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Sample records for ht-7 tokamak

  1. Measurement of the runaway electrons in the HT-7 tokamak

    SciTech Connect

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

    2006-01-15

    A thermographic camera and four hard x-ray detectors have been developed to measure the runaway electrons in the HT-7 tokamak. The synchrotron radiation originated from the runaway electrons was measured by an infrared (IR) camera working in the wavelength ranges of 7.5-13 {mu}m. With a tangential viewing into the plasma in the direction of the electron approach on the equatorial plane, the synchrotron radiation from the runaway electrons was measured in a full poloidal cross section. Three NaI scintillators are used to monitor the hard x-ray radiation (HXR) in the energy ranges of 0.5-7 MeV, and a CdTe detector is used to monitor the low-energy HXR in the energy ranges of 0.3-1.2 MeV. The combination of infrared camera and hard x-ray detectors provides a powerful tool to investigate the runaway electron dynamics in HT-7. Runaways in the core and edge regions are monitored simultaneously. The parameters of runaway beam in the core are deduced from the IR pictures. The interaction of runway electrons with toroidal magnetic field ripple is monitored from the HXR emission.

  2. Optical Design of ECEI Diagnostic System for HT-7 Tokamak

    NASA Astrophysics Data System (ADS)

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

    2004-02-01

    Electron cyclotron emission imaging system in the frequency range of 95 GHz-125 GHz is going to be constructed for a two-dimensional diagnosis of the electron temperature profiles and fluctuations on the HT-7 Tokamak. The optical design for the ECEI diagnostic system is completed. Because of the superconducting technology used in HT-7, the vacuum chamber is rather thick (630 mm), the height of the horizontal windows is limited (maximum 450 mm), which constrains greatly the ECE imaging Gaussian beam that passing through the windows. We here comes to make a design compromise between the number of the beams that can pass through the windows and the spatial resolution (around 1.1 cm). We also find that due to the field curvature of the optical system, the gaussian beams of edge channels are always overlapped. To flatten the field curvature, it is needed to insert a concave made of a material with a low refractive index (compared with the one used in the convex). But the suitable material has not been available so far, therefore the deterioration of the resolution in some channels (e.g. the edge channels) is acceptable.

  3. Enhanced Lower Hybrid Current Drive Experiments on HT-7 Tokamak

    NASA Astrophysics Data System (ADS)

    Shen, Wei-ci; Kuang, Guang-li; Liu, Yue-xiu; Ding, Bo-jiang; Shi, Yao-jiang; HT-7 Team

    2003-02-01

    Effective Lower Hybrid Current Driving (LHCD) and improved confinement experiments in higher plasma parameters (Ip > 200 kA, ne > 2 × 1013 cm-3, Te >= 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 ne and toroidal magnetic field BT 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 ηCD = Ipbar neR/PRF approx 1.05 × 1019 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.

  4. Investigation of Ion Temperature Characteristics in the HT-7 Tokamak

    NASA Astrophysics Data System (ADS)

    Li, Yingying; Fu, Jia; Shi, Yuejiang; Wang, Fudi; Zhang, Wei; Ti, Ang; Xu, Ping; Huang, Yiyun; Hu, Chundong

    2011-10-01

    Characteristics of ion temperature measured with charge-exchange recombination spectroscopy (CXRS) were studied in Ohmic, lower-hybrid-wave (LHW) driven and ion-cyclotron-resonance-frequency (ICRF) heated plasmas in HT-7. The results indicate that the central ion temperature Ti0 follows the one-third power law in the product of central line-averaged density n¯e and plasma current Ip in Ohmic discharges and is therefore consistent with the Artsimovich scaling law Ti0 = K · (Ip · Bt · n¯e · R2)1/3. It is shown that there is an appreciable increase of ion temperature during the operation with both LHW and ICRF and that the increment of ion temperature in those shots is mainly due to the energy transfer via collisions between ions and electrons rather that by direct heating of the ions.

  5. Poloidal Field Power Supply Systems for the HT-7U Steady-State Superconducting Tokamak

    SciTech Connect

    Fu, P.; Liu, Z.Z.; Xu, J.Z.; Gao, G.; Wen, J.L.; Cao, Y.; Song, Z.Q.; Tang, L.J.; Wang, L.S.; Liang, X.Y.

    2002-07-15

    The paper gives a description of the poloidal field power supplies and the control system of the HT-7U superconducting tokamak required to energize the magnetic field coils for plasma excitation and confinement. An original configuration of alternating-current/direct-current (dc) converter, thyristor dc circuit breaker, and power supply control system are introduced in detail.

  6. Density Modulation Experiments to Determine Particle Transport Coefficients on HT-7 Tokamak

    NASA Astrophysics Data System (ADS)

    Jie, Yinxian; Gao, Xiang; K, Tanaka; R, Sakamoto; K, Toi; Liu, Haiqing; Gao, Li; M, Asif; Liu, Jin; Xu, Qiang; Tong, Xingde; Cheng, Yongfei

    2006-03-01

    The particle diffusion coefficient and the convection velocity were studied based on the density modulation using D2 gas puffing on the HT-7 tokamak. The density was measured by a five-channel FIR interferometer. The density modulation amplitude was 10% of the central chord averaged background density and the modulation frequency was 10 Hz in the experiments. The particle diffusion coefficient (D) and the convection velocity (V) were obtained for different background plasmas with the central chord averaged density = 1.5×1019 m-3 and 3.0×1019 m-3 respectively. It was observed that the influence of density modulation on the main plasma parameters was very weak. This technology is expected to be useful for the analysis of LHW and IBW heated plasmas on HT-7 tokamak in the near future.

  7. Poloidal beta and internal inductance measurement on HT-7 superconducting tokamak

    SciTech Connect

    Shen, B.; Sun, Y. W.; Wan, B. N.; Qian, J. P.

    2007-09-15

    Poloidal beta {beta}{sub {theta}} and internal inductance l{sub i} measurements are very important for tokamak operation. Much more plasma parameters can be inferred from the two parameters, such as the plasma energy confinement time, the plasma toroidal current profile, and magnetohydrodynamics instability. Using diamagnetic and compensation loop, combining with poloidal magnetic probe array signals, poloidal beta {beta}{sub {theta}} and internal inductance l{sub i} are measured. In this article, the measurement system and arithmetic are introduced. Different experimental results are given in different plasma discharges on HT-7 superconducting tokamak.

  8. Data processing and analysis of the imaging Thomson scattering diagnostic system on HT-7 tokamak.

    PubMed

    Han, Xiaofeng; Shao, Chunqiang; Xi, Xiaoqi; Zhao, Junyu; Qing, Zang; Yang, Jianhua; Dai, Xingxing; Kado, Shinichiro

    2013-05-01

    A high spatial resolution imaging Thomson scattering diagnostic system was developed in ASIPP (Institute of Plasma Physics, Chinese Academy of Sciences). After about one month trial running on the superconducting HT-7 (Hefei Tokamak-7) tokamak, the system was proved to be capable of measuring plasma electron temperature. The system setup and data calibration are described in this paper and then the instrument function is studied in detail, as well as the measurement capability, an electron temperature of 50 eV to 2 keV and density beyond 1 × 10(19) m(-3). Finally, the data processing method and experimental results are presented.

  9. Development of Special Winding Machine for HT-7U Superconducting Tokamak

    NASA Astrophysics Data System (ADS)

    Gao, Da-ming; Yu, Jie; Zhu, Wen-hua; Wen, Jun; Pan, Yin-nian; Chen, Le-ping; Tao, Yu-ming; Wang, Hai-jing; He, Wei

    2000-02-01

    A special winding machine with high accuracy has just been developed and applied to the construction of HT-7U Tokamak. It is one of the critical facilities for R & D of HT-7U construction. The machine mainly consists of five parts, including a CICC pay-off spool, a four-roller correcting assembly, a four-roller forming/bending assembly, a continuous winding structure and a CNC control system with three-axis AC servo motors. The facility is used for Cable in Conduit Conductor (CICC) magnet fabrication of HT-7U. The main requirements of the winding machine are: continuous winding to reduce joints inside the coils; pre-forming CICC conductor to avoid winding with tension; suitable for all TF & PF coils of various coil shapes and within the dimension limit; improving the configuration tolerance and the special flatness of the CICC conductor. This paper emphasizes on the design and fabrication of the special winding machine for HT-7U. Some analyses and techniques in winding process for trial D-shape coil are also presented.

  10. Soft x-ray pulse height analyzer in the HT-7 tokamak

    SciTech Connect

    Shi Yuejiang; Chen Zhongyong; Wan Baonian; Lv Bo; Hu Liqun; Lin Shiyao; Hu Qinsheng; Qian Jinping; Liu Haiqing; Liu Shengxia; Xu Yucun; Shan Jiafang; Li Jiangang

    2004-11-01

    A new soft x-ray pulse height analyzer (PHA), based on a Silicon Drift Detector (SDD) linear array consisting of 15 SDD detectors, has been installed in the HT-7 tokamak. The energy resolution of 150-180 eV at photon energy of 6 keV is achieved for the SDD with Peltier cooling. The effective time response of the SDD PHA is 50 ms. The profiles of electron temperature and the intensity of metallic impurities can be obtained with a spatial resolution of 3 cm. The performance and first experimental results from the new PHA system are presented.

  11. Cleaning of HT-7 Tokamak Exposed First Mirrors by Radio Frequency Magnetron Sputtering Plasma

    NASA Astrophysics Data System (ADS)

    Yan, Rong; Chen, Junling; Chen, Longwei; Ding, Rui; Zhu, Dahuan

    2014-12-01

    The stainless steel (SS) first mirror pre-exposed in the deposition-dominated environment of the HT-7 tokamak was cleaned in the newly built radio frequency (RF) magnetron sputtering plasma device. The deposition layer on the FM surface formed during the exposure was successfully removed by argon plasma with a RF power of about 80 W and a gas pressure of 0.087 Pa for 30 min. The total reflectivity of the mirrors was recovered up to 90% in the wavelength range of 300-800 nm, while the diffuse reflectivity showed a little increase, which was attributed to the increase of surface roughness in sputtering, and residual contaminants. The FMs made from single crystal materials could help to achieve a desired recovery of specular reflectivity in the future.

  12. Modification of Boundary Parameters and Fluctuations by IBW and LHCD in the HT-7 Tokamak

    NASA Astrophysics Data System (ADS)

    Song, Mei; Wan, Baonian; Xu, Guosheng; Liu, Haiqing; Ling, Bili; Li, Chengfu; Zhou, Liwu

    2003-08-01

    Measurements of boundary parameters and their fluctuations have been performed in ohmic (OH) plasma and Ion Bernstein Wave (IBW) and Lower Hybrid Current Drive (LHCD) enhanced confinement plasma using a pneumatically driven Langmuir probe array on HT-7 tokamak. In the enhanced confinement plasma, the gradients of electron density and temperature become higher and a transport barrier comes into being in the vicinity of the limiter. The boundary potential shows a clear modification in the same region. The fluctuation levels are significantly depressed and the coherences between fluctuations are reduced evidently in the enhanced plasma. Meanwhile, we obtained the spectral features and the poloidal phase velocity of fluctuations using a two-point correlation technique and found obvious modifications of the turbulence and the poloidal flow. The results suggest that the improved confinement in the IBW and LHCD enhanced plasma is at least partially due to the modification of the boundary parameters and the suppression of the boundary fluctuations and fluctuation induced fluxes.

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

    NASA Astrophysics Data System (ADS)

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

    2006-05-01

    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.

  14. Improved confinement mode induced by a MARFE during lower hybrid current drive in the HT-7 tokamak

    NASA Astrophysics Data System (ADS)

    Asif, M.; Gao, X.; HT-7 Team

    2006-04-01

    Lower hybrid current drive (LHCD) experiments have been carried out to achieve high performance for long pulse operation in the Hefei tokamak-7 (HT-7) superconducting tokamak. Multifaceted asymmetric radiation from the edge (MARFE) phenomena and an improved confinement mode induced by a MARFE are observed in LHCD plasmas when PLH>160 kW and the edge safety factor q(a) is slightly less than 6.5. It is found that an improved confinement mode induced by a MARFE, characterized by Hα line emissions drops and the line-averaged density increase is triggered in the MARFE discharges. The MARFE event occurs at t=1120 ms following the L H transition, and the improved confinement phase exists for about 65 ms from t=1140 ms after the L H transition. The LHCD plasma results basically are typical with MARFEs and it is an improved confinement mode; they are unique in that they appear at very low \\bar {n}_e values in the HT -7 tokamak.

  15. Understanding the bursty electron cyclotron emission during a sawtooth crash in the HT-7 tokamak

    SciTech Connect

    Li, Erzhong Hu, Liqun; Chen, Kaiyun

    2014-01-15

    Bursts in electron cyclotron emission (ECE) were observed during sawtooth crashes in HT-7 in discharges with ion cyclotron resonance heating injected near the q = 1 rational surface (q is the safety factor). The local ECE measurement indicated that the bursty radiation is only observed on channels near but a little away outward from the q = 1 magnetic surface. In conjunction with the soft x-ray tomography analysis, it was determined that, for the first time, only a compression process survives in the later stage of fast magnetic reconnection but before prompt heat transport. The compression enhanced the electron radiation temperature, the increased amplitude of which agreed well with the estimation according to a kinetic compression theory model [R. J. Hastie and T. C. Hender, Nucl. Fusion 28, 585 (1988)]. This paper presents the experimental evidence that there indeed exists a transient compression phase which results in the bursty ECE radiation during a sawtooth crash.

