFF Research Database (Denmark)

Erritzoe, David; Holst, Klaus; Frokjaer, Vibe G.

2010-01-01

Serotonergic neurotransmission is involved in the regulation of physiological functions such as mood, sleep, memory, and appetite. Within the serotonin transmitter system, both the postsynaptically located serotonin 2A (5-HT2A) receptor and the presynaptic serotonin transporter (SERT) are sensitive...... tomography. Within each individual, a regional intercorrelation for the various brain regions was seen with both markers, most notably for 5-HT2A receptor binding. An inverted U-shaped relationship between the 5-HT2A receptor and the SERT binding was identified. The observed regional intercorrelation...

Status of the tokamak program

Science.gov (United States)

Sheffield, J.

1981-08-01

For a specific configuration of magnetic field and plasma to be economically attractive as a commercial source of energy, it must contain a high-pressure plasma in a stable fashion while thermally isolating the plasma from the walls of the containment vessel. The tokamak magnetic configuration is presently the most successful in terms of reaching the considered goals. Tokamaks were developed in the USSR in a program initiated in the mid-1950s. By the early 1970s tokamaks were operating not only in the USSR but also in the U.S., Australia, Europe, and Japan. The advanced state of the tokamak program is indicated by the fact that it is used as a testbed for generic fusion development - for auxiliary heating, diagnostics, materials - as well as for specific tokamak advancement. This has occurred because it is the most economic source of a large, reproducible, hot, dense plasma. The basic tokamak is considered along with tokamak improvements, impurity control, additional heating, particle and power balance in a tokamak, aspects of microscopic transport, and macroscopic stability.

5-HT1A receptors modulate small-conductance Ca2+-activated K+ channels

DEFF Research Database (Denmark)

Grunnet, Morten; Jespersen, Thomas; Perrier, Jean-François

2004-01-01

Small-conductance calcium-activated potassium channels (SK) are responsible for the medium afterhyperpolarisation (mAHP) following action potentials in neurons. Here we tested the ability of serotonin (5-HT) to modulate the activity of SK channels by coexpressing 5-HT1A receptors with different...

Molecular modeling and docking studies of human 5-hydroxytryptamine 2A (5-HT2A) receptor for the identification of hotspots for ligand binding.

Science.gov (United States)

Kanagarajadurai, Karuppiah; Malini, Manoharan; Bhattacharya, Aditi; Panicker, Mitradas M; Sowdhamini, Ramanathan

2009-12-01

The serotonergic system has been implicated in emotional and cognitive function. In particular, 5-HT(2A) (5-hydroxytrytamine receptor 2A) is attributed to a number of disorders like schizophrenia, depression, eating disorders and anxiety. 5-HT(2A), being a GPCR (G-protein coupled receptor), is important in the pharmaceutical industry as a proven target for these disorders. Despite their extensive clinical importance, the structural studies of this protein is lacking due to difficulties in determining its crystal structure. We have performed sequence analysis and molecular modeling of 5-HT(2A) that has revealed a set of conserved residues and motifs considered to play an important role in maintaining structural integrity and function of the receptor. The analysis also revealed a set of residues specific to the receptor which distinguishes them from other members of the subclass and their orthologs. Further, starting from the model structure of human 5-HT(2A) receptor, docking studies were attempted to envisage how it might interact with eight of its ligands (such as serotonin, dopamine, DOI, LSD, haloperidol, ketanserin, risperidone and clozapine). The binding studies of dopamine to 5-HT(2A) receptor can bring up better understanding in the etiology of a number of neurological disorders involving both these two receptors. Our sequence analysis and study of interactions of this receptor with other ligands reveal additional residue hotspots such as Asn 363 and Tyr 370. The function of these residues can be further analyzed by rational design of site-directed mutagenesis. Two distinct binding sites are identified which could play important roles in ligand binding and signaling.

Aphid Infestation Increases Fusarium langsethiae and T-2 and HT-2 Mycotoxins in Wheat

Science.gov (United States)

Drakulic, Jassy; Ajigboye, Olubukola; Swarup, Ranjan; Bruce, Toby

2016-01-01

ABSTRACT Fusarium langsethiae is a fungal pathogen of cereal crops that is an increasing problem in northern Europe, but much of its epidemiology is poorly understood. The species produces the mycotoxins T-2 and HT-2, which are highly toxic. It was hypothesized that grain aphids, Sitobion avenae, may transmit F. langsethiae inoculum between wheat plants, and a series of transmission experiments and volatile chemical analyses was performed to test this. Manual translocation of aphids from inoculated to uninfected hosts resulted in pathogen DNA accumulation in hosts. However, the free movement of wingless aphids from infected to healthy plants did not. The addition of winged aphids reared on F. langsethiae-inoculated wheat seedlings to wheat plants also did not achieve successful pathogen transfer. While our data suggested that aphid transmission of the pathogen was not very efficient, we observed an increase in disease when aphids were present. After seedling inoculation, an increase in pathogen DNA accumulation in seedling leaves was observed upon treatment with aphids. Furthermore, the presence of aphids on wheat plants with F. langsethiae-inoculated ears not only led to a rise in the amount of F. langsethiae DNA in infected grain but also to an increase in the concentrations of T-2 and HT-2 toxins, with more than 3-fold higher toxin levels than diseased plants without aphids. This work highlights that aphids increase the susceptibility of wheat host plants to F. langsethiae and that aphid infestation is a risk factor for accumulating increased levels of T-2 and HT-2 in wheat products. IMPORTANCE Fusarium langsethiae is shown here to cause increased contamination levels of grain with toxins produced by fungus when aphids share the host plant. This effect has also recently been demonstrated with Fusarium graminearum, yet the two fungal species show stark differences in their effect on aphid populations. In both cases, aphids improve the ability of the pathogens to

Effects of autoshaping procedures on 3H-8-OH-DPAT-labeled 5-HT1a binding and 125I-LSD-labeled 5-HT2a binding in rat brain.

Science.gov (United States)

Tomie, Arthur; Di Poce, Jason; Aguado, Allison; Janes, Amy; Benjamin, Daniel; Pohorecky, Larissa

2003-06-13

Effects of experience with Pavlovian autoshaping procedures on lever-press autoshaping conditioned response (CR) performance and 3H-8-OH-DPAT-labeled binding of 5-HT(1a) receptors as well as 125I-LSD-labeled binding of 5-HT(2a) receptors were evaluated in four groups of male Long-Evans hooded rats. Two groups of rats (Group Paired High CR and Group Paired Low CR) received Pavlovian autoshaping procedures wherein the presentation of a lever (conditioned stimulus, CS) was followed by the response-independent presentation of food (unconditioned stimulus, US). Rats in Group Paired High CR (n=12) showed more rapid CR acquisition and higher asymptotic levels of lever-press autoshaping CR performance relative to rats in Group Low CR (n=12). Group Omission (n=9) received autoshaping with an omission contingency, such that performing the lever-press autoshaping CR resulted in the cancellation the food US, while Group Random (n=9) received presentations of lever CS and food US randomly with respect to one another. Though Groups Omission and Random did not differ in lever-press autoshaping CR performance, Group Omission showed significantly lower levels of 3H-8-OH-DPAT-labeled 5-HT(1a) binding in post-synaptic areas (frontal cortex, septum, caudate putamen), as well as significantly higher plasma corticosterone levels than Group Random. In addition, Group Random showed higher levels of 3H-8-OH-DPAT-labeled 5-HT(1a) binding in pre-synaptic somatodendritic autoreceptors on dorsal raphe nucleus relative to each of the other three groups. Autoradiographic analysis of 125I-LSD-labeled 5-HT(2a) receptor binding revealed no significant differences between Groups Paired High CR and Paired Low CR or between Groups Omission and Random in any brain regions.

Experiments on cleaning effects of TDC, GDC and ECR-DC in the JFT-2M tokamak

International Nuclear Information System (INIS)

Matsuzaki, Y.; Ogawa, H.; Miura, Y.; Ohtsuka, H.; Suzuki, N.; Yamauchi, T.; Tani, T.; Mori, M.

1987-01-01

The cleaning effects of Taylor-type discharge cleaning (TDC), glow discharge cleaning (GDC) and ECR discharge cleaning (ECR-DC) were studied in the JFT-2M tokamak by comparing the properties of resulting tokamak plasmas, by observing the surface composition of samples and by residual gas analysis. The operational parameters of the three discharge cleaning techniques were as follows; the plasma current for TDC is 20 kA, the DC current for GDC is 3 A and the RF power for ECR-DC is 2.3 kW. Parameters of the tokamak plasmas such as loop voltages, radiation losses, spectra emission of oxygen, maximum mean electron densities and profiles of electron temperature were improved as the TDC and ECR-DC proceeded. Changes in the surface composition of samples were measured by Auger electron spectrosopy. The results showed that during the TDC and ECR-DC oxygen was reduced, while GDC reduced mainly carbon. Residual gas analysis performed during discharge cleaning corroborated these results. (orig.)

Present status of Tokamak research

International Nuclear Information System (INIS)

Basu, Jayanta

1991-01-01

The scenario of thermonuclear fusion research is presented, and the tokamak which is the most promising candidate as a fusion reactor is introduced. A brief survey is given of the most noteworthy tokamaks in the global context, and fusion programmes relating to Next Step devices are outlined. Supplementary heating of tokamak plasma by different methods is briefly reviewed; the latest achievements in heating to fusion temperatures are also reported. The progress towards the high value of the fusion product necessary for ignition is described. The improvement in plasma confinement brought about especially by the H-mode, is discussed. The latest situation in pushing up Β for increasing the efficiency of a tokamak is elucidated. Mention is made of the different types of wall treatment of the tokamak vessel for impurity control, which has led to a significant improvement in tokamak performance. Different methods of current drive for steady state tokamak operation are reviewed, and the issue of current drive efficiency is addressed. A short resume is given of the various diagnostic methods which are employed on a routine basis in the major tokamak centres. A few diagnostics recently developed or proposed in the context of the advanced tokamaks as well as the Next Step devices are indicated. The important role of the interplay between theory, experiment and simulation is noted, and the areas of investigation requiring concerted effort for further progress in tokamak research are identified. (author). 17 refs

Differences in 5-HT2A and mGlu2 Receptor Expression Levels and Repressive Epigenetic Modifications at the 5-HT2A Promoter Region in the Roman Low- (RLA-I) and High- (RHA-I) Avoidance Rat Strains

DEFF Research Database (Denmark)

Fomsgaard, Luna; Moreno, Jose L; de la Fuente Revenga, Mario

2018-01-01

The serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptors regulate each other and are associated with schizophrenia. The Roman high- (RHA-I) and the Roman low- (RLA-I) avoidance rat strains present well-differentiated behavioral profiles, with the RHA-I strain emerging as a putativ...