  16. Long Pulse Enhanced Confinement Discharges in the HT-7 Superconducting Tokamak by IBW Heating and LH Wave Current Drive

    NASA Astrophysics Data System (ADS)

    Li, Jiangang

    2002-11-01

    Significant progress has been made on the HT-7 superconducting tokamak in the past year toward obtaining advanced operating modes in steady state. By combining IBW and LHCD, ELM-free limiter H-mode discharges with H_89 2, β _N*H_89 > 3 have been obtained that lasted for 53% τE . A well boronized wall prevented the further impurity accumulation and the large pumping kept the recycling at a very low level. The density kept almost constant with the feedback control. The non-inductive driven current fraction is about 60% and bootstrap fraction is about 18%. The central electron temperature is about 2.6 keV and density above 2 X 10^19 m-3. With reduced plasma parameters of central Te 1.5 keV and n_e0 2 X 10^19 m-3, H_89 1.45, βN 1.1, the improved confinement phase lasts for more than 100τE with the non-inductive driven current fraction 70%. Several technical improvements, especially suitable for teady-state operation, have been made to get these long pulse, enhanced confinement discharges. The new GBST1308 doped graphite coated with a 100 μ m functional gradient coating of SiC film was used as limiter material. The tiles can withstand 5 MW/m^2 heat loads for 30 seconds with water-cooling. Twenty-four pieces of a ferromagnetic material -- ferritic steel -- have been installed to reduce the ripple at the limiter radius from 4% to less than 1.6%. Two large cry-pumps were installed to control particle exhaust. New RF wall coating techniques suitable for superconducting operation, such as RF boronization, siliconization and long-life Li coating, have been developed and routinely used in the HT-7 tokamak. This contributes to the significant reduction of the impurity radiation and edge recycling. Edge turbulence measured by Langmuir probes has been suppressed either by IBW or by LHCD for a low recycling and boronized wall. The edge electric field shear has been modified by IBW and LHCD. Transport analysis of sawtooth heat pulse propagation shows very low electron heat

  17. Study of lower hybrid current drive efficiency and its correlation with photon temperatures in the HT-7 tokamak

    NASA Astrophysics Data System (ADS)

    Younis, J.; Wan, B. N.; Lin, S. Y.; Shi, Y. J.; Ding, B. J.; Gong, X.; HT-7 Team

    2009-07-01

    Lower hybrid current drive (LHCD) efficiency is a very important parameter. The experimental current drive efficiency is defined as η = IrfneR/PLH, where Irf is the current driven by the lower hybrid waves (LHWs), ne is the central line-average density, R is the major radius of the plasma and PLH is the injected LH wave power absorbed by the plasma through Landau damping. A study of current drive efficiency of LHWs in the HT-7 tokamak has been carried out in the parameter ranges: ne = (1.2-2.5) × 1019 m-3, Ip = (80-200) kA, Bt = 1.8 T, PLH = (188-532) kW in the limiter configuration. Current drive efficiency is investigated through a simple correlation with photon temperature and normalized intensity of fast electron bremstrahlung emission, which is, in the first approximation, proportional to the averaged velocity and population of the fast electrons. The plasma current scanning experiment shows that CD efficiency increase is due to the increase in both the photon temperature and the population of the fast electrons generated by LHWs. The density scanning experiment shows that as the plasma density is increased, an increment in CD efficiency along with the increase in the population of fast electrons is observed. The slowing down through the collisions with bulk electrons is mainly responsible for the decreased photon temperature during the plasma density scan. These experiments strongly suggest the dominant role of the population of fast electrons generated by LHCD and the generation of the current carried by fast electrons.

  18. An integrative radiation protection control system based on a CAN bus for the HT-7U tokamak fusion device.

    PubMed

    Chai, Zhuxin; Huang, Qunying; Wu, Yican; Liu, Xiaoping; Liao, Zhuhua

    2004-06-01

    A radiation protection control system has been designed, based on distributed computers and consideration of the features of the radiation source of the HT-7U fusion experimental device, for protecting the workers and the public against neutron and photon radiation, and especially for ensuring that workers cannot unexpectedly enter an area of high radiation level in any case. A multisubsystem (irradiation monitoring subsystem, access control subsystem, safety interlock subsystem and other related facilities) integration concept is proposed for the design. This system has been implemented on the basis of the up-to-date industrial field bus CAN, featuring simplicity and flexibility of installation and maintenance, capability for real-time long distance communication and multi-master protocol.

  19. Electron cyclotron emission reconstruction image and m/n=3/2 mode in HT-7 tokamak

    SciTech Connect

    Li Erzhong; Hu Liqun; Ling Bili; Liu Yong; Ti Ang; Chen Kaiyun; Shen Biao; Gao Xiang

    2010-07-15

    Electron cyclotron emission reconstruction image has been used for flux surface reconstruction. The reconstruction image is based on plasma rigid rotation which is obtained from Mirnov diagnostic. From the reconstructed two-dimensional flux surface, the classical m/n=3/2 mode is visualized, which is of similar spatial structure as neoclassical 3/2 mode observed in some other tokamaks [B. Esposito et al., Phys. Rev. Lett. 100, 045006 (2008)].

  20. Control System of Neutral Beam Injection on HT-7

    NASA Astrophysics Data System (ADS)

    Wang, Yongjun; Hu, Chundong; Liu, Zhimin; Liu, Sheng; Song, Shihua; Yang, Daoye

    2005-06-01

    Neutral Beam Injection control system (NBICS) is constructed to measure the plasma current, Magnet current, vacuum pressure, cryopump temperature, control water cooling, filament voltage, and power supply, etc. The NBICS, consisting mainly of a Programmable Logic Controller (PLC) subsystem, data acquisition and processing subsystem and cryopump and vacuum pressure monitoring subsystem, has successfully been used on a NBI device. In this article, the design of NBICS on HT-7 is discussed and each subsystem is described in particular. In addition, some experimental results are reported which are very important data for further research related to the HT-7 tokamak.

  1. HT-7 Multipoint Nd Laser Thomson Scattering Apparatus

    NASA Astrophysics Data System (ADS)

    Mao, Jian-shan; Zhao, Jun-yu; Li, Ya-dong; Xie, Ai-gen; Fang, Zhi-sheng; V, Sannikov; A, Gorshkov

    2001-04-01

    A compact, low cost, multipoint Thomson scattering diagnostic system for HT-7 superconducting tokamak has been in operation since 1999. Its capability of measuring electron temperatures is in the range of 200 eV to 2 keV at a density of a few times 1012 cm-3, with a spatial resolution of 2.4 cm for 5 spatial points and a temporal resolution of 1 ms similar 1 s for 8 time points. The main components of the diagnostic system include a 20-25 J Nd:glass laser with 35 ns pulse width (8 pulses per burst), a KDP frequency-doubling unit, spherical mirrors of multipass input optical system, a wide-angle collection objective, a bandpass glass filter for reducing the stray light to zero, a f/2.5 polychromator, a fiberglass collimator, a photomultiplier's box with electronic preamplifier, high gain and high signal/noise ratio, CAMAC data acquisition and so on. The multipass optical system has been successful at increasing the quantity of scattered photons by passing the probing laser beam 10 times through the plasma under investigation. The HT-7 Thomson scattering diagnostic has provided successfully the information on two-dimensional electron temperature in the plasma of HT-7 tokamak with LHCD and IBW.

  2. Serotonergic 5-HT7 receptors and cognition.

    PubMed

    Gasbarri, Antonella; Pompili, Assunta

    2014-01-01

    The abundant distribution of serotonin (5-HT) in different areas of the central nervous system can explain the involvement of this neurotransmitter in the regulation of several functions, such as sleep, pain, feeding, and sexual and emotional behaviors. Moreover, the serotonergic system is also involved in other more complex roles, such as cognition, including learning and memory processes. Recent studies led to the discovery of various types and subtypes of receptors differentially associated to cognitive mechanisms. 5-HT7 is the most recently discovered receptor for 5-HT; therefore, it is also one of the least well characterized. Studies exist hypothesizing the role of 5-HT7 on the modulation of learning and memory processes and other cognitive functions. Moreover, much attention has been devoted to the possible role of 5-HT7 receptors in psychiatric disorders. Therefore, the aim of this review is to clarify the behavioral role of the recently discovered 5-HT7 type receptor and highlight its involvement in the cognitive functions, with particular attention to the modulation of learning and memory processes, thus providing a basis to obtain new therapeutic agents and strategies for the treatment of cognitive disorders.

  3. Inflammation and peripheral 5-HT7 receptors: the role of 5-HT7 receptors in carrageenan induced inflammation in rats.

    PubMed

    Albayrak, Abdulmecit; Halici, Zekai; Cadirci, Elif; Polat, Beyzagul; Karakus, Emre; Bayir, Yasin; Unal, Deniz; Atasoy, Mustafa; Dogrul, Ahmet

    2013-09-05

    The aim of this study was: (1) to investigate possible role for 5-HT7 receptors in carrageenan induced inflammatory paw oedema in rats; (2) to determine the presence of 5-HT7 receptors in rat paw tissue; (3) to observe the effects of 5-HT7 receptor agonist and antagonist administration on inflammation; and (4) to determine a unique mechanism for inflammatory processes via 5-HT7 receptors. Effects of 5-HT7 receptor agonist, antagonist and indomethacin were investigated in carrageenan induced paw oedema in rats. Blood and tissue samples were collected and evaluated biochemically for serum cytokine levels, tissue oxidant-antioxidant balance and histopathologically for inflammatory cell accumulation. We performed Real Time PCR analyses for tissue 5-HT7 receptor and COX mRNA expressions. The 5-HT7 receptor agonist AS-19 exerted significant anti-inflammatory effect both alone and in combination with indomethacin. Antagonist, SB269970, did not affect inflammation alone but decreased the effects of agonist when co-administered. 5-HT7 mRNA levels were higher in the carrageenan group than healthy control. Carrageenan+indometacin group decreased the mRNA expression of 5-HT7 when compared to carrageenan group. While agonist administration decreased 5-HT7 mRNA expression when compared to carrageenan group. Agonist decreased paw COX expression. Agonist also decreased serum cytokine levels and tissue oxidative stress. In conclusion, this study demonstrated for the first time that 5-HT7 receptors are expressed in rat paw tissue and that this expression responds to inflammatory stimuli. The 5-HT7 receptor may be a promising new therapeutic target for prevention of inflammation and inflammatory disorders and may also provide a new glimpse into inflammation pathophysiology.

  4. Comparison of anomalous Doppler resonance effects with molybdenum and graphite limiters on HT-7

    PubMed Central

    Wang, Y. M.; Gao, X.; Ling, B. L.; Liu, Y.; Zhang, S. B.; Han, X.; Ti, A.; Li, E. Z.

    2012-01-01

    The material of limiter in HT-7 tokamak was changed from graphite to molybdenum in the last experimental campaign. The pitch angle scattering of runaway electrons due to anomalous Doppler resonance effects was observed. The experimental results agree very well with the stable boundary condition expected from the linear resistive theory but only agree with that from the nonlinear evolutionary of runaway-electron distribution theory in low electric field region. The current carried by runaway electrons is the same under different limiter conditions. PMID:22509090

  5. Comparison of anomalous Doppler resonance effects with molybdenum and graphite limiters on HT-7.

    PubMed

    Wang, Y M; Gao, X; Ling, B L; Liu, Y; Zhang, S B; Han, X; Ti, A; Li, E Z

    2012-03-01

    The material of limiter in HT-7 tokamak was changed from graphite to molybdenum in the last experimental campaign. The pitch angle scattering of runaway electrons due to anomalous Doppler resonance effects was observed. The experimental results agree very well with the stable boundary condition expected from the linear resistive theory but only agree with that from the nonlinear evolutionary of runaway-electron distribution theory in low electric field region. The current carried by runaway electrons is the same under different limiter conditions.

  6. Aryl biphenyl-3-ylmethylpiperazines as 5-HT7 receptor antagonists.

    PubMed

    Kim, Jeeyeon; Kim, Youngjae; Tae, Jinsung; Yeom, Miyoung; Moon, Bongjin; Huang, Xi-Ping; Roth, Bryan L; Lee, Kangho; Rhim, Hyewhon; Choo, Il Han; Chong, Youhoon; Keum, Gyochang; Nam, Ghilsoo; Choo, Hyunah

    2013-11-01

    The 5-HT7 receptor (5-HT7 R) is a promising therapeutic target for the treatment of depression and neuropathic pain. The 5-HT7 R antagonist SB-269970 exhibited antidepressant-like activity, whereas systemic administration of the 5-HT7 R agonist AS-19 significantly inhibited mechanical hypersensitivity and thermal hyperalgesia. In our efforts to discover selective 5-HT7 R antagonists or agonists, aryl biphenyl-3-ylmethylpiperazines were designed, synthesized, and biologically evaluated against the 5-HT7 R. Among the synthesized compounds, 1-([2'-methoxy-(1,1'-biphenyl)-3-yl]methyl)-4-(2-methoxyphenyl)piperazine (28) was the best binder to the 5-HT7 R (pKi =7.83), and its antagonistic property was confirmed by functional assays. The selectivity profile of compound 28 was also recorded for the 5-HT7 R over other serotonin receptor subtypes, such as 5-HT1 R, 5-HT2 R, 5-HT3 R, and 5-HT6 R. In a molecular modeling study, the 2-methoxyphenyl moiety attached to the piperazine ring of compound 28 was proposed to be essential for the antagonistic function.

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

    NASA Astrophysics Data System (ADS)

    Zhuang, Huidong; Zhang, Xiaodong

    2013-08-01

    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.