5-HT2a receptor in mPFC influences context-guided reconsolidation of object memory in perirhinal cortex

Science.gov (United States)

Morici, Juan Facundo; Miranda, Magdalena; Gallo, Francisco Tomás; Zanoni, Belén; Bekinschtein, Pedro

2018-01-01

Context-dependent memories may guide adaptive behavior relaying in previous experience while updating stored information through reconsolidation. Retrieval can be triggered by partial and shared cues. When the cue is presented, the most relevant memory should be updated. In a contextual version of the object recognition task, we examined the effect of medial PFC (mPFC) serotonin 2a receptor (5-HT2aR) blockade during retrieval in reconsolidation of competing objects memories. We found that mPFC 5-HT2aR controls retrieval and reconsolidation of object memories in the perirhinal cortex (PRH), but not in the dorsal hippocampus in rats. Also, reconsolidation of objects memories in PRH required a functional interaction between the ventral hippocampus and the mPFC. Our results indicate that in the presence of conflicting information at retrieval, mPFC 5-HT2aR may facilitate top-down context-guided control over PRH to control the behavioral response and object memory reconsolidation. PMID:29717980

2D full-wave simulation of waves in space and tokamak plasmas

Directory of Open Access Journals (Sweden)

Kim Eun-Hwa

2017-01-01

Full Text Available Simulation results using a 2D full-wave code (FW2D for space and NSTX fusion plasmas are presented. The FW2D code solves the cold plasma wave equations using the finite element method. The wave code has been successfully applied to describe low frequency waves in planetary magnetospheres (i.e., dipole geometry and the results include generation and propagation of externally driven ultra-low frequency waves via mode conversion at Mercury and mode coupling, refraction and reflection of internally driven field-aligned propagating left-handed electromagnetic ion cyclotron (EMIC waves at Earth. In this paper, global structure of linearly polarized EMIC waves is examined and the result shows such resonant wave modes can be localized near the equatorial plane. We also adopt the FW2D code to tokamak geometry and examine radio frequency (RF waves in the scape-off layer (SOL of tokamaks. By adopting the rectangular and limiter boundary, we compare the results with existing AORSA simulations. The FW2D code results for the high harmonic fast wave heating case on NSTX with a rectangular vessel boundary shows excellent agreement with the AORSA code.

2D full-wave simulation of waves in space and tokamak plasmas

Science.gov (United States)

Kim, Eun-Hwa; Bertelli, Nicola; Johnson, Jay; Valeo, Ernest; Hosea, Joel

2017-10-01

Simulation results using a 2D full-wave code (FW2D) for space and NSTX fusion plasmas are presented. The FW2D code solves the cold plasma wave equations using the finite element method. The wave code has been successfully applied to describe low frequency waves in planetary magnetospheres (i.e., dipole geometry) and the results include generation and propagation of externally driven ultra-low frequency waves via mode conversion at Mercury and mode coupling, refraction and reflection of internally driven field-aligned propagating left-handed electromagnetic ion cyclotron (EMIC) waves at Earth. In this paper, global structure of linearly polarized EMIC waves is examined and the result shows such resonant wave modes can be localized near the equatorial plane. We also adopt the FW2D code to tokamak geometry and examine radio frequency (RF) waves in the scape-off layer (SOL) of tokamaks. By adopting the rectangular and limiter boundary, we compare the results with existing AORSA simulations. The FW2D code results for the high harmonic fast wave heating case on NSTX with a rectangular vessel boundary shows excellent agreement with the AORSA code.

Real time equilibrium reconstruction algorithm in EAST tokamak

International Nuclear Information System (INIS)

Wang Huazhong; Luo Jiarong; Huang Qinchao

2004-01-01

The EAST (HT-7U) superconducting tokamak is a national project of China on fusion research, with a capability of long-pulse (∼1000 s) operation. In order to realize a long-duration steady-state operation of EAST, some significant capability of real-time control is required. It would be very crucial to obtain the current profile parameters and the plasma shapes in real time by a flexible control system. As those discharge parameters cannot be directly measured, so a current profile consistent with the magnetohydrodynamic equilibrium should be evaluated from external magnetic measurements, based on a linearized iterative least square method, which can meet the requirements of the measurements. The arithmetic that the EFIT (equilibrium fitting code) is used for reference will be given in this paper and the computational efforts are reduced by parameterizing the current profile linearly in terms of a number of physical parameters. In order to introduce this reconstruction algorithm clearly, the main hardware design will be listed also. (authors)

Tokamak engineering mechanics

CERN Document Server

Song, Yuntao; Du, Shijun

2013-01-01

Tokamak Engineering Mechanics offers concise and thorough coverage of engineering mechanics theory and application for tokamaks, and the material is reinforced by numerous examples. Chapter topics include general principles, static mechanics, dynamic mechanics, thermal fluid mechanics and multiphysics structural mechanics of tokamak structure analysis. The theoretical principle of the design and the methods of the analysis for various components and load conditions are presented, while the latest engineering technologies are also introduced. The book will provide readers involved in the study

Neutronic analysis of fusion tokamak devices by PHITS

International Nuclear Information System (INIS)

Sukegawa, Atsuhiko M.; Takiyoshi, Kouji; Amano, Toshio; Kawasaki, Hiromitsu; Okuno, Koichi

2011-01-01

A complete 3D neutronic analysis by PHITS (Particle and Heavy Ion Transport code System) has been performed for fusion tokamak devices such as JT-60U device and JT-60 Superconducting tokamak device (JT-60 Super Advanced). The mono-energetic neutrons (E n =2.45 MeV) of the DD fusion devices are used for the neutron source in the analysis. The visual neutron flux distribution for the estimation of the port streaming and the dose rate around the fusion tokamak devices has been calculated by the PHITS. The PHITS analysis makes it clear that the effect of the port streaming of superconducting fusion tokamak device with the cryostat is crucial and the calculated neutron spectrum results by PHITS agree with the MCNP-4C2 results. (author)

The tokamak as a neutron source

International Nuclear Information System (INIS)

Hendel, H.W.; Jassby, D.L.

1989-11-01

This paper describes the tokamak in its role as a neutron source, with emphasis on experimental results for D-D neutron production. The sections summarize tokamak operation, sources of fusion and non-fusion neutrons, principal neutron detection methods and their calibration, neutron energy spectra and fluxes outside the tokamak plasma chamber, history of neutron production in tokamaks, neutron emission and fusion power gain from JET and TFTR (the largest present-day tokamaks), and D-T neutron production from burnup of D-D tritons. This paper also discusses the prospects for future tokamak neutron production and potential applications of tokamak neutron sources. 100 refs., 16 figs., 4 tabs

MDMA self-administration fails to alter the behavioral response to 5-HT(1A) and 5-HT(1B) agonists.

Science.gov (United States)

Aronsen, Dane; Schenk, Susan

2016-04-01

Regular use of the street drug, ecstasy, produces a number of cognitive and behavioral deficits. One possible mechanism for these deficits is functional changes in serotonin (5-HT) receptors as a consequence of prolonged 3,4 methylenedioxymethamphetamine (MDMA)-produced 5-HT release. Of particular interest are the 5-HT(1A) and 5-HT(1B) receptor subtypes since they have been implicated in several of the behaviors that have been shown to be impacted in ecstasy users and in animals exposed to MDMA. This study aimed to determine the effect of extensive MDMA self-administration on behavioral responses to the 5-HT(1A) agonist, 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT), and the 5-HT(1B/1A) agonist, RU 24969. Male Sprague-Dawley rats self-administered a total of 350 mg/kg MDMA, or vehicle, over 20-58 daily self-administration sessions. Two days after the last self-administration session, the hyperactive response to 8-OH-DPAT (0.03-1.0 mg/kg) or the adipsic response to RU 24969 (0.3-3.0 mg/kg) were assessed. 8-OH-DPAT dose dependently increased horizontal activity, but this response was not altered by MDMA self-administration. The dose-response curve for RU 24969-produced adipsia was also not altered by MDMA self-administration. Cognitive and behavioral deficits produced by repeated exposure to MDMA self-administration are not likely due to alterations in 5-HT(1A) or 5-HT(1B) receptor mechanisms.

Converging evidence for central 5-HT effects in acute tryptophan depletion

DEFF Research Database (Denmark)

Crockett, Molly; Clark, Luke; Roiser, Jonathan

2012-01-01

the validity of ATD.2 Although we agree that ATD's effects on 5-HT activity at the molecular level need further clarification, van Donkelaar et al.2 goes too far in challenging whether ATD exerts its effects through serotonergic mechanisms. There is strong evidence that ATD reduces brain 5-HT and disrupts......Acute tryptophan depletion (ATD), a dietary technique for manipulating brain serotonin (5-HT) function, has advanced our understanding of 5-HT mechanisms in the etiology and treatment of depression and other affective disorders.1 A recent review article in Molecular Psychiatry questioned...

Neutral beam in ALVAND IIC tokamak

International Nuclear Information System (INIS)

Ghrannevisse, M.; Moradshahi, M.; Avakian, M.

1992-01-01

Neutral beams have a wide application in tokamak experiments. It used to heat; fuel; adjust electric potentials in plasmas and diagnose particles densities and momentum distributions. It may be used to sustain currents in tokamaks to extend the pulse length. A 5 KV; 500 mA ion source has been constructed by plasma physics group, AEOI and it used to produce plasma and study the plasma parameters. Recently this ion source has been neutralized and it adapted to a neutral beam source; and it used to heat a cylindrical DC plasma and the plasma of ALVAND IIC Tokamak which is a small research tokamak with a minor radius of 12.6 cm, and a major radius of 45.5 cm. In this paper we report the neutralization of the ion beam and the results obtained by injection of this neutral beam into plasmas. (author) 2 refs., 4 figs

HT oxidation activity of soil irradiated with gamma radiation

International Nuclear Information System (INIS)

Momoshima, Noriyuki; Tjahaja, P.I.; Takashima, Yoshimasa

1992-01-01

The HT oxidation activity was examined for soils irradiated with 60 Co γ-rays at various doses. The HT oxidation rate decreased with increase of initial H 2 concentration, indicating a similar oxidation mechanism between HT and H 2 . Irradiated soils showed decrease of oxidation activity with dose suggests that HT and H 2 oxidation activities were affected by sterilization with γ-rays. The decline of the oxidation activity with dose was analyzed by a composite of two components with different radiosensitivity and they were considered to be activities of soil microorganisms and abiotic soil enzymes. The oxidation activity due to soil microorganisms would be important at low dose range and more radioresistant abiotic soil enzymes would be responsible for the oxidation activity observed at more than several kGy. In non-irradiated soil about half of the oxidation activity was considered resulting from abiotic soil enzymes. (author)

Status of tokamak research

International Nuclear Information System (INIS)

Rawls, J.M.

1979-10-01

An overall review of the tokamak program is given with particular emphasis upon developments over the past five years in the theoretical and experimental elements of the program. A summary of the key operating parameters for the principal tokamaks throughout the world is given. Also discussed are key issues in plasma confinement, plasma heating, and tokamak design

Estimation of Zeff in Novillo Tokamak

International Nuclear Information System (INIS)

Valencia, R.; Olayo, G.; Cruz, G.; Lopez, R.; Chavez, E.; Melendez, L.; Flores, A.; Gaytan, E.

1996-01-01

We estimated the Z eff in the Novillo Tokamak after having applied a HeGDC process through two different methods: anomaly factor and mass spectrometry. The first one gave a Z eff value of 2.07 for a tokamak discharge of 4350 A plasma current and 3 V of loop voltage. By mass spectrometry 30 s after the discharge had finished a Z eff of 4.19 was obtained for the same discharge. By mass spectrometry we observed that the Z eff value is a time function. Furthermore this method is helpful for evaluating the level of impurities after many discharges in Novillo Tokamak. (orig.)

Radiosynthesis and in vivo evaluation of a series of substituted {sup 11}C-phenethylamines as 5-HT{sub 2A} agonist PET tracers

Energy Technology Data Exchange (ETDEWEB)

Ettrup, Anders; Santini, Martin A.; Palner, Mikael; Knudsen, Gitte M. [Copenhagen University Hospital, Neurobiology Research Unit, Copenhagen (Denmark); Copenhagen University Hospital, Rigshospitalet, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen (Denmark); Hansen, Martin; Paine, James; Kristensen, Jesper; Begtrup, Mikael [University of Copenhagen, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Copenhagen (Denmark); Copenhagen University Hospital, Rigshospitalet, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen (Denmark); Gillings, Nic; Herth, Matthias M.; Madsen, Jacob [Copenhagen University Hospital, Rigshospitalet, PET and Cyclotron Unit, Copenhagen (Denmark); Copenhagen University Hospital, Rigshospitalet, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen (Denmark); Lehel, Szabolcs [Copenhagen University Hospital, Rigshospitalet, PET and Cyclotron Unit, Copenhagen (Denmark)

2011-04-15

Positron emission tomography (PET) imaging of serotonin 2A (5-HT{sub 2A}) receptors with agonist tracers holds promise for the selective labelling of 5-HT{sub 2A} receptors in their high-affinity state. We have previously validated [{sup 11}C]Cimbi-5 and found that it is a 5-HT{sub 2A} receptor agonist PET tracer. In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [{sup 11}C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT{sub 2A} receptor agonist PET tracers in the pig brain. Each radiotracer was injected intravenously into anaesthetized Danish Landrace pigs, and the pigs were subsequently scanned for 90 min in a high-resolution research tomography scanner. To evaluate 5-HT{sub 2A} receptor binding, cortical nondisplaceable binding potentials (BP{sub ND}) were calculated using the simplified reference tissue model with the cerebellum as a reference region. After intravenous injection, all compounds entered the brain and distributed preferentially into the cortical areas, in accordance with the known 5-HT{sub 2A} receptor distribution. The largest target-to-background binding ratio was found for [{sup 11}C]Cimbi-36 which also had a high brain uptake compared to its analogues. The cortical binding of [{sup 11}C]Cimbi-36 was decreased by pretreatment with ketanserin, supporting 5-HT{sub 2A} receptor selectivity in vivo. [{sup 11}C]Cimbi-82 and [{sup 11}C]Cimbi-21 showed lower cortical BP{sub ND}, while [{sup 11}C]Cimbi-27, [{sup 11}C]Cimbi-29, [{sup 11}C]Cimbi-31 and [{sup 11}C]Cimbi-88 gave rise to cortical BP{sub ND} similar to that of [{sup 11}C]Cimbi-5. [{sup 11}C]Cimbi-36 is currently the most promising candidate for investigation of 5-HT{sub 2A} receptor agonist binding in the living human brain with PET. (orig.)

Tokamak ARC damage

International Nuclear Information System (INIS)

Murray, J.G.; Gorker, G.E.

1985-01-01

Tokamak fusion reactors will have large plasma currents of approximately 10 MA with hundreds of megajoules stored in the magnetic fields. When a major plasma instability occurs, the disruption of the plasma current induces voltage in the adjacent conducting structures, giving rise to large transient currents. The induced voltages may be sufficiently high to cause arcing across sector gaps or from one protruding component to another. This report reviews a tokamak arcing scenario and provides guidelines for designing tokamaks to minimize the possibility of arc damage

Tokamak ARC damage

Energy Technology Data Exchange (ETDEWEB)

Murray, J.G.; Gorker, G.E.

1985-01-01

Tokamak fusion reactors will have large plasma currents of approximately 10 MA with hundreds of megajoules stored in the magnetic fields. When a major plasma instability occurs, the disruption of the plasma current induces voltage in the adjacent conducting structures, giving rise to large transient currents. The induced voltages may be sufficiently high to cause arcing across sector gaps or from one protruding component to another. This report reviews a tokamak arcing scenario and provides guidelines for designing tokamaks to minimize the possibility of arc damage.

Simulation of a major tokamak disruption

International Nuclear Information System (INIS)

White, R.B.; Monticello, D.A.; Rosenbluth, M.N.

1977-08-01

It is known that the internal tokamak disruption leads to a current profile which is flattened inside the surface where the safety factor equals unity. It is shown that such a profile can lead to m = 2 magnetic islands which grow to fill a substantial part of the tokamak cross section in a time consistent with the observations of the major disruption

G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations

DEFF Research Database (Denmark)

Ísberg, Vignir; Balle, Thomas; Sander, Tommy

2011-01-01

molecular dynamics (MD) simulations. The driving force for the transformation was the addition of several known intermolecular and receptor interhelical hydrogen bonds enforcing the necessary helical and rotameric movements. Subsquent MD simulations without constraints confirmed the stability......A 5-HT(2A) receptor model was constructed by homology modeling based on the ß(2)-adrenergic receptor and the G protein-bound opsin crystal structures. The 5-HT(2A) receptor model was transferred into an active conformation by an agonist ligand and a G(aq) peptide in four subsequent steered...

A study on the fusion reactor - Development of MHD stability and transport code for KT-2 tokamak

Energy Technology Data Exchange (ETDEWEB)

Lee, Jae Koo; Shin, Kyo Jin [Pohang University of Science and Tecnology, Pohang (Korea, Republic of)

1996-08-01

MHD Stability analyses for KT-2 Tokamak were carried out by using CART (Resistive 3-D) Code. Linear Growth rates and linear perturbed eigen function of both N=0 axisymmetric mode and N=1 kink modes of highly elongated tokamak plasmas, in the presence of a conducting wall at various distances are computed and linear and nonlinear evolution of N=0 axisymmetric modes are simulated. 26 refs., 25 figs. (author)

Psychopharmacology of 5-HT1A receptors

International Nuclear Information System (INIS)

Cowen, Philip J.

2000-01-01

Serotonin 1A (5-HT 1A ) receptors are located on both 5-HT cell bodies where they act as inhibitory autoreceptors and at postsynaptic sites where they mediate the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT 1A receptors in humans can be measured using the technique of pharmacological challenge. For example, acute administration of a selective 5-HT 1A receptor agonist, such as ipsapirone, decreases body temperature and increases plasma cortisol through activation of pre- and postsynaptic 5-HT 1A receptors, respectively. Use of this technique has demonstrated that unmedicated patients with major depression have decreased sensitivity of both pre- and postsynaptic 5-HT 1A receptors. Treatment with selective serotonin reuptake inhibitors further down-regulates 5-HT 1A receptor activity. Due to the hypotheses linking decreased sensitivity of 5-HT 1A autoreceptors with the onset of antidepressant activity, there is current interest in the therapeutic efficacy of combined treatment with selective serotonin reuptake inhibitors and 5-HT 1A receptor antagonists

Novel aza-analogous ergoline derived scaffolds as potent serotonin 5-HT6 and dopamine D2 receptor ligands

DEFF Research Database (Denmark)

Krogsgaard-Larsen, Niels; Jensen, Anders A.; Schrøder, T.J.

2014-01-01

By introducing distal substituents on a tetracyclic scaffold resembling the ergoline structure, two series of analogues were achieved exhibiting subnanomolar receptor binding affinities for the dopamine D2 and serotonin 5-HT6 receptor subtype, respectively. While the 5-HT6 ligands were antagonists......, the D2 ligands displayed intrinsic activities ranging from full agonism to partial agonism with low intrinsic activity. These structures could potentially be interesting for treatment of neurological diseases such as schizophrenia, Parkinson’s disease, and cognitive deficits....

Environmental HTO/HT sampler development

International Nuclear Information System (INIS)

Workman, W.J.G.; Brown, R.M.; Wood, M.J.

1992-12-01

Tests of retention by several drying agents of HTO from an air stream containing HT have been performed. Two batches of Molecular Sieve (MS) 4A retained up to 1.3% of HT passed through them in contrast to material tested in 1986, when retention was -4 . Retention of 10 -5 to 10 -6 was observed for DRIERITE (anhydrous calcium sulphate) and Silica Gel. DRIERITE is preferred over Silica Gel as a desiccant in an air sampler for environmental HTO/HT, because it is much easier to decontaminate for reuse. An improved air sampler has been designed, 2 units constructed and components procured for 3 more. The air sampler may be line or battery operated, accommodates up to four 120 g drier or oxidizer traps, and will pump up to 4 L/min for up to 24 hours on battery power. It is build into a rugged aluminum case and weighs approximately 11 kg overall, facilitating deployment in the field

What would 5-HT do? Regional diversity of 5-HT1 receptor modulation of primary afferent neurotransmission

OpenAIRE

Connor, Mark

2012-01-01

5-HT (serotonin) is a significant modulator of sensory input to the CNS, but the only analgesics that selectively target G-protein-coupled 5-HT receptors are highly specific for treatment of headache. Two recent papers in BJP shed light on this puzzling situation by showing that primary afferent neurotransmission to the superficial layers of the spinal and trigeminal dorsal is inhibited by different subtypes of the 5-HT1 receptor – 5-HT1B(and 1D) in the trigeminal dorsal horn and 5-HT1A in th...