  8. The serotonin 5-HT7 receptors: two decades of research.

    PubMed

    Gellynck, Evelien; Heyninck, Karen; Andressen, Kjetil W; Haegeman, Guy; Levy, Finn Olav; Vanhoenacker, Peter; Van Craenenbroeck, Kathleen

    2013-10-01

    Like most neurotransmitters, serotonin possesses a simple structure. However, the pharmacological consequences are more complex and diverse. Serotonin is involved in numerous functions in the human body including the control of appetite, sleep, memory and learning, temperature regulation, mood, behavior, cardiovascular function, muscle contraction, endocrine regulation, and depression. Low levels of serotonin may be associated with several disorders, namely increase in aggressive and angry behaviors, clinical depression, Parkinson's disease, obsessive-compulsive disorder, eating disorders, migraine, irritable bowel syndrome, tinnitus, and bipolar disease. These effects are mediated via different serotonin (5-HT) receptors. In this review, we will focus on the last discovered member of this serotonin receptor family, the 5-HT7 receptor. This receptor belongs to the G protein-coupled receptor superfamily and was cloned two decades ago. Later, different splice variants were described but no major functional differences have been described so far. All 5-HT7 receptor variants are coupled to Gαs proteins and stimulate cAMP formation. Recently, several interacting proteins have been reported, which can influence receptor signaling and trafficking.

  9. Impaired effect of activation of rat hippocampal 5-HT7 receptors, induced by treatment with the 5-HT7 receptor antagonist SB 269970.

    PubMed

    Kusek, M; Sowa, J; Tokarski, K; Hess, G

    2015-04-01

    Effects of the 5-HT(7) receptor antagonist SB 269970, administered for 14 days (1.25 mg/kg), were studied in ex vivo slices of rat hippocampus. To activate the 5-HT(7) receptor, 5-carboxamidotryptamine (5-CT, 200 nM) was applied in the presence of WAY 100635 (2 μM), a 5-HT(1A) receptor antagonist. In contrast to control preparations, no 5-HT(7) receptor-mediated increase in excitability nor depolarization and an increase in the input resistance of CA1 and CA3 pyramidal neurons were present in slices prepared from rats treated with SB 269970. The treatment also abolished the stimulatory effect of 5-HT(7) receptor activation on spontaneous excitatory postsynaptic currents recorded from CA1 stratum radiatum/lacunosum-moleculare interneurons. These data demonstrate that repeated administration of SB 269970 impairs the reactivity of the CA1 hippocampal neuronal network to 5-HT(7) receptor activation.

  10. Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7(b))

    PubMed Central

    Jasper, J R; Kosaka, A; To, Z P; Chang, D J; Eglen, R M

    1997-01-01

    The rat 5-hydroxytryptamine (5-HT)7 receptor displays two splice variations, a long form, and a truncated splice isoform, arising from the introduction of a stop codon near the carboxy-terminus. The human 5-HT7 receptor gene contains at least two introns and encodes a 445 amino acid 5-HT receptor. A truncated splice variation in the human 5-HT7 receptor was isolated from a human placental cDNA library. In accordance with current NC-IUPHAR nomenclature guidelines, it is suggested that this receptor be denoted as the h5-HT7(b) receptor and the long form of the receptor as h5-HT7(a). The h5-HT7(b) receptor was stably expressed in HEK 293 cells and ligand affinities were determined by displacement of [3H]-5-carboxyamidotryptamine (5-CT; Kd=0.28±0.06 nM, Bmax=7.3±1.7 pmol mg−1 protein). The rank order of affinities (pKi) for a series of ligands was: 5-carboxamidotryptamine (5-CT, 9.65)>5-hydroxytryptamine (5-HT, 9.41)>methiothepin (8.87)>mesulergine (7.87)>8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT, 6.85)>ketanserin (6.44). The h5-HT7(b) receptor coupled positively to adenylyl cyclase in HEK 293 cells. This response was elicited by a number of agonists with the following order of potency (pEC50): 5-CT (8.7±0.11)>5-MeOT (5-methoxytryptamine; 8.1±0.20)>5-HT (7.5±0.13)>tryptamine (5.6±0.36)>8-OH-DPAT (5.3±0.28)>5-methoxytryptamine (5.0±0.06). This rank order was comparable to that observed in the radioligand binding studies. In a similar fashion to that described for the 5-HT7(a) receptor, PCR studies suggested that the 5-HT7(b) receptor mRNA is found in great abundance throughout the brain, in the small intestine and aorta. It is concluded that the h5-HT7 receptor, like the rat receptor, exists as splice variants exhibiting similar pharmacology, signal transduction and distribution. It is thus likely that there exists a complex physiological role for alternate splicing products of the 5-HT7 receptor gene. PMID:9298538

  11. The 5-HT7 receptor is involved in allocentric spatial memory information processing.

    PubMed

    Sarkisyan, Gor; Hedlund, Peter B

    2009-08-24

    The hippocampus has been implicated in aspects of spatial memory. Its ability to generate new neurons has been suggested to play a role in memory formation. Hippocampal serotonin (5-HT) neurotransmission has also been proposed as a contributor to memory processing. Studies have shown that the 5-HT(7) receptor is present in the hippocampus in relatively high abundance. Thus the aim of the present study was to investigate the possible role of the 5-HT(7) receptor in spatial memory using 5-HT(7) receptor-deficient mice (5-HT(7)(-/-)). A hippocampus-associated spatial memory deficit in 5-HT(7)(-/-) mice was demonstrated using a novel location/novel object test. A similar reduction in novel location exploration was observed in C57BL/6J mice treated with the selective 5-HT(7) receptor antagonist SB-269970. These findings prompted an extended analysis using the Barnes maze demonstrating that 5-HT(7)(-/-) mice were less efficient in accommodating to changes in spatial arrangement than 5-HT(7)(+/+) mice. 5-HT(7)(-/-) mice had specific impairments in memory compilation required for resolving spatial tasks, which resulted in impaired allocentric spatial memory whereas egocentric spatial memory remained intact after the mice were forced to switch back from striatum-dependent egocentric to hippocampus-dependent allocentric memory. To further investigate the physiological bases underlining these behaviors we compared hippocampal neurogenesis in 5-HT(7)(+/+) and 5-HT(7)(-/-) mice employing BrdU immunohistochemistry. The rate of cell proliferation in the dentate gyrus was identical in the two genotypes. From the current data we conclude that the 5-HT(7)(-/-) mice performed by remembering a simple sequence of actions that resulted in successfully locating a hidden target in a static environment.

  12. New 1-arylindoles based serotonin 5-HT7 antagonists. Synthesis and binding evaluation studies.

    PubMed

    Sagnes, Charlène; Fournet, Guy; Satala, Grzegorz; Bojarski, Andrzej J; Joseph, Benoît

    2014-03-21

    Based on 5-HT1A and 5-HT7 ligand MR25003 scaffold, a new series of 1-aryl indole analogues were prepared and evaluated against 5-HT7 receptors. Modulations of aryl moieties provided a large number of new indolic derivatives. Most of compounds tested have displayed 5-HT7 affinity in the nanomolar range. Among them, 1-(naphthyl)indole derivative 3p (Ki (5-HT7) = 4.5 nM) showed also a good selectivity over 5-HT1A, 5-HT2A and 5-HT6 receptors. This compound was pharmacology characterized as an antagonist.

  13. Cellular mechanisms of the 5-HT7 receptor-mediated signaling

    PubMed Central

    Guseva, Daria; Wirth, Alexander; Ponimaskin, Evgeni

    2014-01-01

    Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter regulating a wide range of physiological and pathological functions via activation of heterogeneously expressed 5-HT receptors. The 5-HT7 receptor is one of the most recently described members of the 5-HT receptor family. Functionally, 5-HT7 receptor is associated with a number of physiological and pathological responses, including serotonin-induced phase shifting of the circadian rhythm, control of memory as well as locomotor and exploratory activity. A large body of evidence indicates involvement of the 5-HT7 receptor in anxiety and depression, and recent studies suggest that 5-HT7 receptor can be highly relevant for the treatment of major depressive disorders. The 5-HT7 receptor is coupled to the stimulatory Gs-protein, and receptor stimulation results in activation of adenylyl cyclase (AC) leading to a rise of cAMP concentration. In addition, this receptor is coupled to the G12-protein to activate small GTPases of the Rho family. This review focuses on molecular mechanisms responsible for the 5-HT7 receptor-mediated signaling. We provide detailed overview of signaling cascades controlled and regulated by the 5-HT7 receptor and discuss the functional impact of 5-HT7 receptor for the regulation of different cellular and subcellular processes. PMID:25324743

  14. Blockade of 5-HT7 receptors reduces tactile allodynia in the rat.

    PubMed

    Amaya-Castellanos, Evelyn; Pineda-Farias, Jorge B; Castañeda-Corral, Gabriela; Vidal-Cantú, Guadalupe C; Murbartián, Janet; Rocha-González, Héctor I; Granados-Soto, Vinicio

    2011-10-01

    This study assessed the role of systemic and spinal 5-HT(7) receptors on rats submitted to spinal nerve injury. In addition, the 5-HT(7) receptors level in dorsal root ganglion and spinal cord was also determined. Tactile allodynia was induced by L5/L6 spinal nerve ligation. Systemic (0.01-10mg/kg) or spinal (0.3-30 μg) administration of the selective 5-HT(7) receptor antagonist SB-269970 but not vehicle reduced in a dose-dependent manner established tactile allodynia. This effect was maintained for about 6h. SB-269970 was more potent and effective by the spinal administration route than through systemic injection. Spinal nerve ligation reduced expression of 5-HT(7) receptors in the ipsilateral but not contralateral dorsal root ganglia. Moreover, 5-HT(7) receptor levels were lower in the ipsilateral dorsal spinal cord of neuropathic rats compared to naïve and sham rats. No changes in the receptor levels were observed in the contralateral dorsal spinal cord and in both regions of the ventral spinal cord. Data suggest that spinal 5-HT(7) receptors play a pronociceptive role in neuropathic rats. Results also indicate that spinal nerve injury leads to a reduced 5-HT(7) receptors level in pain processing-related areas which may result from its nociceptive role in this model. Data suggest that selective 5-HT(7) receptor antagonists may function as analgesics in nerve injury pain states.

  15. The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK.

    PubMed

    Lippiello, Pellegrino; Hoxha, Eriola; Speranza, Luisa; Volpicelli, Floriana; Ferraro, Angela; Leopoldo, Marcello; Lacivita, Enza; Perrone-Capano, Carla; Tempia, Filippo; Miniaci, Maria Concetta

    2016-02-01

    The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signaling mechanisms have never been described. Using patch-clamp recordings in cerebellar slices of adult mice, we investigated the effects of a selective 5-HT7R agonist, LP-211, on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that 5-HT7R activation induces long-term depression of parallel fiber-Purkinje cell synapse via a postsynaptic mechanism that involves the PKC-MAPK signaling pathway. Moreover, a 5-HT7R antagonist abolished the expression of PF-LTD, produced by pairing parallel fiber stimulation with Purkinje cell depolarization; whereas, application of a 5-HT7R agonist impaired LTP induced by 1 Hz parallel fiber stimulation. Our results indicate for the first time that 5-HT7R exerts a fine regulation of cerebellar bidirectional synaptic plasticity that might be involved in cognitive processes and neuropsychiatric disorders involving the cerebellum.

  16. Cellular mechanisms of the 5-HT7 receptor-mediated signaling.

    PubMed

    Guseva, Daria; Wirth, Alexander; Ponimaskin, Evgeni

    2014-01-01

    Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter regulating a wide range of physiological and pathological functions via activation of heterogeneously expressed 5-HT receptors. The 5-HT7 receptor is one of the most recently described members of the 5-HT receptor family. Functionally, 5-HT7 receptor is associated with a number of physiological and pathological responses, including serotonin-induced phase shifting of the circadian rhythm, control of memory as well as locomotor and exploratory activity. A large body of evidence indicates involvement of the 5-HT7 receptor in anxiety and depression, and recent studies suggest that 5-HT7 receptor can be highly relevant for the treatment of major depressive disorders. The 5-HT7 receptor is coupled to the stimulatory Gs-protein, and receptor stimulation results in activation of adenylyl cyclase (AC) leading to a rise of cAMP concentration. In addition, this receptor is coupled to the G12-protein to activate small GTPases of the Rho family. This review focuses on molecular mechanisms responsible for the 5-HT7 receptor-mediated signaling. We provide detailed overview of signaling cascades controlled and regulated by the 5-HT7 receptor and discuss the functional impact of 5-HT7 receptor for the regulation of different cellular and subcellular processes.

  17. The 5-HT7 receptor in learning and memory. Importance of the hippocampus

    PubMed Central

    Roberts, Amanda J.; Hedlund, Peter B.

    2011-01-01

    The 5-HT7 receptor is a more recently discovered G-protein-coupled receptor for serotonin. The functions and possible clinical relevance of this receptor are not yet fully understood. The present paper reviews to what extent the use of animal models of learning and memory and other techniques have implicated the 5-HT7 receptor in such processes. The studies have used a combination of pharmacological and genetic tools targeting the receptor to evaluate effects on behavior and cellular mechanisms. In tests such as the Barnes maze, contextual fear conditioning and novel location recognition that involve spatial learning and memory there is a considerable amount of evidence supporting an involvement of the 5-HT7 receptor. Supporting evidence has also been obtained in studies of mRNA expression and cellular signaling as well as in electrophysiological experiments. Especially interesting are the subtle but distinct effects observed in hippocampus-dependent models of place learning where impairments have been described in mice lacking the 5-HT7 receptor or after administration of a selective antagonist. While more work is required, it appears that 5-HT7 receptors are particularly important in allocentric representation processes. In instrumental learning tasks both procognitive effects and impairments in memory have been observed using pharmacological tools targeting the 5-HT7 receptor. In conclusion, the use of pharmacological and genetic tools in animal studies of learning and memory suggest a potentially important role for the 5-HT7 receptor in cognitive processes. PMID:21484935

  18. 5-HT7 receptor signaling: improved therapeutic strategy in gut disorders.