Tokamak reactor studies

International Nuclear Information System (INIS)

Baker, C.C.

1981-01-01

This paper presents an overview of tokamak reactor studies with particular attention to commercial reactor concepts developed within the last three years. Emphasis is placed on DT fueled reactors for electricity production. A brief history of tokamak reactor studies is presented. The STARFIRE, NUWMAK, and HFCTR studies are highlighted. Recent developments that have increased the commercial attractiveness of tokamak reactor designs are discussed. These developments include smaller plant sizes, higher first wall loadings, improved maintenance concepts, steady-state operation, non-divertor particle control, and improved reactor safety features

Disassembly of JT-60 tokamak device and ancillary facilities for JT-60 tokamak

International Nuclear Information System (INIS)

Okano, Fuminori; Ichige, Hisashi; Miyo, Yasuhiko; Kaminaga, Atsushi; Sasajima, Tadayuki; Nishiyama, Tomokazu; Yagyu, Jun-ichi; Ishige, Youichi; Suzuki, Hiroaki; Komuro, Kenichi; Sakasai, Akira; Ikeda, Yoshitaka

2014-03-01

The disassembly of JT-60 tokamak device and its peripheral equipments, where the total weight was about 5400 tons, started in 2009 and accomplished in October 2012. This disassembly was required process for JT-60SA project, which is the Satellite Tokamak project under Japan-EU international corroboration to modify the JT-60 to the superconducting tokamak. This work was the first experience of disassembling a large radioactive fusion device based on Radiation Hazard Prevention Act in Japan. The cutting was one of the main problems in this disassembly, such as to cut the welded parts together with toroidal field coils, and to cut the vacuum vessel into two. After solving these problems, the disassembly completed without disaster and accident. This report presents the outline of the JT-60 disassembly, especially tokamak device and ancillary facilities for tokamak device. (author)

5HT(1A) and 5HT(1B) receptors of medial prefrontal cortex modulate anxiogenic-like behaviors in rats.

Science.gov (United States)

Solati, Jalal; Salari, Ali-Akbar; Bakhtiari, Amir

2011-10-31

Medial prefrontal cortex (MPFC) is one of the brain regions which play an important role in emotional behaviors. The purpose of the present study was to evaluate the role of 5HT(1A) and 5HT(1B) receptors of the MPFC in modulation of anxiety behaviors in rats. The elevated plus maze (EPM) which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used. Bilateral intra-MPFC administration of 5HT(1A) receptor agonist, 8-OH-DPAT (5, 10, and 50 ng/rat) decreased the percentages of open arm time (OAT%) and open arm entries (OAE%), indicating an anxiogenic response. Moreover, administration of 5HT(1A) receptor antagonist, NAN-190 (0.25, 0.5, and 1 μg/rat) significantly increased OAT% and OAE%. Pre-treatment administration of NAN-190 (0.5 μg/rat), which was injected into the MPFC, reversed the anxiogenic effects of 8-OH-DPAT (5, 10, and 50 ng/rat). Intra-MPFC microinjection of 5HT(1B) receptor agonist, CGS-12066A (0.25, 0.5, and 1 μg/rat) significantly decreased OAT% and OAE%, without any change in locomotor activity, indicating an anxiogenic effect. However, injection of 5HT(1B) receptor antagonist, SB-224289 (0.5, 1, and 2 μg/rat) into the MPFC showed no significant effect. In conclusion, these findings suggest that 5HT(1A) and 5HT(1B) receptors of the MPFC region modulate anxiogenic-like behaviors in rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Radial electric field at the plasma edge on the FT-2 Tokamak in regimes with large gradients

International Nuclear Information System (INIS)

Lashkul, S.; Popov, A.

2001-01-01

The transport barrier formation is widely believed to be the fundamental element of transition into improved confinement regimes (H-mode). Experiments on many tokamaks demonstrate that transport barrier formation is connected with the suppression of turbulent transport by shear of E x B drift. Therefore, the calculation of radial electric field is of great importance. Our work is devoted to progress the neoclassical theory by taking into account electron viscosity and non-linear effects (ion inertia), presented results being valuable for interpretation transition into H-mode at the plasma edge in small tokamaks. Calculations of the electric field profile for FT-2 tokamak (a=8cm, R 0 =55cm, Ioffe Institute, Russia) according found expressions are in the good agreement with experimental results obtained. (orig.)

Test-retest variability of high resolution positron emission tomography (PET) imaging of cortical serotonin (5HT2A) receptors in older, healthy adults

International Nuclear Information System (INIS)

Chow, Tiffany W; Mamo, David C; Uchida, Hiroyuki; Graff-Guerrero, Ariel; Houle, Sylvain; Smith, Gwenn S; Pollock, Bruce G; Mulsant, Benoit H

2009-01-01

Position emission tomography (PET) imaging using [ 18 F]-setoperone to quantify cortical 5-HT 2A receptors has the potential to inform pharmacological treatments for geriatric depression and dementia. Prior reports indicate a significant normal aging effect on serotonin 5HT 2A receptor (5HT 2A R) binding potential. The purpose of this study was to assess the test-retest variability of [ 18 F]-setoperone PET with a high resolution scanner (HRRT) for measuring 5HT 2A R availability in subjects greater than 60 years old. Methods: Six healthy subjects (age range = 65–78 years) completed two [ 18 F]-setoperone PET scans on two separate occasions 5–16 weeks apart. The average difference in the binding potential (BP ND ) as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions. We conclude that the test-retest variability of [ 18 F]-setoperone PET in elderly subjects is comparable to that of [ 18 F]-setoperone and other 5HT 2A R radiotracers in younger subject samples

Preclinical evaluation of [{sup 18}F]2FNQ1P as the first fluorinated serotonin 5-HT{sub 6} radioligand for PET imaging

Energy Technology Data Exchange (ETDEWEB)

Becker, Guillaume [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); Colomb, Julie [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); Sgambato-Faure, Veronique; Tremblay, Leon [Universite Claude Bernard Lyon 1, CNRS, Cognitive Neuroscience Center, Bron (France); Billard, Thierry [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France); Zimmer, Luc [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France)

2014-10-21

Brain serotonin 6 receptor (5-HT{sub 6}) is one of the most recently identified serotonin receptors. It is a potent therapeutic target for psychiatric and neurological diseases, e.g. schizophrenia and Alzheimer's disease. Since no specific fluorinated radioligand has yet been successfully used to study this receptor by positron emission tomography (PET) neuroimaging, the objective of the present study was to study the first 5-HT{sub 6} {sup 18}F-labelled radiotracer. 2FNQ1P, inspired by the quinolone core of a previous radiotracer candidate, GSK215083, was selected according its 5-HT{sub 6} affinity and selectivity and was radiolabelled by {sup 18}F nucleophilic substitution. The cerebral distribution of [{sup 18}F]2FNQ1P was studied in vivo in rats, cats and macaque monkeys. The chemical and radiochemical purities of [{sup 18}F]2FNQ1P were >98 %. In rats, in vitro competition with the 5-HT{sub 6} antagonist, SB258585, revealed that the radioligand was displaced dose dependently. Rat microPET studies showed low brain uptake of [{sup 18}F]2FNQ1P, reversed by the P-glycoprotein inhibitor, cyclosporin. On the contrary, PET scans in cats showed good brain penetration and specific striatal binding blocked after pretreatment with unlabelled 2FNQ1P. PET scans in macaque monkeys confirmed high specific binding in both cortical and subcortical regions, specifically decreased by pretreatment with the 5-HT{sub 6} receptor antagonist, SB258585. 2FNQ1P was initially selected because of its suitable characteristics for 5-HT{sub 6} receptor probing in vitro in terms of affinity and specificity. Although in vivo imaging in rats cannot be considered as predictive of the clinical characteristics of the radiotracer, [{sup 18}F]2FNQ1P appeared to be a suitable 5-HT{sub 6} PET tracer in feline and primate models. These preclinical results encourage us to pursue the clinical development of this first fluorinated 5-HT{sub 6} PET radiotracer. (orig.)

In search of zonal flows using cross-bispectrum analysis in the boundary plasma of the Hefei Tokamak-7

International Nuclear Information System (INIS)

Xu, G.S.; Wan, B.N.; Song, M.

2002-01-01

Langmuir probes have been used to measure the electrostatic Reynolds stress and the floating potential fluctuation in the boundary plasma of the Hefei Tokamak-7 (HT-7) [J. Li, B. N. Wan, and J. S. Mao, Plasma Phys. Controlled Fusion 42, 135 (2000)]. The cross bispectrum of r V(tilde sign) θ φ(tilde sign) f > indicates the existence of difference-frequency nonlinear phase coupling and the generation of fluctuations near the geodesic acoustic mode frequency. The inverse cascade process might be linked to the generation of zonal flows by small-scale electrostatic drift-wave turbulence

Tokamak confinement scaling laws

International Nuclear Information System (INIS)

Connor, J.

1998-01-01

The scaling of energy confinement with engineering parameters, such as plasma current and major radius, is important for establishing the size of an ignited fusion device. Tokamaks exhibit a variety of modes of operation with different confinement properties. At present there is no adequate first principles theory to predict tokamak energy confinement and the empirical scaling method is the preferred approach to designing next step tokamaks. This paper reviews a number of robust theoretical concepts, such as dimensional analysis and stability boundaries, which provide a framework for characterising and understanding tokamak confinement and, therefore, generate more confidence in using empirical laws for extrapolation to future devices. (author)

Module of lithium divertor for KTM tokamak

Energy Technology Data Exchange (ETDEWEB)

Lyublinski, I., E-mail: yublinski@yandex.ru [FSUE ' Red Star' , Moscow (Russian Federation); Vertkov, A.; Evtikhin, V.; Balakirev, V.; Ionov, D.; Zharkov, M. [FSUE ' Red Star' , Moscow (Russian Federation); Tazhibayeva, I. [IAE NNC RK, Kurchatov (Kazakhstan); Mirnov, S. [TRINITI, Troitsk, Moscow Region (Russian Federation); Khomiakov, S.; Mitin, D. [OJSC Dollezhal Institute, Moscow (Russian Federation); Mazzitelli, G. [ENEA RC Frascati (Italy); Agostini, P. [ENEA RC Brasimone (Italy)

2012-10-15

Highlights: Black-Right-Pointing-Pointer Problems of PFE degradation, tritium accumulation and plasma pollution can be overcome by the use of liquid lithium-metal with low Z. Black-Right-Pointing-Pointer Capillary-porous system (CPS) - new material in which liquid lithium fill a solid matrix from porous material. Black-Right-Pointing-Pointer Lithium divertor module for KTM tokamak is under development. Black-Right-Pointing-Pointer Lithium filled tungsten felt is offered as the base plasma facing material of divertor. Black-Right-Pointing-Pointer Results of this project addresses to the progress in the field of fusion neutrons source and fusion energy source creation. - Abstract: Activity on projects of ITER and DEMO reactors has shown that solution of problems of divertor target plates and other plasma facing elements (PFEs) based on the solid plasma facing materials cause serious difficulties. Problems of PFE degradation, tritium accumulation and plasma pollution can be overcome by the use of liquid lithium-metal with low Z. Application of lithium will allow to create a self-renewal and MHD stable liquid metal surface of the in-vessel devices possessing practically unlimited service life; to reduce power flux due to intensive re-irradiation on lithium atoms in plasma periphery that will essentially facilitate a problem of heat removal from PFE; to reduce Z{sub eff} of plasma to minimally possible level close to 1; to exclude tritium accumulation, that is provided with absence of dust products and an opportunity of the active control of the tritium contents in liquid lithium. Realization of these advantages is based on use of so-called lithium capillary-porous system (CPS) - new material in which liquid lithium fill a solid matrix from porous material. The progress in development of lithium technology and also activity in lithium experiments in the tokamaks TFTR, T-11M, T-10, FTU, NSTX, HT-7 and stellarator TJ II permits of solving the problems in development of

Magnetic field structure of experimental high beta tokamak equilibria

International Nuclear Information System (INIS)

Deniz, A.V.

1986-01-01

The magnetic field structure of several low and high β tokamaks in the Columbia High Beta Tokamak (HBT) was determined by high-impedance internal magnetic probes. From the measurement of the magnetic field, the poloidal flux, toroidal flux, toroidal current, and safety factor are calculated. In addition, the plasma position and cross-sectional shape are determined. The extent of the perturbation of the plasma by the probe was investigated and was found to be acceptably small. The tokamaks have major radii of approx.0.24 m, minor radii of approx.0.05 m, toroidal plasma current densities of approx.10 6 A/m 2 , and line-integrated electron densities of approx.10 20 m -2 . The major difference between the low and high β tokamaks is that the high β tokamak was observed to have an outward shift in major radius of both the magnetic center and peak of the toroidal current density. The magnetic center moves inward in major radius after 20 to 30 μsec, presumably because the plasma maintains major radial equilibrium as its pressure decreases from radiation due to impurity atoms. Both the equilibrium and the production of these tokamaks from a toroidal field stabilized z-pinch are modeled computationally. One tokamak evolves from a state with low β features, through a possibly unstable state, to a state with high β features

Cerebral 5-HT2A receptor binding is increased in patients with Tourette's syndrome

DEFF Research Database (Denmark)

Haugbøl, Steven; Pinborg, Lars H.; Regeur, Lisbeth

2007-01-01

Experimental and clinical data have suggested that abnormalities in the serotonergic neurotransmissions in frontal-subcortical circuits are involved in Tourette's syndrome. To test the hypothesis that the brain's 5-HT2A receptor binding is increased in patients with Tourette's syndrome, PET imagi...

Peripheral and spinal 5-HT receptors participate in the pronociceptive and antinociceptive effects of fluoxetine in rats.

Science.gov (United States)

Cervantes-Durán, C; Rocha-González, H I; Granados-Soto, V

2013-11-12

The role of 5-HT receptors in fluoxetine-induced nociception and antinociception in rats was assessed. Formalin produced a typical pattern of flinching and licking/lifting behaviors. Local peripheral ipsilateral, but not contralateral, pre-treatment with fluoxetine (0.3-3 nmol/paw) increased in a dose-dependent fashion 0.5% formalin-induced nociception. In contrast, intrathecal pretreatment with fluoxetine (0.3-3 nmol/rat) prevented nociception induced by formalin. The peripheral pronociceptive effect of fluoxetine was prevented by the 5-HT2A (ketanserin, 3-10 pmol/paw), 5-HT2B (3-(2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl)-2,4(1H,3H)-quinazolinedione(+) tartrate, RS-127445, 3-10 pmol/paw), 5-HT2C (8-[5-(2,4-dimethoxy-5-(4-trifluoromethylphenylsulphonamido) phenyl-5-oxopentyl]1,3,8-triazaspiro[4.5] decane-2,4-dione hydrochloride, RS-102221, 3-10 pmol/paw), 5-HT3 (ondansetron, 3-10 nmol/paw), 5-HT4 ([1-[2-methylsulphonylamino ethyl]-4-piperidinyl]methyl 1-methyl-1H-indole-3-carboxylate, GR-113808, 3-100 fmol/paw), 5-HT6 (4-iodo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzene-sulfonamide hydrochloride, SB-258585, 3-10 pmol/paw) and 5-HT7 ((R)-3-(2-(2-(4-methylpiperidin-1-yl) ethyl) pyrrolidine-1-sulfonyl) phenol hydrochloride, SB-269970, 0.3-1 nmol/paw), but not by the 5-HT1A (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate, WAY-100635, 0.3-1 nmol/paw), 5-HT1B/1D (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-1,1'-biphenyl-4-carboxamide hydrochloride hydrate, GR-127935, 0.3-1 nmol/paw), 5-HT1B (1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine hydrochloride, SB-224289, 0.3-1 nmol/paw), 5-HT1D (4-(3-chlorophenyl)-α-(diphenylmethyl)-1-piperazineethanol hydrochloride, BRL-15572, 0.3-1nmol/paw) nor 5-HT5A ((N-[2-(dimethylamino)ethyl]-N-[[4'-[[(2-phenylethyl)amino]methyl][1,1'-biphenyl]-4

Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

Directory of Open Access Journals (Sweden)

Nilgun Gurbuz

Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D-mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

Directory of Open Access Journals (Sweden)

Nilgun Gurbuz

Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D- mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

Development of a serum-free co-culture of human intestinal epithelium cell-lines (Caco-2/HT29-5M21)

Science.gov (United States)

Nollevaux, Géraldine; Devillé, Christelle; El Moualij, Benaïssa; Zorzi, Willy; Deloyer, Patricia; Schneider, Yves-Jacques; Peulen, Olivier; Dandrifosse, Guy

2006-01-01

Background The absorptive and goblet cells are the main cellular types encountered in the intestine epithelium. The cell lineage Caco-2 is a model commonly used to reproduce the features of the bowel epithelium. However, there is a strong debate regarding the value of Caco-2 cell culture to mimick in vivo situation. Indeed, some authors report in Caco-2 a low paracellular permeability and an ease of access of highly diffusible small molecules to the microvilli, due to an almost complete lack of mucus. The HT29-5M21 intestinal cell lineage is a mucin-secreting cellular population. A co-culture system carried out in a serum-free medium and comprising both Caco-2 and HT29-5M21 cells was developed. The systematic use of a co-culture system requires the characterization of the monolayer under a given experimental procedure. Results In this study, we investigated the activity and localization of the alkaline phosphatase and the expression of IAP and MUC5AC genes to determine a correlation between these markers and the cellular composition of a differentiated monolayer obtained from a mixture of Caco-2 and HT29-5M21 cells. We observed that the culture conditions used (serum-free medium) did not change the phenotype of each cell type, and produced a reproducible model. The alkaline phosphatase expression characterizing Caco-2 cells was influenced by the presence of HT29-5M21 cells. Conclusion The culture formed by 75% Caco-2 and 25% HT29-5M21 produce a monolayer containing the two main cell types of human intestinal epithelium and characterized by a reduced permeability to macromolecules. PMID:16670004

Neurochemical Correlates of Accumbal Dopamine D2 and Amygdaloid 5-HT1B Receptor Densities on Observational Learning of Aggression

Science.gov (United States)

Suzuki, Hideo; Lucas, Louis R.

2015-01-01

Social learning theory postulates that individuals learn to engage in aggressive behavior through observing an aggressive social model. Prior studies have shown that repeatedly observing aggression, also called “chronic passive exposure to aggression,” changes accumbal dopamine D2 receptor (D2R) and amygdaloid 5-HT1B receptor (5-HT1BR) densities in observers. But, the association between these outcomes remains unknown. Thus, our study used a rat paradigm to comprehensively examine the linkage between aggression, D2R density in the nucleus accumbens core (AcbC) and shell (AcbSh), and 5-HT1BR density in the medial (MeA), basomedial (BMA), and basolateral (BLA) amygdala following chronic passive exposure to aggression. Male Sprague-Dawley rats (N = 72) were passively exposed to either aggression or non-aggression acutely (1 day) or chronically (23 days). When observer rats were exposed to aggression chronically, they showed increased aggressive behavior and reduced D2R density in the bilateral AcbSh. On the other hand, exposure to aggression, regardless of exposure length, increased 5-HT1BR density in the bilateral BLA. Finally, low D2R in the AcbSh significantly interacted with high 5-HT1BR density in the BLA in predicting high levels of aggression in observer rats. Our results advance our understanding of the neurobiological mechanisms for observational learning of aggression, highlighting that dopamine-serotonin interaction, or AcbSh-BLA interaction, may contribute to a risk factor for aggression in observers who chronically witness aggressive interactions. PMID:25650085

Abrogated Freud-1/Cc2d1a Repression of 5-HT1A Autoreceptors Induces Fluoxetine-Resistant Anxiety/Depression-Like Behavior.

Science.gov (United States)

Vahid-Ansari, Faranak; Daigle, Mireille; Manzini, M Chiara; Tanaka, Kenji F; Hen, René; Geddes, Sean D; Béïque, Jean-Claude; James, Jonathan; Merali, Zul; Albert, Paul R

2017-12-06

Freud-1/Cc2d1a represses the gene transcription of serotonin-1A (5-HT1A) autoreceptors, which negatively regulate 5-HT tone. To test the role of Freud-1 in vivo , we generated mice with adulthood conditional knock-out of Freud-1 in 5-HT neurons ( cF1ko ). In cF1ko mice, 5-HT1A autoreceptor protein, binding and hypothermia response were increased, with reduced 5-HT content and neuronal activity in the dorsal raphe. The cF1ko mice displayed increased anxiety- and depression-like behavior that was resistant to chronic antidepressant (fluoxetine) treatment. Using conditional Freud-1/5-HT1A double knock-out ( cF1/1A dko ) to disrupt both Freud-1 and 5-HT1A genes in 5-HT neurons, no increase in anxiety- or depression-like behavior was seen upon knock-out of Freud-1 on the 5-HT1A autoreceptor-negative background; rather, a reduction in depression-like behavior emerged. These studies implicate transcriptional dysregulation of 5-HT1A autoreceptors by the repressor Freud-1 in anxiety and depression and provide a clinically relevant genetic model of antidepressant resistance. Targeting specific transcription factors, such as Freud-1, to restore transcriptional balance may augment response to antidepressant treatment. SIGNIFICANCE STATEMENT Altered regulation of the 5-HT1A autoreceptor has been implicated in human anxiety, major depression, suicide, and resistance to antidepressants. This study uniquely identifies a single transcription factor, Freud-1, as crucial for 5-HT1A autoreceptor expression in vivo Disruption of Freud-1 in serotonin neurons in mice links upregulation of 5-HT1A autoreceptors to anxiety/depression-like behavior and provides a new model of antidepressant resistance. Treatment strategies to reestablish transcriptional regulation of 5-HT1A autoreceptors could provide a more robust and sustained antidepressant response. Copyright © 2017 the authors 0270-6474/17/3711967-12$15.00/0.