    PubMed

    Kim, Janice J; Khan, Waliul I

    2014-01-01

    Serotonin (5-hydroxytryptamine; 5-HT) is most commonly known for its role as a neurotransmitter in the central nervous system (CNS). However, the majority of the body's 5-HT is produced in the gut by enterochromaffin (EC) cells. Alterations in 5-HT signaling have been associated with various gut disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and enteric infections. Recently, our studies have identified a key role for 5-HT in the pathogenesis of experimental colitis. 5-HT7 receptors are expressed in the gut and very recently, we have shown evidence of 5-HT7 receptor expression on intestinal immune cells and demonstrated a key role for 5-HT7 receptors in generation of experimental colitis. This review summarizes the key findings of these studies and provides a comprehensive overview of our current knowledge of the 5-HT7 receptor in terms of its pathophysiological relevance and therapeutic potential in intestinal inflammatory conditions, such as IBD.

  19. The role of serotonin 5-HT7 receptor in regulating sleep and wakefulness.

    PubMed

    Monti, Jaime M; Jantos, Héctor

    2014-01-01

    Different approaches have been followed to characterize the role of 5-hydroxytryptamine (serotonin) receptor 7 (5-HT7) in the regulation of sleep-wake behavior: (1) 5-HT7 receptor knockout mice spend less time in rapid eye movement sleep than their wild-type counterparts, mainly during the light period. In contrast, there is no difference between the genotypes in time spent in wakefulness or slow-wave sleep. (2) Systemic administration of the selective 5-HT7 receptor agonist LP-211 significantly increased wakefulness (time spent awake) and reduced rapid eye movement sleep in the rat. Direct infusion of LP-211 into the dorsal raphe nucleus, locus coeruleus nucleus, basal forebrain (horizontal limb of the diagonal band of Broca), or laterodorsal tegmental nucleus also produced a decrease in rapid eye movement sleep. Additionally, microinjection of the 5-HT7 receptor agonist into the basal forebrain augmented the time animals remained awake. Local injection of the 5-HT7 receptor agonist LP-44 into the dorsal raphe nucleus also suppressed rapid eye movement sleep in the rat. (3) A similar reduction of rapid eye movement sleep has been described following intraperitoneal injection of the selective 5-HT7 receptor antagonists SB-269970 and SB-656104 in the rat and oral administration of the 5-HT7 receptor antagonist NJ-18038683 to rat and man. Local microinjection of SB-269970 into the dorsal raphe nucleus and basal forebrain also induced a decrease in rapid eye movement sleep in the rat. This tends to suggest that the on-off (activation/blockade), two-state ligand-receptor interaction model is not tenable for the 5-HT7 receptor.

  20. Spinal 5-HT7 receptors induce phrenic motor facilitation via EPAC-mTORC1 signaling

    PubMed Central

    Fields, D. P.; Springborn, S. R.

    2015-01-01

    Spinal serotonin type 7 (5-HT7) receptors elicit complex effects on motor activity. Whereas 5-HT7 receptor activation gives rise to long-lasting phrenic motor facilitation (pMF), it also constrains 5-HT2 receptor-induced pMF via “cross-talk inhibition.” We hypothesized that divergent cAMP-dependent signaling pathways give rise to these distinct 5-HT7 receptor actions. Specifically, we hypothesized that protein kinase A (PKA) mediates cross-talk inhibition of 5-HT2 receptor-induced pMF whereas 5-HT7 receptor-induced pMF results from exchange protein activated by cAMP (EPAC) signaling. Anesthetized, paralyzed, and ventilated rats receiving intrathecal (C4) 5-HT7 receptor agonist (AS-19) injections expressed pMF for >90 min, an effect abolished by pretreatment with a selective EPAC inhibitor (ESI-05) but not a selective PKA inhibitor (KT-5720). Furthermore, intrathecal injections of a selective EPAC activator (8-pCPT-2′-Me-cAMP) were sufficient to elicit pMF. Finally, spinal mammalian target of rapamycin complex-1 (mTORC1) inhibition via intrathecal rapamycin abolished 5-HT7 receptor- and EPAC-induced pMF, demonstrating that spinal 5-HT7 receptors elicit pMF by an EPAC-mTORC1 signaling pathway. Thus 5-HT7 receptors elicit and constrain spinal phrenic motor plasticity via distinct signaling mechanisms that diverge at cAMP (EPAC vs. PKA). Selective manipulation of these molecules may enable refined regulation of serotonin-dependent spinal motor plasticity for therapeutic advantage. PMID:26269554

  1. Spinal 5-HT7 receptors induce phrenic motor facilitation via EPAC-mTORC1 signaling.

    PubMed

    Fields, D P; Springborn, S R; Mitchell, G S

    2015-09-01

    Spinal serotonin type 7 (5-HT7) receptors elicit complex effects on motor activity. Whereas 5-HT7 receptor activation gives rise to long-lasting phrenic motor facilitation (pMF), it also constrains 5-HT2 receptor-induced pMF via "cross-talk inhibition." We hypothesized that divergent cAMP-dependent signaling pathways give rise to these distinct 5-HT7 receptor actions. Specifically, we hypothesized that protein kinase A (PKA) mediates cross-talk inhibition of 5-HT2 receptor-induced pMF whereas 5-HT7 receptor-induced pMF results from exchange protein activated by cAMP (EPAC) signaling. Anesthetized, paralyzed, and ventilated rats receiving intrathecal (C4) 5-HT7 receptor agonist (AS-19) injections expressed pMF for >90 min, an effect abolished by pretreatment with a selective EPAC inhibitor (ESI-05) but not a selective PKA inhibitor (KT-5720). Furthermore, intrathecal injections of a selective EPAC activator (8-pCPT-2'-Me-cAMP) were sufficient to elicit pMF. Finally, spinal mammalian target of rapamycin complex-1 (mTORC1) inhibition via intrathecal rapamycin abolished 5-HT7 receptor- and EPAC-induced pMF, demonstrating that spinal 5-HT7 receptors elicit pMF by an EPAC-mTORC1 signaling pathway. Thus 5-HT7 receptors elicit and constrain spinal phrenic motor plasticity via distinct signaling mechanisms that diverge at cAMP (EPAC vs. PKA). Selective manipulation of these molecules may enable refined regulation of serotonin-dependent spinal motor plasticity for therapeutic advantage.

  2. Effects of the potential 5-HT7 receptor agonist AS 19 in an autoshaping learning task.

    PubMed

    Perez-García, Georgina S; Meneses, A

    2005-08-30

    This work aimed to evaluate further the role of 5-HT7 receptors during memory formation in an autoshaping Pavlovian/instrumental learning task. Post-training administration of the potential 5-HT7 receptor agonist AS 19 or antagonist SB-269970 enhanced memory formation or had no effect, respectively. The AS 19 facilitatory effect was reversed by SB-269970, but not by the selective 5-HT1A antagonist WAY100635. Amnesia induced by scopolamine (cholinergic antagonist) or dizocilpine (NMDA antagonist) was also reversed by AS 19. Certainly, reservations regarding the selectivity of AS 19 for 5-HT7 and other 5-HT receptors in vivo are noteworthy and, therefore, its validity for use in animal models as a pharmacological tool. Having mentioned that, it should be noticed that together these data are providing further support to the notion of the 5-HT7 receptors role in memory formation. Importantly, this 5-HT7 receptor agonist AS 19 appears to represent a step forward respect to the notion that potent and selective 5-HT7 receptor agonists can be useful in the treatment of dysfunctional memory in aged-related decline and Alzheimer's disease.

  3. Activation of 5-HT7 receptors increases neuronal platelet-derived growth factor β receptor expression.

    PubMed

    Vasefi, Maryam S; Kruk, Jeff S; Liu, Hui; Heikkila, John J; Beazely, Michael A

    2012-03-09

    Several antipsychotics have a high affinity for 5-HT7 receptors yet despite intense interest in the 5-HT7 receptor as a potential drug target to treat psychosis, the function and signaling properties of 5-HT7 receptors in neurons remain largely uncharacterized. In primary mouse hippocampal and cortical neurons, as well as in the SH-SY5Y cell line, incubation with 5-HT, 5-carboxamidotryptamine (5-CT), or 5-HT7 receptor-selective agonists increases the expression of platelet-derived growth factor (PDGF)β receptors. The increased PDGFβ receptor expression is cyclic AMP-dependent protein kinase (PKA)-dependent, suggesting that 5-HT7 receptors couple to Gα(s) in primary neurons. Interestingly, up-regulated PDGFβ receptors display an increased basal phosphorylation state at the phospholipase Cγ-activating tyrosine 1021. This novel linkage between the 5-HT7 receptor and the PDGF system may be an important GPCR-neurotrophic factor signaling pathway in neurons.

  4. 5-HT7 receptor modulators: Amino groups attached to biphenyl scaffold determine functional activity.

    PubMed

    Kim, Youngjae; Park, Hyeri; Lee, Jeongeun; Tae, Jinsung; Kim, Hak Joong; Min, Sun-Joon; Rhim, Hyewhon; Choo, Hyunah

    2016-11-10

    5-HT7 receptor (5-HT7R) agonists and antagonists have been reported to be used for treatment of neuropathic pain and depression, respectively. In this study, as a novel scaffold for 5-HT7R modulators, we designed and prepared a series of biphenyl-3-yl-methanamine derivatives with various amino groups. Evaluation of functional activities as well as binding affinities of the title compounds identified partial agonists (EC50 = 0.55-3.2 μM) and full antagonists (IC50 = 5.57-23.1 μM) depending on the amino substituents. Molecular docking study suggested that the ligand-based switch in functional activity from agonist to antagonist results from the size of the amino groups and thereby different binding modes to 5-HT7R. In particular, interaction of the ligand with Arg367 of 5-HT7R is shown to differentiate agonists and antagonists. In the pharmacophore model study, two distinct pharmacophore models can tell whether a ligand is an agonist or an antagonist. Taken together, this study provides valuable information for designing novel compounds with selective agonistic or antagonistic properties against 5-HT7R.

  5. [5-HT1A/5-HT7 receptor interplay: Chronic activation of 5-HT7 receptors decreases the functional activity of 5-HT1A receptor and its сontent in the mouse brain].

    PubMed

    Kondaurova, E M; Bazovkina, D V; Naumenko, V S

    2017-01-01

    Serotonin receptors 5-HT1A and 5-HT7 are involved in the development of various psychopathologies. Some data indicate that there is an interplay between 5-HT1A 5-HT7 receptors that could be implicated in the regulation of their function. This work analyzed the effects of chronic 5-HT7 activation on the functional activity of 5-HT7 and 5-HT1A receptors, on the corresponding protein levels, and on the expression of genes encoding 5-HT7 and 5-HT1A receptors in the mouse brain. Chronic administration of the 5-HT7 selective agonist LP44 (20.5 nmol, i.c.v., 14 days) produced considerable desensitization of both 5-HT7 and 5-HT1A receptors. In LP44-treated mice, the hypothermic responses mediated by both 5-HT7 and 5-HT1A receptors were attenuated. Moreover, the levels of 5-HT1A receptor protein in the midbrain and the frontal cortex of LP44-treated mice were significantly decreased. However, the brain levels of 5-HT7 receptor protein did not differ between LP44-treated and control mice. Chronic LP44 treatment did not alter the expression of the 5-HT7 and 5-HT1A receptor genes in all investigated brain structure. These data suggest that 5-HT7 receptors participate in the posttranscriptional regulation of the 5-HT1A receptors functioning.

  6. Functional expression of the serotonin 5-HT7 receptor in human glioblastoma cell lines

    PubMed Central

    Mahé, Cécile; Bernhard, Michel; Bobirnac, Ionel; Keser, Corinna; Loetscher, Erika; Feuerbach, Dominik; Dev, Kumlesh K; Schoeffter, Philippe

    2004-01-01

    Serotonin 5-HT7 receptors are present in astrocytes. Understanding their role in this type of cell would greatly benefit from the identification of astroglial cell lines expressing this receptor type. The aim of the present study was to assess the expression of native 5-HT7 receptors and 5-HT7 receptor mRNA in a number of human glioblastoma cell lines, by means of cAMP measurements, Western blot analysis and reverse transcriptase–polymerase chain reaction (RT–PCR) analysis. 5-Hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), 5-methoxytryptamine (5-MeOT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induced concentration-dependent stimulations of cAMP accumulation in the human glioblastoma cell lines, U-373 MG, U-138 MG, U-87 MG, DBTRG-05MG, T98G, H4, CCF-STTG1 and Hs 683. The rank order of potency was 5-CT>5-HT=5-MeOT≫8-OH-DPAT. The effect of 5-CT was inhibited in a concentration-dependent manner by the selective 5-HT7 receptor antagonist SB-269970 in all human glioblastoma cells. Schild analyses yielded slope factors close to unity (0.89–1.13) and pA2 values of 8.69–9.05. Western blot analysis revealed the presence of immunoreactive bands corresponding to the human 5-HT7 receptor in extracts of all human glioblastoma cell lines. The presence of the three splice variants of the 5-HT7 receptor (5-HT7(a/b/d)) was visualized by RT–PCR analysis with specific primers in all human glioblastoma cell lines. In conclusion, human glioblastoma cell lines express functional 5-HT7 receptors and the three splice variants of the corresponding mRNA. These cell lines could serve as model systems of native 5-HT7 receptors in glial cells to investigate their putative role in processes like release of neurotrophic factors or inflammatory cytokines. PMID:15339860

  7. [Study on specificity of acupuncture effect of Shenmen (HT 7) and Daling (PC 7)].

    PubMed

    Li, Zhen-Jing; Sun, Zhong-Ren; Sun, Chen-Yi; Tong, Xin

    2012-04-01

    To observe the effect of acupunture at Shenmen (HT 7) and Daling (PC 7) on different cerebral functional regions by Functional Magnetic Resonance Imaging (MRI), and discuss the relative specificity of effect of these two acupoints. Ten healthy right-handed volunteers were enrolled in this research. Under the scan of fMRI with the pattern of "rest-stimulation-rest-stimulation-rest", acupuncture stimulation was given at Shenmen (HT 7) and Daling (PC 7) on the right side, and all the data were analyzed with Matlab software and SPM5 package to observe the activated cerebral regions. The activated brodmann areas by acupuncture at Shenmen (HT 7) were mainly BA10 BA13, BA47, BA22 on the left side and BA40 BA44 on the right side, while the activated areas by acupunoture at Daling (PC7) were BA46, BA47, BA22 BA10. BA45 on the left side and BA44 BA9, BA6. BA40 on the right side. The activated cerebral functional regions of acupuncture stimulation at Shenmen (HT 7) and Daling (PC 7) are not exactly the same, which indicates that the acupuncture effects of the two acupoints are specific. With the same activated areas of language and cognitive function, the Shenmen (HT 7) specializes in emotion control while the Daling (PC 7) could active the autonomic nerve function area.