Tokamaks - Third Edition

International Nuclear Information System (INIS)

Rogister, A L

2004-01-01

John Wesson's well known book, now re-edited for the third time, provides an excellent introduction to fusion oriented plasma physics in tokamaks. The author's task was a very challenging one, for a confined plasma is a complex system characterised by a variety of dimensionless parameters and its properties change qualitatively when certain threshold values are reached in this multi-parameter space. As a consequence, theoretical description is required at different levels, which are complementary: particle orbits, kinetic and fluid descriptions, but also intuitive and empirical approaches. Theory must be carried out on many fronts: equilibrium, instabilities, heating, transport etc. Since the properties of the confined plasma depend on the boundary conditions, the physics of plasmas along open magnetic field lines and plasma surface interaction processes must also be accounted for. Those subjects (and others) are discussed in depth in chapters 2-9. Chapter 1 mostly deals with ignition requirements and the tokamak concept, while chapter 14 provides a list of useful relations: differential operators, collision times, characteristic lengths and frequencies, expressions for the neoclassical resistivity and heat conduction, the bootstrap current etc. The presentation is sufficiently broad and thorough that specialists within tokamak research can either pick useful and up-to-date information or find an authoritative introduction into other areas of the subject. It is also clear and concise so that it should provide an attractive and accurate initiation for those wishing to enter the field and for outsiders who would like to understand the concepts and be informed about the goals and challenges on the horizon. Validation of theoretical models requires adequately resolved experimental data for the various equilibrium profiles (clearly a challenge in the vicinity of transport barriers) and the fluctuations to which instabilities give rise. Chapter 10 is therefore devoted to

Three novel tokamak plasma regimes in TFTR

International Nuclear Information System (INIS)

Furth, H.P.

1985-10-01

Aside from extending ''standard'' ohmic and neutral beam heating studies to advanced plasma parameters, TFTR has encountered a number of special plasma regimes that have the potential to shed new light on the physics of tokamak confinement and the optimal design of future D-T facilities: (1) High-powered, neutral beam heating at low plasma densities can maintain a highly reactive hot-ion population (with quasi-steady-state beam fueling and current drive) in a tokamak configuration of modest bulk-plasma confinement requirements. (2) Plasma displacement away from limiter contact lends itself to clarification of the role of edge-plasma recycling and radiation cooling within the overall pattern of tokamak heat flow. (3) Noncentral auxiliary heating (with a ''hollow'' power-deposition profile) should serve to raise the central tokamak plasma temperature without deterioration of central region confinement, thus facilitating the study of alpha-heating effects in TFTR. The experimental results of regime (3) support the theory that tokamak profile consistency is related to resistive kink stability and that the global energy confinement time is determined by transport properties of the plasma edge region

Large Aspect Ratio Tokamak Study

International Nuclear Information System (INIS)

Reid, R.L.; Holmes, J.A.; Houlberg, W.A.; Peng, Y.K.M.; Strickler, D.J.; Brown, T.G.; Wiseman, G.W.

1980-06-01

The Large Aspect Ratio Tokamak Study (LARTS) at Oak Ridge National Laboratory (ORNL) investigated the potential for producing a viable longburn tokamak reactor by enhancing the volt-second capability of the ohmic heating transformer through the use of high aspect ratio designs. The plasma physics, engineering, and economic implications of high aspect ratio tokamaks were assessed in the context of extended burn operation. Using a one-dimensional transport code plasma startup and burn parameters were addressed. The pulsed electrical power requirements for the poloidal field system, which have a major impact on reactor economics, were minimized by optimizing the startup and shutdown portions of the tokamak cycle. A representative large aspect ratio tokamak with an aspect ratio of 8 was found to achieve a burn time of 3.5 h at capital cost only approx. 25% greater than that of a moderate aspect ratio design tokamak

Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

DEFF Research Database (Denmark)

Paterson, Louise M; Tyacke, Robin J; Nutt, David J

2010-01-01

Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron......, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT(1A), 5-HT(2A), and 5-HT(4) receptors and the serotonin reuptake transporter...... have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made...

A generic access to shot-based data for European Tokamaks

Energy Technology Data Exchange (ETDEWEB)

Signoret, J.; Imbeaux, F. [Association EURATOM-CEA, CEA / DSM / Institut de Recherche sur la Fusion par confinement Magnetique, CEA-Cadarache, 13 - ST-Paul-Lez-Durance (France)

2009-07-01

The EFDA Integrated Tokamak Modeling Task Force has defined a data structure offering a generic representation of the properties of physics problems and tokamak subsystem characteristics. It gathers the hardware description, modeling results and data measured during experiments, structured in terms of Consistent Physical Objects (CPOs). A generic tool has been developed to retrieve shot-based data from the various European tokamak databases: Exp2ITM. A tokamak specific XML 'mapping file' is used to map the local data formats to the ITM (Integrated Tokamak Modeling) data format. Exp2ITM is then dynamically generated from the ITM data structure and uses generic procedures to import the shot-based data. Successful tests show we have managed to import into the ITM DB experimental data from Jet and Tore-Supra. This document is a poster. (authors)

Disturbance of serotonin 5HT2 receptors in remitted patients suffering from hereditary depressive disorder.

Science.gov (United States)

Larisch, R; Klimke, A; Mayoral, F; Hamacher, K; Herzog, H R; Vosberg, H; Tosch, M; Gaebel, W; Rivas, F; Coenen, H H; Müller-Gärtner, H W

2001-08-01

The characteristics of 5HT2 receptor binding were investigated in major depression in vivo using positron emission tomography and the radioligand F-18-altanserin. Twelve patients from families with high loading of depression living in a geographically restricted region were examined and compared with normal control subjects. At the time of the PET measurement all patients were remitted; in some of them remission was sustained by antidepressive medication. Binding potential was assessed by Logan's graphical analysis method. The binding of F-18-altanserin was about 38% lower in patients than in healthy controls (p depression rather than by medication. The data suggest that 5HT2 receptors are altered in depression. We present evidence for a reduction of the receptor density, which might be usable as trait marker of subjects susceptible for depressive illness.

Prospects for Tokamak Fusion Reactors

International Nuclear Information System (INIS)

Sheffield, J.; Galambos, J.

1995-01-01

This paper first reviews briefly the status and plans for research in magnetic fusion energy and discusses the prospects for the tokamak magnetic configuration to be the basis for a fusion power plant. Good progress has been made in achieving fusion reactor-level, deuterium-tritium (D-T) plasmas with the production of significant fusion power in the Joint European Torus (up to 2 MW) and the Tokamak Fusion Test Reactor (up to 10 MW) tokamaks. Advances on the technologies of heating, fueling, diagnostics, and materials supported these achievements. The successes have led to the initiation of the design phases of two tokamaks, the International Thermonuclear Experimental Reactor (ITER) and the US Toroidal Physics Experiment (TPX). ITER will demonstrate the controlled ignition and extended bum of D-T plasmas with steady state as an ultimate goal. ITER will further demonstrate technologies essential to a power plant in an integrated system and perform integrated testing of the high heat flux and nuclear components required to use fusion energy for practical purposes. TPX will complement ITER by testing advanced modes of steady-state plasma operation that, coupled with the developments in ITER, will lead to an optimized demonstration power plant

Transient failure behavior of HT9

International Nuclear Information System (INIS)

Huang, F.H.

1994-07-01

Alloy HT9 has-been chosen as candidate materials for fast and fusion reactor applications because the.material exhibits excellent resistance to void swelling. However, ferritic alloys are known to undergo a ductile-brittle transition as the test temperature is decreased. This inherent problem has limited their applications to reactor component materials subjected to low neutron exposures. Despite the ductile-brittle transition problem, results show that the materials exhibit superior resistance to fracture under very high neutron fluences at irradiation temperatures above 380C. Results also show that the transient behavior for HT9 cladding specimens taken from the fuel column region and cladding taken from outside the fuel column or unirradiated cladding are the same. HT9 cladding maintained its transient strength with irradiation to a fluence of 9 x 10 22 n/cm 2 (E > 0.1 MeV)

Impulsive traits and 5-HT2A receptor promoter polymorphism in alcohol dependents: possible association but no influence of personality disorders.

Science.gov (United States)

Preuss, U W; Koller, G; Bondy, B; Bahlmann, M; Soyka, M

2001-01-01

Impulsive behavior in alcoholics puts them at serious risk of severer course of disease and has been related to the serotonergic neurotransmission dysfunction. The aim of this study is to investigate the association between impulsive aggression in alcohol dependents with regard to the G-1438A polymorphism in the promoter region of the 5-HT2A receptor gene. Furthermore, we investigated the statistical interaction between 5-HT2A alleles, antisocial personality disorder (APD) and impulsive aggression in alcohol dependents. Alcohol dependents were investigated because these personality disorders and impulsive behavior are very frequent in alcohol dependence anf of clinical relevance. One hundred and thirty-five patients of German descent meeting DSM-IV criteria of alcohol dependence were recruited. Blood samples were taken from alcohol dependents to determine 5-HT2A promoter polymorphisms using PCR (polymerase chain reaction) of lymphocyte DNA. Impulsive aggression was assessed using a German version of the Barratt Impulsiveness Scale which was translated and backtranslated. Alcohol dependents were subdivided into low- or high-impulsivity groups using a median split of the Barratt score. APD and borderline personality disorder (BPD) were assessed using the SCID-II interview. The low-impulsivity group was slightly older and showed a later age at alcoholism onset than the highly impulsive group. Alcohol dependents with high impulsive traits showed a significant association with 5-HT2A 1438 A alleles. After excluding alcohol dependents with APD or BPD from the analysis, this association remained significant. Furthermore, no association between APD, BPD and 5-HT2A alleles was noted. Inpatient alcohol dependents showed a significant association between 5-HT2A A alleles and impulsive traits, independent of the presence of APD or BPD. No association was noted between personality disorders and the polymorphism. This is the first report about an association of 5-HT2A promoter

Reversal of sibutramine-induced anorexia with a selective 5-HT(2C) receptor antagonist.

Science.gov (United States)

Higgs, Suzanne; Cooper, Alison J; Barnes, Nicholas M

2011-04-01

The monoamine reuptake inhibitor sibutramine reduces food intake but the receptor subtypes mediating the effects of sibutramine on feeding remain to be clearly identified. The involvement of the 5-HT(2C) receptor subtype in the satiety-enhancing effects of sibutramine was investigated by examining the effects of co-administration of sibutramine with the selective 5-HT(2C) receptor antagonist SB 242084 Microstructural analyses of licking for a glucose solution by non-deprived, male rats were performed over a range of doses of sibutramine to identify a selective satiety-enhancing dose (experiment 1). Similar analyses were performed after administration of a vehicle control, two doses of SB 242084 alone or two doses of SB 242084 in combination with sibutramine (experiment 2). Sibutramine at doses of 1-3 mg/kg selectively reduced glucose consumption via a reduction in the number of bouts of licking. Non-selective effects to increase latency to lick were only observed at the higher dose of 6 mg/kg. Co-administration of sibutramine (3 mg/kg) with SB 242084 (1 or 3 mg/kg) reversed the effect of sibutramine on bout number whereas either dose of SB 242084 alone had no significant effect. We confirm behaviourally selective effects of sibutramine on feeding and provide further support for the satiety-enhancing effects of sibutramine. Our data also provide evidence for the involvement of the 5-HT(2C) receptor in the satiety-enhancing effects of sibutramine although additional targets may have an impact, and further investigation of the molecular mechanisms underlying the efficacy of sibutramine as an anorectic is warranted.

Maternal aggression in Wistar rats: effect of 5-HT2A/2C receptor agonist and antagonist microinjected into the dorsal periaqueductal gray matter and medial septum

Directory of Open Access Journals (Sweden)

Almeida R.M.M. de

2005-01-01

Full Text Available The objective of the present study was to assess the role of the 5-HT2A/2C receptor at two specific brain sites, i.e., the dorsal periaqueductal gray matter (DPAG and the medial septal (MS area, in maternal aggressive behavior after the microinjection of either a 5-HT2A/2C receptor agonist or antagonist. Female Wistar rats were microinjected on the 7th postpartum day with the selective agonist alpha-methyl-5-hydroxytryptamine maleate (5-HT2A/2C or the antagonist 5-HT2A/2C, ketanserin. The agonist was injected into the DPAG at 0.2 (N = 9, 0.5 (N = 10, and 1.0 µg/0.2 µl (N = 9, and the antagonist was injected at 1.0 µg/0.2 µl (N = 9. The agonist was injected into the medial septal area (MS at 0.2 (N = 9, 0.5 (N = 7, and 1.0 µg/0.2 µl (N = 6 and the antagonist was injected at 1.0 µg/0.2 µl (N = 5. For the control, saline was injected into the DPAG (N = 7 and the MS (N = 12. Both areas are related to aggressive behavior and contain a high density of 5-HT receptors. Non-aggressive behaviors such as horizontal locomotion (walking and social investigation and aggressive behaviors such as lateral threat (aggressive posture, attacks (frontal and lateral, and biting the intruder were analyzed when a male intruder was placed into the female resident's cage. For each brain area studied, the frequency of the behaviors was compared among the various treatments by analysis of variance. The results showed a decrease in maternal aggressive behavior (number of bites directed at the intruder after microinjection of the agonist at 0.2 and 1.0 µg/0.2 µl (1.6 ± 0.7 and 0.9 ± 0.3 into the DPAG compared to the saline group (5.5 ± 1.1. There was no dose-response relationship with the agonist. The present findings suggest that the 5-HT2A/2C receptor agonist has an inhibitory effect on maternal aggressive behavior when microinjected into the DPAG and no effect when microinjected into the MS. Ketanserin (1.0 µg/0.2 µl decreased locomotion when microinjected

Humans Can Taste Glucose Oligomers Independent of the hT1R2/hT1R3 Sweet Taste Receptor.

Science.gov (United States)

Lapis, Trina J; Penner, Michael H; Lim, Juyun

2016-08-23

It is widely accepted that humans can taste mono- and disaccharides as sweet substances, but they cannot taste longer chain oligo- and polysaccharides. From the evolutionary standpoint, the ability to taste starch or its oligomeric hydrolysis products would be highly adaptive, given their nutritional value. Here, we report that humans can taste glucose oligomer preparations (average degree of polymerization 7 and 14) without any other sensorial cues. The same human subjects could not taste the corresponding glucose polymer preparation (average degree of polymerization 44). When the sweet taste receptor was blocked by lactisole, a known sweet inhibitor, subjects could not detect sweet substances (glucose, maltose, and sucralose), but they could still detect the glucose oligomers. This suggests that glucose oligomer detection is independent of the hT1R2/hT1R3 sweet taste receptor. Human subjects described the taste of glucose oligomers as "starchy," while they describe sugars as "sweet." The dose-response function of glucose oligomer was also found to be indistinguishable from that of glucose on a molar basis. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding

Science.gov (United States)

Mc Mahon, Brenda; MacDonald Fisher, Patrick; Jensen, Peter Steen; Svarer, Claus; Moos Knudsen, Gitte

2016-01-01

Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [11C]SB207145 for quantification of brain 5-HT4R binding. The Buss–Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. PMID:26772668

Magnetic confinement experiment. I: Tokamaks

International Nuclear Information System (INIS)

Goldston, R.J.

1995-08-01

Reports were presented at this conference of important advances in all the key areas of experimental tokamak physics: Core Plasma Physics, Divertor and Edge Physics, Heating and Current Drive, and Tokamak Concept Optimization. In the area of Core Plasma Physics, the biggest news was certainly the production of 9.2 MW of fusion power in the Tokamak Fusion Test Reactor, and the observation of unexpectedly favorable performance in DT plasmas. There were also very important advances in the performance of ELM-free H- (and VH-) mode plasmas and in quasi-steady-state ELM'y operation in JT-60U, JET, and DIII-D. In all three devices ELM-free H-modes achieved nTτ's ∼ 2.5x greater than ELM'ing H-modes, but had not been sustained in quasi-steady-state. Important progress has been made on the understanding of the physical mechanism of the H-mode in DIII-D, and on the operating range in density for the H-mode in Compass and other devices

Cerebral 5-HT2A receptor binding, but not mGluR2, is increased in tryptophan hydroxylase 2 decrease-of-function mice

DEFF Research Database (Denmark)

Jørgensen, Christinna Vangsgaard; Jacobsen, Jacob P; Caron, Marc G

2013-01-01

Transgenic mice with a knock-in (KI) of a tryptophan hydroxylase 2 (Tph2) R439H mutation, analogous to the Tph2 R441H single-nucleotide polymorphism originally identified in a late life depression cohort, have markedly reduced levels of 5-hydroxytryptamine (5-HT). These Tph2KI mice are therefore...

Fusion potential for spherical and compact tokamaks

International Nuclear Information System (INIS)

Sandzelius, Mikael

2003-02-01

The tokamak is the most successful fusion experiment today. Despite this, the conventional tokamak has a long way to go before being realized into an economically viable power plant. In this master thesis work, two alternative tokamak configurations to the conventional tokamak has been studied, both of which could be realized to a lower cost. The fusion potential of the spherical and the compact tokamak have been examined with a comparison of the conventional tokamak in mind. The difficulties arising in the two configurations have been treated from a physical point of view concerning the fusion plasma and from a technological standpoint evolving around design, materials and engineering. Both advantages and drawbacks of either configuration have been treated relative to the conventional tokamak. The spherical tokamak shows promising plasma characteristics, notably a high β-value but have troubles with high heat loads and marginal tritium breeding. The compact tokamak operates at a high plasma density and a high magnetic field enabling it to be built considerably smaller than any other tokamak. The most notable down-side being high heat loads and neutron transport problems. With the help of theoretical reactor studies, extrapolating from where we stand today, it is conceivable that the spherical tokamak is closer of being realized of the two. But, as this study shows, the compact tokamak power plant concept offers the most appealing prospect

Fusion potential for spherical and compact tokamaks

Energy Technology Data Exchange (ETDEWEB)

Sandzelius, Mikael

2003-02-01

The tokamak is the most successful fusion experiment today. Despite this, the conventional tokamak has a long way to go before being realized into an economically viable power plant. In this master thesis work, two alternative tokamak configurations to the conventional tokamak has been studied, both of which could be realized to a lower cost. The fusion potential of the spherical and the compact tokamak have been examined with a comparison of the conventional tokamak in mind. The difficulties arising in the two configurations have been treated from a physical point of view concerning the fusion plasma and from a technological standpoint evolving around design, materials and engineering. Both advantages and drawbacks of either configuration have been treated relative to the conventional tokamak. The spherical tokamak shows promising plasma characteristics, notably a high {beta}-value but have troubles with high heat loads and marginal tritium breeding. The compact tokamak operates at a high plasma density and a high magnetic field enabling it to be built considerably smaller than any other tokamak. The most notable down-side being high heat loads and neutron transport problems. With the help of theoretical reactor studies, extrapolating from where we stand today, it is conceivable that the spherical tokamak is closer of being realized of the two. But, as this study shows, the compact tokamak power plant concept offers the most appealing prospect.

Commissioning and preliminary operation of HL-2A tokamak

International Nuclear Information System (INIS)

Liu Dequan; Liu Yong; Yan Jianchen; Cao Zeng; Yang Qingwei; Zhou Caipin; Li Xiaodong

2005-01-01

HL-2A is a divertor tokamak located at new site of Southwestern Institute of Physics (SWIP), Chengdu, China. It can be operated in double-null and single-null divertor with closed configurations. The effects of the divertor on impurity behaviors, MHD instabilities, transport, wall conditioning and divertor physics are key issues to be studied during the first step operation on HL-2A. Preliminary experiments with limiter and single null divertor configurations were carried out in 2003. Main parameters achieved are the plasma current 168 KA, duration time of 920 ms and plasma linear-averaged density of 1.7 x 10 19 m -3 . The impurities, especially of low Z, are clearly decreased during the divertor experiments

Study on fast ion loss in HL-2A tokamak

International Nuclear Information System (INIS)

Liu Yi; Sun Tengfei; Ji Xiaoquan

2012-01-01

Experiments with a high-energy deuterium neutral beam (NB) injection (30 keV, about 0.6 MW) were performed on the HL-2A tokamak. Analysis of neutron decay following the NB 'blip' injection indicates that tangentially injected beam ions are well confined, slowing down classically in the HL-2A. Anomalous losses of beam ions were observed when a beta-induced Alfven acoustic (BAAE) mode was present in the plasma. Such a high energetic particle driven mode led to fast-ion loss, showing a strong influence of the energetic particle driven mode on the fast-ion transport. (authors)

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding

DEFF Research Database (Denmark)

da Cunha-Bang, Sofi; Mc Mahon, Brenda; Fisher, Patrick MacDonald

2016-01-01

of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145......Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels...... for quantification of brain 5-HT4R binding. The Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well...