  8. Improvement of ketamine-induced social withdrawal in rats: the role of 5-HT7 receptors.

    PubMed

    Hołuj, Małgorzata; Popik, Piotr; Nikiforuk, Agnieszka

    2015-12-01

    Social withdrawal, one of the core negative symptoms of schizophrenia, can be modelled in the social interaction (SI) test in rats using N-methyl-D-aspartate receptor glutamate receptor antagonists. We have recently shown that amisulpride, an antipsychotic with a high affinity for serotonin 5-HT7 receptors, reversed ketamine-induced SI deficits in rats. The aim of the present study was to further elucidate the potential involvement of 5-HT7 receptors in the prosocial action of amisulpride. Acute administration of amisulpride (3 mg/kg) and SB-269970 (1 mg/kg), a 5-HT7 receptor antagonist, reversed ketamine-induced social withdrawal, whereas sulpiride (20 or 30 mg/kg) and haloperidol (0.2 mg/kg) were ineffective. The 5-HT7 receptor agonist AS19 (10 mg/kg) abolished the prosocial efficacy of amisulpride (3 mg/kg). The coadministration of an inactive dose of SB-269970 (0.2 mg/kg) showed the prosocial effects of inactive doses of amisulpride (1 mg/kg) and sulpiride (20 mg/kg). The anxiolytic chlordiazepoxide (2.5 mg/kg) and the antidepressant fluoxetine (2.5 mg/kg) were ineffective in reversing ketamine-induced SI deficits. The present study suggests that the antagonism of 5-HT7 receptors may contribute towards the mechanisms underlying the prosocial action of amisulpride. These results may have therapeutic implications for the treatment of negative symptoms in schizophrenia and other disorders characterized by social withdrawal.

  9. Amisulpride promotes cognitive flexibility in rats: the role of 5-HT7 receptors.

    PubMed

    Nikiforuk, Agnieszka; Popik, Piotr

    2013-07-01

    The antagonism of 5-HT7 receptors may contribute to the antidepressant and procognitive actions of the atypical antipsychotic drug, amisulpride. It has been previously demonstrated that the selective 5-HT7 receptor antagonist reversed restraint stress-induced cognitive impairments in a rat model of frontal-dependent attentional set-shifting task (ASST). Therefore, the first aim of the present study was to assess the effectiveness of amisulpride against stress-evoked cognitive inflexibility. The second goal was to elucidate whether the pro-cognitive effect of amisulpride could be due to the compound's action at 5-HT7 receptors. Rats repeatedly exposed (1 h daily for 7 days) to restraint stress demonstrated impaired performance on the extra-dimensional (ED) set-shifting stage of the ASST. Amisulpride (3 mg/kg) given to stressed rats 30 min before testing reversed this restraint-induced cognitive inflexibility and improved ED performance of the unstressed control group. The 5-HT7 receptor agonist, AS19 (10 mg/kg), abolished the pro-cognitive efficacy of amisulpride (3 mg/kg). The present study suggests that the antagonism of 5-HT7 receptors may contribute to the mechanisms underlining the pro-cognitive action of amisulpride. These results may have therapeutic implications in frontal-like deficits associated with stress-related disorders.

  10. Assessment of 5-HT7 Receptor Agonists Selectivity Using Nociceptive and Thermoregulation Tests in Knockout versus Wild-Type Mice

    PubMed Central

    Brenchat, Alex; Rocasalbas, Maria; Zamanillo, Daniel; Hamon, Michel; Vela, José Miguel; Romero, Luz

    2012-01-01

    No study has ever examined the effect of 5-HT7 receptor agonists on nociception by using 5-HT7 receptor knockout mice. Basal sensitivity to noxious heat stimuli and formalin-induced nociception in both phase I and II of the formalin test did not differ in 5-HT7 receptor knockout mice and paired wild-type controls. Similarly, there was no significant difference in basal body temperature between both genotypes. Subcutaneous administration of 5-HT7 receptor agonists AS-19 (10 mg/kg), E-57431 (10 mg/kg), and E-55888 (20 mg/kg) significantly reduced formalin-induced licking/biting behavior during the phase II of the test in wild-type but not in 5-HT7 receptor knockout mice. At these active analgesic doses, none of the three 5-HT7 receptor agonists modified the basal body temperature neither in wild-type nor in 5-HT7 receptor knockout mice. However, a significant decrease in body temperature was observed at a higher dose (20 mg/kg) of AS-19 and E-57431 in both genotypes. Our data strongly suggest that the 5-HT7 receptor agonists AS-19, E-57431, and E-55888 produce antinociception in the formalin test by activating 5-HT7 receptors. These results also strengthen the idea that the 5-HT7 receptor plays a role in thermoregulation, but by acting in concert with other receptors. PMID:22761612

  11. Design and synthesis of dual 5-HT1A and 5-HT7 receptor ligands.

    PubMed

    Ofori, Edward; Zhu, Xue Y; Etukala, Jagan R; Peprah, Kwakye; Jordan, Kamanski R; Adkins, Adia A; Bricker, Barbara A; Kang, Hye J; Huang, Xi-Ping; Roth, Bryan L; Ablordeppey, Seth Y

    2016-08-15

    5-HT1A and 5-HT7 receptors have been at the center of discussions recently due in part to their major role in the etiology of major central nervous system diseases such as depression, sleep disorders, and schizophrenia. As part of our search to identify dual targeting ligands for these receptors, we have carried out a systematic modification of a selective 5HT7 receptor ligand culminating in the identification of several dual 5-HT1A and 5-HT7 receptor ligands. Compound 16, a butyrophenone derivative of tetrahydroisoquinoline (THIQ), was identified as the most potent agent with low nanomolar binding affinities to both receptors. Interestingly, compound 16 also displayed moderate affinity to other clinically relevant dopamine receptors. Thus, it is anticipated that compound 16 may serve as a lead for further exploitation in our quest to identify new ligands with the potential to treat diseases of CNS origin.

  12. SB-656104-A, a novel selective 5-HT7 receptor antagonist, modulates REM sleep in rats.

    PubMed

    Thomas, David R; Melotto, Sergio; Massagrande, Mario; Gribble, Andrew D; Jeffrey, Phillip; Stevens, Alexander J; Deeks, Nigel J; Eddershaw, Peter J; Fenwick, Susan H; Riley, Graham; Stean, Tania; Scott, Claire M; Hill, Matthew J; Middlemiss, Derek N; Hagan, Jim J; Price, Gary W; Forbes, Ian T

    2003-06-01

    1 (6-((R)-2-[2-[4-(4-Chloro-phenoxy)-piperidin-1-yl]-ethyl]-pyrrolidine-1-sulphonyl)-1H-indole hydrochloride) (SB-656104-A), a novel 5-hydroxytryptamine (5-HT(7)) receptor antagonist, potently inhibited [(3)H]-SB-269970 binding to the human cloned 5-HT(7(a)) (pK(i) 8.7+/-0.1) and 5-HT(7(b)) (pK(i) 8.5+/-0.2) receptor variants and the rat native receptor (pK(i) 8.8+/-0.2). The compound displayed at least 30-fold selectivity for the human 5-HT(7(a)) receptor versus other human cloned 5-HT receptors apart from the 5-HT(1D) receptor ( approximately 10-fold selective). 2 SB-656104-A antagonised competitively the 5-carboxamidotryptamine (5-CT)-induced accumulation of cyclic AMP in h5-HT(7(a))/HEK293 cells with a pA(2) of 8.5. 3 Following a constant rate iv infusion to steady state in rats, SB-656104 had a blood clearance (CL(b)) of 58+/-6 ml min(-1) kg(-1) and was CNS penetrant with a steady-state brain : blood ratio of 0.9 : 1. Following i.p. administration to rats (10 mg kg(-1)), the compound displayed a t(1/2) of 1.4 h with mean brain and blood concentrations (at 1 h after dosing) of 0.80 and 1.0 micro M, respectively. 4 SB-656104-A produced a significant reversal of the 5-CT-induced hypothermic effect in guinea pigs, a pharmacodynamic model of 5-HT(7) receptor interaction in vivo (ED(50) 2 mg kg(-1)). 5 SB-656104-A, administered to rats at the beginning of the sleep period (CT 0), significantly increased the latency to onset of rapid eye movement (REM) sleep at 30 mg kg(-1) i.p. (+93%) and reduced the total amount of REM sleep at 10 and 30 mg kg(-1) i.p. with no significant effect on the latency to, or amount of, non-REM sleep. SB-269970-A produced qualitatively similar effects in the same study. 6 In summary, SB-656104-A is a novel 5-HT(7) receptor antagonist which has been utilised in the present study to provide further evidence for a role for 5-HT(7) receptors in the modulation of REM sleep.

  13. Molecular imaging of the serotonin 5-HT7 receptors: from autoradiography to positron emission tomography.

    PubMed

    Zimmer, Luc; Billard, Thierry

    2014-01-01

    Serotonin and its various receptors are involved in numerous brain functions and neuropsychiatric disorders. Of the 14 known serotoninergic receptors, the 5-HT7 receptor is the most recently identified and characterized. It is closely involved in the pathogenesis of depression, anxiety, epilepsy and pain and is therefore an important target for drug therapy. It is a crucial target in neuroscience, and there is a clear need for radioligands for in vitro and in vivo visualization and quantification, first in animal models and ultimately in humans. This review focuses on the main radioligands suggested for in vitro and in vivo imaging of the 5-HT7 receptor.

  14. Pharmacological Blockade of 5-HT7 Receptors as a Putative Fast Acting Antidepressant Strategy

    PubMed Central

    Mnie-Filali, Ouissame; Faure, Céline; Lambás-Señas, Laura; Mansari, Mostafa El; Belblidia, Hassina; Gondard, Elise; Etiévant, Adeline; Scarna, Hélène; Didier, Anne; Berod, Anne; Blier, Pierre; Haddjeri, Nasser

    2011-01-01

    Current antidepressants still display unsatisfactory efficacy and a delayed onset of therapeutic action. Here we show that the pharmacological blockade of serotonin 7 (5-HT7) receptors produced a faster antidepressant-like response than the commonly prescribed antidepressant fluoxetine. In the rat, the selective 5-HT7 receptor antagonist SB-269970 counteracted the anxiogenic-like effect of fluoxetine in the open field and exerted an antidepressant-like effect in the forced swim test. In vivo, 5-HT7 receptors negatively regulate the firing activity of dorsal raphe 5-HT neurons and become desensitized after long-term administration of fluoxetine. In contrast with fluoxetine, a 1-week treatment with SB-269970 did not alter 5-HT firing activity but desensitized cell body 5-HT autoreceptors, enhanced the hippocampal cell proliferation, and counteracted the depressive-like behavior in olfactory bulbectomized rats. Finally, unlike fluoxetine, early-life administration of SB-269970, did not induce anxious/depressive-like behaviors in adulthood. Together, these findings indicate that the 5-HT7 receptor antagonists may represent a new class of antidepressants with faster therapeutic action. PMID:21326194

  15. Raman calibration of the HT-7 yttrium aluminum garnet Thomson scattering for electron density measurements

    SciTech Connect

    Zang Qing; Zhao Junyu; Gao Xiang; Shi Lingwei; Zhang Tao; Xi Xiaoqi; Yang Li; Hu Qingsheng; Sajjad, S.

    2007-11-15

    A multipulse neodym doped yttrium aluminum garnet laser Thomson scattering system calibrated by the anti-Stokes rotational Raman scattering from nitrogen gas had been developed in the HT-7 superconducting Tokmak. By virtue of this system, measured electron density results of the plasma were obtained. The results showed good repeatability and its total uncertainty was estimated to be {+-}18%.

  16. Memory formation and memory alterations: 5-HT6 and 5-HT7 receptors, novel alternative.

    PubMed

    Meneses, Alfredo

    2014-01-01

    Agonists and antagonists of the 5-hydroxytryptamine (serotonin) receptor6 (5-HT6) or receptor7 (5-HT7) might improve memory and/or reverse amnesia, although the mechanisms involved are poorly understood. Hence, the current work summarizes recent reviews and findings involving these receptors. Evidence indicates that diverse 5-HT6 receptor antagonists produce promnesic and/or antiamnesic effect in conditions, such as memory formation, age-related cognitive impairments and memory deficit in preclinical studies, as well as in diseases such as schizophrenia, Parkinson's, and Alzheimer's disease (AD). Memory, aging, and AD modify 5-HT6 receptors and signaling cascades; likewise, the modulation of 5-HT6 drugs on memory seems to be accompanied with neural changes. Moreover, 5-HT7 receptors are localized in brain areas mediating memory, including the cortex, hippocampus (e.g., Zola-Morgan and Squire, 1993) and raphe nuclei; however, the role of these receptors on memory has yet to be fully explored. Hence, findings and reviews are summarized in this work. Evidence suggests that both 5-HT7 receptor agonists and antagonists might have promnesic and anti-amnesic effects. These effects seem to be dependent on the basal level of performance, i.e., normal or impaired. Available evidence suggests that a potential utility of 5-HT6 and 5-HT7 receptor in mild-to-moderate AD patients and other memory dysfunctions as therapeutic targets.