J/sub 1c/ fracture toughness transition behavior of HT-9

International Nuclear Information System (INIS)

Huang, F.H.

1984-01-01

Small compact tension specimens of two heats of HT-9 were tested at temperatures ranging from room temperature to -192 0 C. The ductile-brittle transition toughness of HT-9 was evaluated using the J-integral approach. There were two loading rates of 2.1 x 10 -5 m/s and 3.2 x 10 -2 m/s. The ductile-brittle transition temperatures of HT-9 (number 1 heat) tested at 2.1 x 10 -5 m/s and HT-9 (number 2 heat) tested at 3.2 x 10 -2 m/s were found to be -60 and -10 0 C, respectively. Results showed the fracture toughness of the former was not sensitive to loading rate and the lower shelf toughness decreased with temperature to a J/sub 1c/ value of 5 kJ/m 2 at -190 0 C. Furthermore, the values of J/sub 1c/ were valid since the thickness of the test specimens was well above the thickness criterion

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding.

Science.gov (United States)

da Cunha-Bang, Sofi; Mc Mahon, Brenda; Fisher, Patrick MacDonald; Jensen, Peter Steen; Svarer, Claus; Knudsen, Gitte Moos

2016-04-01

Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145 for quantification of brain 5-HT4R binding. The Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Development of a serum-free co-culture of human intestinal epithelium cell-lines (Caco-2/HT29-5M21

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Schneider Yves-Jacques

2006-05-01

Full Text Available Abstract Background The absorptive and goblet cells are the main cellular types encountered in the intestine epithelium. The cell lineage Caco-2 is a model commonly used to reproduce the features of the bowel epithelium. However, there is a strong debate regarding the value of Caco-2 cell culture to mimick in vivo situation. Indeed, some authors report in Caco-2 a low paracellular permeability and an ease of access of highly diffusible small molecules to the microvilli, due to an almost complete lack of mucus. The HT29-5M21 intestinal cell lineage is a mucin-secreting cellular population. A co-culture system carried out in a serum-free medium and comprising both Caco-2 and HT29-5M21 cells was developed. The systematic use of a co-culture system requires the characterization of the monolayer under a given experimental procedure. Results In this study, we investigated the activity and localization of the alkaline phosphatase and the expression of IAP and MUC5AC genes to determine a correlation between these markers and the cellular composition of a differentiated monolayer obtained from a mixture of Caco-2 and HT29-5M21 cells. We observed that the culture conditions used (serum-free medium did not change the phenotype of each cell type, and produced a reproducible model. The alkaline phosphatase expression characterizing Caco-2 cells was influenced by the presence of HT29-5M21 cells. Conclusion The culture formed by 75% Caco-2 and 25% HT29-5M21 produce a monolayer containing the two main cell types of human intestinal epithelium and characterized by a reduced permeability to macromolecules.

Novel pyridylmethylamines as highly selective 5-HT(1A) superagonists.

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Bollinger, Stefan; Hübner, Harald; Heinemann, Frank W; Meyer, Karsten; Gmeiner, Peter

2010-10-14

To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT(1A) binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT(2), α(1), and α(2)-adrenergic as well as D(1)-D(4) dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT(1A) were examined in vitro employing a GTPγS assay. The investigation guided us to highly selective 5HT(1A) superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT(1A) recognition with a K(i) value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.

Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells.

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Galindo, Liliana; Moreno, Estefanía; López-Armenta, Fernando; Guinart, Daniel; Cuenca-Royo, Aida; Izquierdo-Serra, Mercè; Xicota, Laura; Fernandez, Cristina; Menoyo, Esther; Fernández-Fernández, José M; Benítez-King, Gloria; Canela, Enric I; Casadó, Vicent; Pérez, Víctor; de la Torre, Rafael; Robledo, Patricia

2018-01-02

Cannabinoid CB1 receptors (CB 1 R) and serotonergic 2A receptors (5HT 2A R) form heteromers in the brain of mice where they mediate the cognitive deficits produced by delta-9-tetrahydrocannabinol. However, it is still unknown whether the expression of this heterodimer is modulated by chronic cannabis use in humans. In this study, we investigated the expression levels and functionality of CB 1 R-5HT 2A R heteromers in human olfactory neuroepithelium (ON) cells of cannabis users and control subjects, and determined their molecular characteristics through adenylate cyclase and the ERK 1/2 pathway signaling studies. We also assessed whether heteromer expression levels correlated with cannabis consumption and cognitive performance in neuropsychological tests. ON cells from controls and cannabis users expressed neuronal markers such as βIII-tubulin and nestin, displayed similar expression levels of genes related to cellular self-renewal, stem cell differentiation, and generation of neural crest cells, and showed comparable Na + currents in patch clamp recordings. Interestingly, CB 1 R-5HT 2A R heteromer expression was significantly increased in cannabis users and positively correlated with the amount of cannabis consumed, and negatively with age of onset of cannabis use. In addition, a negative correlation was found between heteromer expression levels and attention and working memory performance in cannabis users and control subjects. Our findings suggest that cannabis consumption regulates the formation of CB 1 R-5HT 2A R heteromers, and may have a key role in cognitive processing. These heterodimers could be potential new targets to develop treatment alternatives for cognitive impairments.

Microwave Tokamak Experiment

International Nuclear Information System (INIS)

Anon.

1988-01-01

The Microwave Tokamak Experiment, now under construction at the Laboratory, will use microwave heating from a free-electron laser. The intense microwave pulses will be injected into the tokamak to realize several goals, including a demonstration of the effects of localized heat deposition within magnetically confined plasma, a better understanding of energy confinement in tokamaks, and use of the new free-electron laser technology for plasma heating. The experiment, soon to be operational, provides an opportunity to study dense plasmas heated by powers unprecedented in the electron-cyclotron frequency range required by the especially high magnetic fields used with the MTX and needed for reactors. 1 references, 5 figures, 3 tables

The ARIES tokamak fusion reactor study

International Nuclear Information System (INIS)

Bartlit, J.R.; Bathke, C.G.; Krakowski, R.A.; Miller, R.L.; Beecraft, W.R.; Hogan, J.T.; Peng, Y.K.M.; Reid, R.L.; Strickler, D.J.; Whitson, J.C.; Blanchard, J.P.; Emmert, G.A.; Santarius, J.F.; Sviatoslavsky, I.N.; Wittenberg, L.J.

1989-01-01

The ARIES study is a community effort to develop several visions of the tokamak as fusion power reactors. The aims are to determine their potential economics, safety, and environmental features and to identify physics and technology areas with the highest leverage for achieving the best tokamak reactor. Three ARIES visions are planned, each having a different degree of extrapolation from the present data base in physics and technology. The ARIES-I design assumes a minimum extrapolation from current tokamak physics (e.g., 1st stability) and incorporates technological advances that can be available in the next 20 to 30 years. ARIES-II is a DT-burning tokamak in 2nd stability regime and employs both potential advances in the physics and expected advances in technology and engineering; and ARIES-III is a conceptual D 3 He reactor. This paper focuses on the ARIES-I design. Parametric systems studies show that the optimum 1st stability tokamak has relatively low plasma current (∼ 12 MA), high plasma aspect ratio (∼ 4-6), and high magnetic field (∼ 24 T at the coil). ARIES-I is 1,000 MWe (net) reactor with a plasma major radius of 6.5 m, a minor radius of 1.4 m, a neutron wall loading of about 2.8 MW/m 2 , and a mass power density of about 90 kWe/ton. The ARIES-I reactor operates at steady state using ICRF fast waves to drive current in the plasma core and lower-hybrid waves for edge-plasma current drive. The current-drive system supplements a significant (∼ 57%) bootstrap current contribution. The impurity control system is based on high-recycling poloidal divertors. Because of the high field and large Lorentz forces in the toroidal-field magnets, innovative approaches with high-strength materials and support structures are used. 24 refs., 4 figs., 1 tab

Advanced Tokamak Stability Theory

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Zheng, Linjin

2015-03-01

The intention of this book is to introduce advanced tokamak stability theory. We start with the derivation of the Grad-Shafranov equation and the construction of various toroidal flux coordinates. An analytical tokamak equilibrium theory is presented to demonstrate the Shafranov shift and how the toroidal hoop force can be balanced by the application of a vertical magnetic field in tokamaks. In addition to advanced theories, this book also discusses the intuitive physics pictures for various experimentally observed phenomena.

In vivo binding of 125I-LSD to serotonin 5-HT2 receptors in mouse brain

International Nuclear Information System (INIS)

Hartig, P.R.; Scheffel, U.; Frost, J.J.; Wagner, H.N. Jr.

1985-01-01

The binding of 125 I-LSD (2-[ 125 I]-lysergic acid diethylamide) was studied in various mouse brain regions following intravenous injection of the radioligand. The high specific activity of 125 I-LSD enabled the injection of low mass doses (14ng/kg), which are well below the threshold for induction of any known physiological effect of the probe. The highest levels of 125 I-LSD binding were found in the frontal cortex, olfactory tubercles, extra-frontal cortex and striatum while the lowest level was found in the cerebellum. Binding was saturable in the frontal cortex but increased linearly in the cerebellum with increasing doses of 125 I-LSD. Serotonergic compounds potently inhibited 125 I-LSD binding in cortical regions, olfactory tubercles, and hypothalamus but had no effect in the cerebellum. Dopaminergic compounds caused partial inhibition of binding in the striatum while adrenergic compounds were inactive. From these studies the authors conclude that 125 I-LSD labels serotonin 5-HT 2 receptor sites in cortical regions with no indication that other receptor sites are labeled. In the olfactory tubercles and hypothalamus, 125 I-LSD labeling occurs predominantly or entirely at serotonic 5-HT 2 sites. In the striatum, 125 I-LSD labels approximately equal proportions of serotonergic and dopaminergic sites. These data indicate that 125 I-LSD labels serotonin receptors in vivo and suggests that appropriate derivatives of 2I-LSD may prove useful for tomographic imaging of serotonin 5-HT 2 receptors in the mammalian cortex