  17. Spatial memory deficit across aging: current insights of the role of 5-HT7 receptors

    PubMed Central

    Beaudet, Gregory; Bouet, Valentine; Jozet-Alves, Christelle; Schumann-Bard, Pascale; Dauphin, François; Paizanis, Eleni; Boulouard, Michel; Freret, Thomas

    2015-01-01

    Elderly persons often face biological, psychological or social changes over time that may cause discomfort or morbidity. While some cognitive domains remain stable over time, others undergo a decline. Spatial navigation is a complex cognitive function essential for independence, safety and quality of life. While egocentric (body-centered) navigation is quite preserved during aging, allocentric (externally-centered) navigation—based on a cognitive map using distant landmarks—declines with age. Recent preclinical studies showed that serotonergic 5-HT7 receptors are localized in brain regions associated with allocentric spatial navigation processing. Behavioral assessments with pharmacological or genetic tools have confirmed the role of 5-HT7 receptors in allocentric navigation. Moreover, few data suggested a selective age-related decrease in the expression of 5-HT7 receptors in pivotal brain structures implicated in allocentric navigation such as the hippocampal CA3 region. We aim to provide a short overview of the potential role of 5-HT7 receptors in spatial navigation, and to argue for their interests as therapeutic targets against age-related cognitive decline. PMID:25642173

  18. 3D QSAR based design of novel oxindole derivative as 5HT7 inhibitors.

    PubMed

    Chitta, Aparna; Sivan, Sree Kanth; Manga, Vijjulatha

    2014-06-01

    To understand the structural requirements of 5-hydroxytryptamine (5HT7) receptor inhibitors and to design new ligands against 5HT7 receptor with enhanced inhibitory potency, a three-dimensional quantitative structure-activity relationship study with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a data set of 56 molecules consisting of oxindole, tetrahydronaphthalene, aryl ketone substituted arylpiperazinealkylamide derivatives was performed. Derived model showed good statistical reliability in terms of predicting 5HT7 inhibitory activity of the molecules, based on molecular property fields like steric, electrostatic, hydrophobic, hydrogen bond donor and hydrogen bond acceptor fields. This is evident from statistical parameters like conventional r2 and a cross validated (q2) values of 0.985, 0.743 for CoMFA and 0.970, 0.608 for CoMSIA, respectively. Predictive ability of the models to determine 5HT7 antagonistic activity is validated using a test set of 16 molecules that were not included in the training set. Predictive r2 obtained for the test set was 0.560 and 0.619 for CoMFA and CoMSIA, respectively. Steric, electrostatic fields majorly contributed toward activity which forms the basis for design of new molecules. Absorption, distribution, metabolism and elimination (ADME) calculation using QikProp 2.5 (Schrodinger 2010, Portland, OR) reveals that the molecules confer to Lipinski's rule of five in majority of the cases.

  19. 5-HT7 receptor signaling: improved therapeutic strategy in gut disorders

    PubMed Central

    Kim, Janice J.; Khan, Waliul I.

    2014-01-01

    Serotonin (5-hydroxytryptamine; 5-HT) is most commonly known for its role as a neurotransmitter in the central nervous system (CNS). However, the majority of the body’s 5-HT is produced in the gut by enterochromaffin (EC) cells. Alterations in 5-HT signaling have been associated with various gut disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and enteric infections. Recently, our studies have identified a key role for 5-HT in the pathogenesis of experimental colitis. 5-HT7 receptors are expressed in the gut and very recently, we have shown evidence of 5-HT7 receptor expression on intestinal immune cells and demonstrated a key role for 5-HT7 receptors in generation of experimental colitis. This review summarizes the key findings of these studies and provides a comprehensive overview of our current knowledge of the 5-HT7 receptor in terms of its pathophysiological relevance and therapeutic potential in intestinal inflammatory conditions, such as IBD. PMID:25565996

  20. Spatial memory deficit across aging: current insights of the role of 5-HT7 receptors.

    PubMed

    Beaudet, Gregory; Bouet, Valentine; Jozet-Alves, Christelle; Schumann-Bard, Pascale; Dauphin, François; Paizanis, Eleni; Boulouard, Michel; Freret, Thomas

    2014-01-01

    Elderly persons often face biological, psychological or social changes over time that may cause discomfort or morbidity. While some cognitive domains remain stable over time, others undergo a decline. Spatial navigation is a complex cognitive function essential for independence, safety and quality of life. While egocentric (body-centered) navigation is quite preserved during aging, allocentric (externally-centered) navigation-based on a cognitive map using distant landmarks-declines with age. Recent preclinical studies showed that serotonergic 5-HT7 receptors are localized in brain regions associated with allocentric spatial navigation processing. Behavioral assessments with pharmacological or genetic tools have confirmed the role of 5-HT7 receptors in allocentric navigation. Moreover, few data suggested a selective age-related decrease in the expression of 5-HT7 receptors in pivotal brain structures implicated in allocentric navigation such as the hippocampal CA3 region. We aim to provide a short overview of the potential role of 5-HT7 receptors in spatial navigation, and to argue for their interests as therapeutic targets against age-related cognitive decline.

  1. Memory time-course: mRNA 5-HT1A and 5-HT7 receptors.

    PubMed

    Perez-Garcia, Georgina; Meneses, Alfredo

    2009-08-24

    In an attempt to clarify conflicting results about serotonin (5-hydroxytryptamine, 5-HT) 5-HT(1A) and 5-HT(7) receptors in memory formation, their mRNA expression was determined by RT-PCR in key brain areas for explicit and implicit memory. The time-course (0-120 h) of autoshaped responses was progressive and mRNA 5-HT(1A) or 5-HT(7) receptors expression monotonically augmented or declined in prefrontal cortex, hippocampus and raphe nuclei, respectively. At 24-48 h acutely 8-OH-DPAT (0.062 mg/kg) administration enhanced memory and attenuated mRNA 5-HT(1A)<5-HT(7) receptors expression respect to saline group. WAY100635 (0.3 mg/kg) or SB-269970 (10.0 mg/kg) did not affect the former, partially blocked or reversed the latter, respectively. Furthermore, lower WAY100635 (0.001-0.1 mg/kg) or SB-269970 (1.0-5.0 mg/kg) doses plus 8-OHDPAT not affected memory; however both combinations suppressed or up-regulated mRNA expression 5-HT(1A) or 5-HT(7) receptors. In contrast, AS19 (5.0 mg/kg) facilitated memory consolidation, decreased or increased hippocampal 5-HT(7) and 5-HT(1A) receptors expression. Together these data revealed that, when both 5-HT(1A) and 5-HT(7) receptors were stimulated by 8-OHDPAT under memory consolidation, subtle changes emerged, not evident at behavioral level though detectable at genes expression. Notably, high levels of efficient memory were maintained even when serotonergic tone, via either 5-HT(1A) or 5-HT(7) receptor, was down- or up-regulated. Nevertheless, WAY100635 plus SB-269970 impaired memory consolidation and suppressed their expression. Considering that serotonergic changes are prominent in AD patients with an earlier onset of disease the present approach might be useful in the identification of functional changes associated to memory formation, memory deficits and reversing or even preventing these deficits.

  2. 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation

    PubMed Central

    Samarajeewa, Anshula; Goldemann, Lolita; Vasefi, Maryam S.; Ahmed, Nawaz; Gondora, Nyasha; Khanderia, Chandni; Mielke, John G.; Beazely, Michael A.

    2014-01-01

    The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the cortex and hippocampus. We have previously demonstrated that the application of 5-HT7 receptor agonists to primary hippocampal neurons and SH-SY5Y cells increases platelet-derived growth factor (PDGF) receptor expression and promotes neuroprotection against N-methyl-D-aspartate-(NMDA)-induced toxicity. The tropomyosin-related kinase B (TrkB) receptor is one of the receptors for brain-derived neurotrophic factor (BDNF) and is associated with neurodevelopmental and neuroprotective effects. Application of LP 12 to primary cerebral cortical cultures, SH-SY5Y cells, as well as the retinal ganglion cell line, RGC-5, increased both the expression of full length TrkB as well as its basal phosphorylation state at tyrosine 816. The increase in TrkB expression and phosphorylation was observed as early as 30 min after 5-HT7 receptor activation. In addition to full-length TrkB, kinase domain-deficient forms may be expressed and act as dominant-negative proteins toward the full length receptor. We have identified distinct patterns of TrkB isoform expression across our cell lines and cortical cultures. Although TrkB receptor expression is regulated by cyclic AMP and Gαs-coupled GPCRs in several systems, we demonstrate that, depending on the model system, pathways downstream of both Gαs and Gα12 are involved in the regulation of TrkB expression by 5-HT7 receptors. Given the number of psychiatric and degenerative diseases associated with TrkB/BDNF deficiency and the current interest in developing 5-HT7 receptor ligands as pharmaceuticals, identifying signaling relationships between these two receptors will aid in our understanding of the potential therapeutic effects of 5-HT7 receptor ligands. PMID:25426041

  3. Signalling properties and pharmacology of a 5-HT7 -type serotonin receptor from Tribolium castaneum.

    PubMed

    Vleugels, R; Lenaerts, C; Vanden Broeck, J; Verlinden, H

    2014-04-01

    In the last decade, genome sequence data and gene structure information on invertebrate receptors has been greatly expanded by large sequencing projects and cloning studies. This information is of great value for the identification of receptors; however, functional and pharmacological data are necessary for an accurate receptor classification and for practical applications. In insects, an important group of neurotransmitter and neurohormone receptors, for which ample sequence information is available but pharmacological information is missing, are the biogenic amine G protein-coupled receptors (GPCRs). In the present study, we investigated the sequence information, pharmacology and signalling properties of a 5-HT7 -type serotonin receptor from the red flour beetle, Tribolium castaneum (Trica5-HT7 ). The receptor encoding cDNA shows considerable sequence similarity with cognate 5-HT7 receptors and phylogenetic analysis also clusters the receptor within this 5-HT receptor group. Real-time reverse transcription PCR demonstrated high expression levels in the brain, indicating the possible importance of this receptor in neural processes. Trica5-HT7 was dose-dependently activated by 5-HT, which induced elevated intracellular cyclic AMP levels but had no effect on calcium signalling. The synthetic agonists, α-methyl 5-HT, 5-methoxytryptamine, 5-carboxamidotryptamine and 8-hydroxy-2-(dipropylamino)tetralin hydrobromide, showed a response, although with a much lower potency and efficacy than 5-HT. Ketanserin and methiothepin were the most potent antagonists. Both showed characteristics of competitive inhibition on Trica5-HT7 . The signalling pathway and pharmacological profile offer important information that will facilitate functional and comparative studies of 5-HT receptors in insects and other invertebrates. The pharmacology of invertebrate 5-HT receptors differs considerably from that of vertebrates. The present study may therefore contribute to establishing a more

  4. 5-HT1A and 5-HT7 receptors contribute to lurasidone-induced dopamine efflux.

    PubMed

    Huang, Mei; Horiguchi, Masakuni; Felix, Anna R; Meltzer, Herbert Y

    2012-05-09

    Lurasidone is a novel, atypical antipsychotic drug with serotonin [5-hydroxytryptamine (5-HT)]2A, 5-HT7, dopamine (DA) D2 antagonist, and 5-HT1A receptor partial agonist properties. The ability of lurasidone to reverse the effects of subchronic administration phencyclidine, to impair novel object recognition in rats, an animal model of cognitive impairment in schizophrenia, is dependent, in part, on its 5-HT1A agonist and 5-HT7 receptor antagonist properties. We tested whether 5-HT1A partial agonism or 5-HT7 antagonism, or both, contributed to the ability of lurasidone to enhance cortical and hippocampal DA efflux, which may be related to its ability to improve cognition. Here, we report that lurasidone, 0.25 and 0.5, but not 0.1 mg/kg, subcutaneously, significantly increased DA efflux in the prefrontal cortex and hippocampus in a dose-dependent manner. Lurasidone, 0.5 mg/kg, also produced a smaller increase in DA efflux in the nucleus accumbens. Pretreatment with the 5-HT1A receptor antagonist, WAY100635 (0.2 mg/kg, subcutaneously), partially blocked the lurasidone-induced cortical and hippocampal DA efflux. Further, subeffective doses of the 5-HT1A receptor agonist, tandospirone (0.2 mg/kg), or the 5-HT7 antagonist, SB269970 (0.3 mg/kg), potentiated the ability of a subeffective dose of lurasidone (0.1 mg/kg) to increase DA efflux in the prefrontal cortex. These findings suggest that the effects of lurasidone on the prefrontal cortex and hippocampus, DA efflux are dependent, at least partially, on its 5-HT1A agonist and 5-HT7 antagonist properties and may contribute to its efficacy to reverse the effects of subchronic phencyclidine treatment and improve schizophrenia.

  5. 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation.

    PubMed

    Samarajeewa, Anshula; Goldemann, Lolita; Vasefi, Maryam S; Ahmed, Nawaz; Gondora, Nyasha; Khanderia, Chandni; Mielke, John G; Beazely, Michael A

    2014-01-01

    The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the cortex and hippocampus. We have previously demonstrated that the application of 5-HT7 receptor agonists to primary hippocampal neurons and SH-SY5Y cells increases platelet-derived growth factor (PDGF) receptor expression and promotes neuroprotection against N-methyl-D-aspartate-(NMDA)-induced toxicity. The tropomyosin-related kinase B (TrkB) receptor is one of the receptors for brain-derived neurotrophic factor (BDNF) and is associated with neurodevelopmental and neuroprotective effects. Application of LP 12 to primary cerebral cortical cultures, SH-SY5Y cells, as well as the retinal ganglion cell line, RGC-5, increased both the expression of full length TrkB as well as its basal phosphorylation state at tyrosine 816. The increase in TrkB expression and phosphorylation was observed as early as 30 min after 5-HT7 receptor activation. In addition to full-length TrkB, kinase domain-deficient forms may be expressed and act as dominant-negative proteins toward the full length receptor. We have identified distinct patterns of TrkB isoform expression across our cell lines and cortical cultures. Although TrkB receptor expression is regulated by cyclic AMP and Gαs-coupled GPCRs in several systems, we demonstrate that, depending on the model system, pathways downstream of both Gαs and Gα12 are involved in the regulation of TrkB expression by 5-HT7 receptors. Given the number of psychiatric and degenerative diseases associated with TrkB/BDNF deficiency and the current interest in developing 5-HT7 receptor ligands as pharmaceuticals, identifying signaling relationships between these two receptors will aid in our understanding of the potential therapeutic effects of 5-HT7 receptor ligands.

  6. Serotonin 5-HT7 receptor increases the density of dendritic spines and facilitates synaptogenesis in forebrain neurons.

    PubMed

    Speranza, Luisa; Labus, Josephine; Volpicelli, Floriana; Guseva, Daria; Lacivita, Enza; Leopoldo, Marcello; Bellenchi, Gian Carlo; di Porzio, Umberto; Bijata, Monika; Perrone-Capano, Carla; Ponimaskin, Evgeni

    2017-01-25

    Precise control of dendritic spine density and synapse formation is critical for normal and pathological brain functions. Therefore, signaling pathways influencing dendrite outgrowth and remodeling remain a subject of extensive investigations. Here we report that prolonged activation of the serotonin 5-HT7 receptor (5-HT7R) with selective agonist LP-211 promotes formation of dendritic spines and facilitates synaptogenesis in postnatal cortical and striatal neurons. Critical role of 5-HT7R in neuronal morphogenesis was confirmed by analysis of neurons isolated from 5-HT7R-deficient mice and by pharmacological inactivation of the receptor. Acute activation of 5-HT7R results in pronounced neurite elongation in postnatal striatal and cortical neurons, thus extending previous data on the morphogenic role of 5-HT7R in embryonic and hippocampal neurons. We also observed decreased number of spines in neurons with either genetically (i.e. 5-HT7R-KO) or pharmacologically (i.e. antagonist treatment) blocked 5-HT7R, suggesting that constitutive 5-HT7R activity is critically involved in the spinogenesis. Moreover, cyclin-dependent kinase 5 (Cdk5) and small GTPase Cdc42 were identified as important downstream effectors mediating morphogenic effects of 5-HT7R in neurons. Altogether, our data suggest that the 5-HT7R-mediated structural reorganization during the postnatal development might have a crucial role for the development and plasticity of forebrain areas such as cortex and striatum, and thereby can be implicated in regulation of the higher cognitive functions. This article is protected by copyright. All rights reserved.

  7. Targeting the Serotonin 5-HT7 Receptor in the Search for Treatments for CNS Disorders: Rationale and Progress to Date.

    PubMed

    Nikiforuk, Agnieszka

    2015-04-01

    The 5-HT7 (5-hydroxytryptamine 7, serotonin 7) receptor is one of the most recently identified members of the serotonin receptor family. Pharmacological tools, including selective antagonists and, more recently, agonists, along with 5-HT7 receptor (5-HT7R) knock-out mice have revealed the involvement of this receptor in central nervous system processes. Its well-established role in controlling body temperature and regulating sleep and circadian rhythms has implicated this receptor in mood disorders. Thus, the 5-HT7R has gained much attention as a possible target for the treatment of depression. Although preclinical data support the antidepressant-like actions of 5-HT7R antagonists, their clinical efficacy has not been yet established. Other evidence has implicated the 5-HT7R in learning and memory. Preclinical findings suggest that blockade of this receptor may be beneficial against schizophrenia-like cognitive deficits. Other possible indications include nociception, epilepsy, migraine, autism spectrum disorders, and Rett Syndrome. However, the question is whether the beneficial effects may be achieved by activation or blockade of 5-HT7Rs. Hence, this review briefly summarises the recent findings on the role of 5-HT7Rs and their ligands in CNS disorders.

  8. [Discussion on disease spectrum treated with acupuncture at shenmen (HT 7) and its compatibility based on bibliometrics].

    PubMed

    Feng, Shu-Wei; Zeng, Fang; Ren, Yu-Lan; Liang, Fan-Rong

    2014-06-01

    The modern literatures on the diseases treated with acupuncture at Shenmen (HT 7) were collected. Using literature statistical analysis in bibliometrics, the common compatibility of Shenmen (HT 7) and the disease spectrum were analyzed so as to provide the references of the diseases that can be treated with acupuncture at Shenmen (HT 7). It was found that 39 kinds of diseases and symptoms, mainly nerve system disedses, could be treated with acupuncture at Shenmen (HT 7), including insomnia, depression, anxiety and dementia. Shenmen (HT 7) was seldom used alone. Instead, it was commonly used along with Baihui (GV 20), Sanyinjiao (SP 6), Neiguan (PC 6), Sishencong (EX-HN 1) and Taicong (LR 3).

  9. The atypical antipsychotics clozapine and olanzapine promote down-regulation and display functional selectivity at human 5-HT7 receptors

    PubMed Central

    Andressen, K W; Manfra, O; Brevik, C H; Ulsund, A H; Vanhoenacker, P; Levy, F O; Krobert, K A

    2015-01-01

    Background and Purpose Classically, ligands of GPCRs have been classified primarily upon their affinity and efficacy to activate a signal transduction pathway. Recent reports indicate that the efficacy of a particular ligand can vary depending on the receptor-mediated response measured (e.g. activating G proteins, other downstream responses, internalization). Previously, we reported that inverse agonists induce both homo- and heterologous desensitization, similar to agonist stimulation, at the Gs-coupled 5-HT7 receptor. The primary objective of this study was to determine whether different inverse agonists at the 5-HT7 receptor also induce internalization and/or degradation of 5-HT7 receptors. Experimental Approach HEK293 cells expressing 5-HT7(a, b or d) receptors were pre-incubated with 5-HT, clozapine, olanzapine, mesulergine or SB269970 and their effects upon receptor density, AC activity, internalization, recruitment of β-arrestins and lysosomal trafficking were measured. Key Results The agonist 5-HT and three out of four inverse agonists tested increased internalization independently of β-arrestin recruitment. Among these, only the atypical antipsychotics clozapine and olanzapine promoted lysosomal sorting and reduced 5-HT7 receptor density (∼60% reduction within 24 h). Inhibition of lysosomal degradation with chloroquine blocked the clozapine- and olanzapine-induced down-regulation of 5-HT7 receptors. Incubation with SB269970 decreased both 5-HT7(b) constitutive internalization and receptor density but increased 5-HT7(d) receptor density, indicating differential ligand regulation among the 5-HT7 splice variants. Conclusions and Implications Taken together, we found that various ligands differentially activate regulatory processes governing receptor internalization and degradation in addition to signal transduction. Thus, these data extend our understanding of functional selectivity at the 5-HT7 receptor. PMID:25884989

  10. 5-HT7 receptors and tryptophan hydroxylase in lymphocytes of rats: mitogen activation, physical restraint or treatment with reserpine.

    PubMed

    Urbina, Mary; Arroyo, Rubén; Lima, Lucimey

    2014-01-01

    Serotonin (5-HT)7 receptors in lymphocytes play a relevant role as modulators of T cell functions and might be modified by stress protocols. The aims of this work were to evaluate: (i) the presence of 5-HT7 receptors in specific lymphocyte populations, (ii) the probable modifications of them by inflammatory stress with mitogen and (iii) the effects of physical and pharmacological stress. Blood lymphocytes were isolated by density gradients and differential adhesion to plastic. Concanavalin A (Con A) was systemically administered (500 μg/kg) or added to lymphocyte cultures (2.5 μg/ml, final volume 200 μl). Physical restraint was performed in Plexiglass boxes for 5 h per day for 5 days. Reserpine administration was 2.5 mg/kg for 3 days. Immunocytochemical labeling of CD4+, CD8+ and 5-HT7 receptors, and also tryptophan hydroxylase cells was performed. mRNA of 5-HT7 receptors was evaluated by RT-PCR. Controls were included for each protocol. Con A treatment or culture exposure increased the number of lymphocytes expressing 5-HT7 receptors or tryptophan hydroxylase, as compared to absence of the mitogen. Receptors were present in 12-16% of total rat lymphocytes, in ∼10% of CD4+ and in ∼5% of CD8+ cells from control rats. CD4+ decreased, and CD8+ and 5-HT7 cells increased after physical restraint. Reserpine treatment elevated CD8+ and 5-HT7 cells. Con A and physical restraint, but not reserpine treatment, significantly augmented 5-HT7 receptor mRNA in lymphocytes. Rat lymphocytes, expressing tryptophan hydroxylase, could synthesize 5-HT, functioning as a direct autocrine modulator. The modifications of CD4+, CD8+ and 5-HT7 receptors in lymphocytes by three stress protocols could have an impact on immune responses. In addition, the differential distribution of 5-HT7 receptors indicates potential specific physiopathological roles. © 2014 S. Karger AG, Basel.

  11. Serotonin 5-HT7 receptor is critically involved in acute and chronic inflammation of the gastrointestinal tract.

    PubMed

    Guseva, Daria; Holst, Katrin; Kaune, Beate; Meier, Martin; Keubler, Lydia; Glage, Silke; Buettner, Manuela; Bleich, André; Pabst, Oliver; Bachmann, Oliver; Ponimaskin, Evgeni G

    2014-09-01

    Intestinal inflammation is often associated with an increased level of serotonin (5-HT), an important gastrointestinal signaling molecule involved in gut homeostasis through stimulation of specific receptors. In this study, we investigated the role of 5-HT7 receptor (5-HT7R) in the induction and development of intestinal inflammation using a mouse model of acute and chronic colitis and human patients with Crohn's disease (CD). Acute colitis was induced through administration of dextran sodium sulfate to wild-type, 5-HT7R-deficient mice and hematopoietic bone marrow chimera. Chronic colitis was induced in interleukin 10-deficient mice. The role of 5-HT7R in gut inflammation was assessed using agonist/antagonist treatment. We investigated expression and distribution of 5-HT7R, extent of gut inflammation with magnetic resonance imaging and histological analysis, survival rate, and disease activity index. Finally, biopsies from the large intestine of patients with CD were analyzed. Under basal conditions, 5-HT7R is expressed both in enteric neurons and CD11c cells of the large intestine. Expression of 5-HT7R significantly increased after induction of colitis in mice and in inflamed intestinal regions of patients with CD in CD11c/CD86 double-positive cells. Pharmacological blockade or genetic ablation of 5-HT7R resulted in increased severity of both acute and chronic dextran sodium sulfate-induced colitis, whereas receptor stimulation showed an anti-inflammatory effect. Analysis of bone marrow chimera indicated importance of 5-HT7R expressed by hematopoietic cells in intestinal inflammation. The 5-HT7R expressed on CD11c/CD86-positive myeloid cells modulates the severity of intestinal inflammation in an acute and chronic colitis and thus represents a potential therapeutic target for the treatment of inflammatory disorders such as CD.

  12. Novel highly potent serotonin 5-HT7 receptor ligands: structural modifications to improve pharmacokinetic properties.

    PubMed

    Lacivita, Enza; Di Pilato, Pantaleo; Stama, Madia Letizia; Colabufo, Nicola Antonio; Berardi, Francesco; Perrone, Roberto; De Filippis, Bianca; Laviola, Giovanni; Adriani, Walter; Niso, Mauro; Leopoldo, Marcello

    2013-11-15

    Here we report the synthesis, pharmacological and pharmacokinetic evaluation of a pilot set of compounds structurally related to the potent and selective 5-HT7 ligand LP-211. Among the studied compounds, N-pyridin-3-ylmethyl-3-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]ethoxy]propanamide (4b) showed high affinity for 5-HT7 receptors (K(i)=23.8 nM), selectivity over 5-HT1A receptors (>50-fold), in vitro metabolic stability (82%) and weak interaction with P-glycoprotein (BA/AB=3.3). Compound 4b was injected ip in mice to preliminarily evaluate its distribution between blood and brain.

  13. Design of novel quinazolinone derivatives as inhibitors for 5HT7 receptor.

    PubMed

    Chitta, Aparna; Jatavath, Mohan Babu; Fatima, Sabiha; Manga, Vijjulatha

    2012-02-01

    To study the pharmacophore properties of quinazolinone derivatives as 5HT(7) inhibitors, 3D QSAR methodologies, namely Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) were applied, partial least square (PLS) analysis was performed and QSAR models were generated. The derived model showed good statistical reliability in terms of predicting the 5HT(7) inhibitory activity of the quinazolione derivative, based on molecular property fields like steric, electrostatic, hydrophobic, hydrogen bond donor and hydrogen bond acceptor fields. This is evident from statistical parameters like q(2) (cross validated correlation coefficient) of 0.642, 0.602 and r(2) (conventional correlation coefficient) of 0.937, 0.908 for CoMFA and CoMSIA respectively. The predictive ability of the models to determine 5HT(7) antagonistic activity is validated using a test set of 26 molecules that were not included in the training set and the predictive r(2) obtained for the test set was 0.512 & 0.541. Further, the results of the derived model are illustrated by means of contour maps, which give an insight into the interaction of the drug with the receptor. The molecular fields so obtained served as the basis for the design of twenty new ligands. In addition, ADME (Adsorption, Distribution, Metabolism and Elimination) have been calculated in order to predict the relevant pharmaceutical properties, and the results are in conformity with required drug like properties.

  14. High-affinity interactions of ligands at recombinant Guinea pig 5HT7 receptors

    NASA Astrophysics Data System (ADS)

    Wilcox, R. E.; Ragan, J. E.; Pearlman, R. S.; Brusniak, M. Y.-. K.; Eglen, R. M.; Bonhaus, D. W.; Tenner, T. E., Jr.; Miller, J. D.

    2001-10-01

    The serotonin 5HT7 receptor has been implicated in numerous physiological and pathological processes from circadian rhythms [1] to depression and schizophrenia. Clonal cell lines heterologously expressing recombinant receptors offer good models for understanding drug-receptor interactions and development of quantitative structure-activity relationships (QSAR). Comparative Molecular Field Analysis (CoMFA) is an important modern QSAR procedure that relates the steric and electrostatic fields of a set of aligned compounds to affinity. Here, we utilized CoMFA to predict affinity for a number of high-affinity ligands at the recombinant guinea pig 5HT7 receptor. Using R-lisuride as the template, a final CoMFA model was derived using procedures similar to those of our recent papers [2, 3, 4] The final cross-validated model accounted for >85% of the variance in the compound affinity data, while the final non-cross validated model accounted for >99% of the variance. Model evaluation was done using cross-validation methods with groups of 5 ligands. Twenty cross-validation runs yielded an average predictive r2(q2) of 0.779 ± 0.015 (range: 0.669-0.867). Furthermore, 3D-chemical database search queries derived from the model yielded hit lists of promising agents with high structural similarity to the template. Together, these results suggest a possible basis for high-affinity drug action at 5HT7 receptors.

  15. Interplay between serotonin 5-HT1A and 5-HT7 receptors in depressive disorders.

    PubMed

    Naumenko, Vladimir S; Popova, Nina K; Lacivita, Enza; Leopoldo, Marcello; Ponimaskin, Evgeni G

    2014-07-01

    Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter regulating a wide range of physiological and pathological functions via activation of heterogeneously expressed 5-HT receptors. Besides the important role of 5-HT receptors in the pathogenesis of depressive disorders and in their clinical medications, underlying mechanisms are far from being completely understood. This review focuses on possible cross talk between two serotonin receptors, 5-HT1A and the 5-HT7 . Although these receptors are highly co-expressed in brain regions implicated in depression, and most agonists developed for the 5-HT1A or 5-HT7 receptors have cross-reactivity, their functional interaction has not been yet established. It has been recently shown that 5-HT1A and 5-HT7 receptors form homo- and heterodimers both in vitro and in vivo. From the functional point of view, heterodimerization has been shown to play an important role in regulation of receptor-mediated signaling and internalization, suggesting the implication of heterodimerization in the development and maintenance of depression. Interaction between these receptors is also of clinical interest, because both receptors represent an important pharmacological target for the treatment of depression and anxiety.

  16. 5-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin.

    PubMed

    Kusek, Magdalena; Sowa, Joanna; Kamińska, Katarzyna; Gołembiowska, Krystyna; Tokarski, Krzysztof; Hess, Grzegorz

    2015-01-01

    The 5-HT7 receptor is one of the several serotonin (5-HT) receptor subtypes that are expressed in the dorsal raphe nucleus (DRN). Some earlier findings suggested that 5-HT7 receptors in the DRN were localized on GABAergic interneurons modulating the activity of 5-HT projection neurons. The aim of the present study was to find out how the 5-HT7 receptor modulates the GABAergic synaptic input to putative 5-HT DRN neurons, and whether blockade of the 5-HT7 receptor would affect the release of 5-HT in the target structure. Male Wistar rats with microdialysis probes implanted in the prefrontal cortex (PFC) received injections of the 5-HT7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB 269970), which induced an increase in the levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the PFC. In another set of experiments whole-cell recordings from presumed projection neurons were carried out using DRN slices. SB 269970 application resulted in depolarization and in an increase in the firing frequency of the cells. In order to activate 5-HT7 receptors, 5-carboxamidotryptamine (5-CT) was applied in the presence of N-[2-[4-(2-methoxyphenyl)-1piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635). Hyperpolarization of cells and a decrease in the firing frequency were observed after activation of the 5-HT7 receptor. Blockade of 5-HT7 receptors caused a decrease in the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), while its activation induced an increase. The mechanism of these effects appears to involve tonically-active 5-HT7 receptors modulating firing and/or GABA release from inhibitory interneurons which regulate the activity of DRN serotonergic projection neurons.

  17. Evaluation of 5-HT7 receptor expression in the placentae of normal and pre-eclamptic women.

    PubMed

    Irge, Emine; Halici, Zekai; Yilmaz, Mehmet; Cadirci, Elif; Karakus, Emre

    2016-01-01

    In this study, by examining 5-HT7 receptor expression in placentae from pre-eclamptic and normal pregnancies, we aimed to discover a new step of pathophysiological cascade for preeclampsia. Patients whose blood pressure over the 140/90 mmHg were included when study after 20 weeks of gestation. 5-HT7 receptor expression was investigated on the placentae obtained after birth by real time PCR (RT-PCR) analysis. Pre-natal-post-natal, systolic-diastolic blood pressure values, proteinuria and renal function indicators as BUN and creatinine levels of pre-eclamptic pregnant women were higher than the healthy group. Similarly, 5-HT7 receptor expression determined in healthy placentae increased 8-fold in pre-eclamptic women. This study, for the first time we showed 5-HT7 receptor expression in normal placenta and increased expression in pre-eclamptic placenta.

  18. The 5-HT7 receptor as a potential target for treating drug and alcohol abuse

    PubMed Central

    Hauser, Sheketha R.; Hedlund, Peter B.; Roberts, Amanda J.; Sari, Youssef; Bell, Richard L.; Engleman, Eric A.

    2015-01-01

    Alcohol and drug abuse take a large toll on society and affected individuals. However, very few effective treatments are currently available to treat alcohol and drug addiction. Basic and clinical research has begun to provide some insights into the underlying neurobiological systems involved in the addiction process. Several neurotransmitter pathways have been implicated and distinct reward neurocircuitry have been proposed—including the mesocorticolimbic dopamine (MCL-DA) system and the extended amygdala. The serotonin (5-HT) neurotransmitter system is of particular interest and multiple 5-HT receptors are thought to play significant roles in alcohol and drug self-administration and the development of drug dependence. Among the 5-HT receptors, the 5-HT7 receptor is currently undergoing characterization as a potential target for the treatment of several psychiatric disorders. Although this receptor has received only limited research regarding addictive behaviors, aspects of its neuroanatomical, biochemical, physiological, pharmacological, and behavioral profiles suggest that it could play a key role in the addiction process. For instance, genomic studies in humans have suggested a link between variants in the gene encoding the 5-HT7 receptor and alcoholism. Recent behavioral testing using high-affinity antagonists in mice and preliminary tests with alcohol-preferring rats suggest that this receptor could mediate alcohol consumption and/or reinforcement and play a role in seeking/craving behavior. Interest in the development of new and more selective pharmacological agents for this receptor will aid in examining the 5-HT7 receptor as a novel target for treating addiction. PMID:25628528

  19. The 5-HT7 receptor as a potential target for treating drug and alcohol abuse.

    PubMed

    Hauser, Sheketha R; Hedlund, Peter B; Roberts, Amanda J; Sari, Youssef; Bell, Richard L; Engleman, Eric A

    2014-01-01

    Alcohol and drug abuse take a large toll on society and affected individuals. However, very few effective treatments are currently available to treat alcohol and drug addiction. Basic and clinical research has begun to provide some insights into the underlying neurobiological systems involved in the addiction process. Several neurotransmitter pathways have been implicated and distinct reward neurocircuitry have been proposed-including the mesocorticolimbic dopamine (MCL-DA) system and the extended amygdala. The serotonin (5-HT) neurotransmitter system is of particular interest and multiple 5-HT receptors are thought to play significant roles in alcohol and drug self-administration and the development of drug dependence. Among the 5-HT receptors, the 5-HT7 receptor is currently undergoing characterization as a potential target for the treatment of several psychiatric disorders. Although this receptor has received only limited research regarding addictive behaviors, aspects of its neuroanatomical, biochemical, physiological, pharmacological, and behavioral profiles suggest that it could play a key role in the addiction process. For instance, genomic studies in humans have suggested a link between variants in the gene encoding the 5-HT7 receptor and alcoholism. Recent behavioral testing using high-affinity antagonists in mice and preliminary tests with alcohol-preferring rats suggest that this receptor could mediate alcohol consumption and/or reinforcement and play a role in seeking/craving behavior. Interest in the development of new and more selective pharmacological agents for this receptor will aid in examining the 5-HT7 receptor as a novel target for treating addiction.

  20. S100B interacts with the serotonin 5-HT7 receptor to regulate a depressive-like behavior.

    PubMed

    Stroth, Nikolas; Svenningsson, Per

    2015-12-01

    The serotonin 5-HT7 receptor (5-HT7) is an emerging target for psychiatric pharmacotherapy. Recent observations in rodent models and humans suggest that its blockade mediates antidepressant efficacy. In the present study, we identify the Ca(2+)-binding protein S100B as an interacting partner of 5-HT7 and show that S100B negatively regulates inducible cyclic AMP (cAMP) accumulation in transfected HeLa cells and mouse cortical astrocytes. Overexpression of S100B causes brain region-specific dysregulation of the cAMP pathway in vivo, such that concentrations of cAMP in the frontal cortex are higher in S100B transgenic female mice compared to wild-types. Finally, S100B transgenic female mice show depressive-like behavior in the forced swim test (FST) and pharmacological blockade of 5-HT7 with SB269970 normalizes FST behavior. Taken together, our results show that S100B affects behavioral despair in female mice through functional interaction with the 5-HT7 receptor. Furthermore, we identify S100B as a cAMP-regulatory protein in cultured astrocytes and the murine frontal cortex. Future experiments will clarify whether there is a direct link between the 5-HT7-associated and cAMP-regulatory actions of S100B.

  1. Novel insights into the potential involvement of 5-HT7 receptors in endocrine dysregulation in stress-related disorders.

    PubMed

    Terrón, José A

    2014-01-01

    A hyperactive hypothalamic-pituitary-adrenal (HPA) axis is a common feature of stress-related disorders, and the brain serotonin (5-HT) system plays a major role in HPA axis modulation. Glucocorticoids and stress profoundly affect the 5-HT system so it is possible that alterations of endocrine 5-HT mechanisms may underlie HPA axis overdrive in stress-related diseases. Available evidence suggests a role of 5-HT1A, 5-HT2A/2C and 5-HT7 receptors in HPA system activation, and pharmacological blockade of 5-HT7 receptors produces a fast-acting antidepressant-like action and shortens the onset of antidepressant-like effects of various classes of antidepressants. The mechanisms involved in this effect have not been elucidated, but recent findings suggest a role of 5-HT7 receptors in the development of HPA axis overdrive as a result of chronic stress. Remarkably, clinical findings have shown an association between corticosteroid-producing adenomas and expression of ectopic 5-HT7 receptors in corticosteroid-producing adrenocortical cells. These observations might therefore reveal an endocrine mechanism for the antidepressant-like action of 5-HT7 receptor blockers, possibly through normalization of HPA axis function. If such a preliminary hypothesis is confirmed, the potential therapeutic usefulness of 5-HT7 receptor antagonists could extend beyond depression to include other diseases, the pathophysiology of which has been associated with chronic stress and HPA axis dysregulation.

  2. Activation of 5-HT7 receptor stimulates neurite elongation through mTOR, Cdc42 and actin filaments dynamics.

    PubMed

    Speranza, Luisa; Giuliano, Teresa; Volpicelli, Floriana; De Stefano, M Egle; Lombardi, Loredana; Chambery, Angela; Lacivita, Enza; Leopoldo, Marcello; Bellenchi, Gian C; di Porzio, Umberto; Crispino, Marianna; Perrone-Capano, Carla

    2015-01-01

    Recent studies have indicated that the serotonin receptor subtype 7 (5-HT7R) plays a crucial role in shaping neuronal morphology during embryonic and early postnatal life. Here we show that pharmacological stimulation of 5-HT7R using a highly selective agonist, LP-211, enhances neurite outgrowth in neuronal primary cultures from the cortex, hippocampus and striatal complex of embryonic mouse brain, through multiple signal transduction pathways. All these signaling systems, involving mTOR, the Rho GTPase Cdc42, Cdk5, and ERK, are known to converge on the reorganization of cytoskeletal proteins that subserve neurite outgrowth. Indeed, our data indicate that neurite elongation stimulated by 5-HT7R is modulated by drugs affecting actin polymerization. In addition, we show, by 2D Western blot analyses, that treatment of neuronal cultures with LP-211 alters the expression profile of cofilin, an actin binding protein involved in microfilaments dynamics. Furthermore, by using microfluidic chambers that physically separate axons from the soma and dendrites, we demonstrate that agonist-dependent activation of 5-HT7R stimulates axonal elongation. Our results identify for the first time several signal transduction pathways, activated by stimulation of 5-HT7R, that converge to promote cytoskeleton reorganization and consequent modulation of axonal elongation. Therefore, the activation of 5-HT7R might represent one of the key elements regulating CNS connectivity and plasticity during development.

  3. Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats.

    PubMed

    Cadirci, Elif; Halici, Zekai; Bayir, Yasin; Albayrak, Abdulmecit; Karakus, Emre; Polat, Beyzagul; Unal, Deniz; Atamanalp, Sabri S; Aksak, Selina; Gundogdu, Cemal

    2013-10-01

    Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality.

  4. [Role of brain 5-HT7 receptors as a functional molecule involved in the development of stress adaptation].

    PubMed

    Tsuji, Minoru; Takeuchi, Tomoko; Miyagawa, Kazuya; Takeda, Hiroshi

    2012-08-01

    A growing body of evidence suggests that the brain serotonin (5-HT) nervous system is an important component related to the etiology as well as the treatment of stress-related psychiatric disorders. Molecular cloning studies have revealed the existence of 14 different genes, each encoding a distinct 5-HT receptor subtype. The 5-HT7 receptor is the most recently identified member of the 5-HT receptor subtypes, and the physiological role of this receptor is still unknown. Recently, either selective agonists or antagonists for 5-HT7 receptors, as well as 5-HT7 receptor knockout mice, have been developed, and these have recently been used as the experimental tools for determining the actual function of 5-HT7 receptors. The first half of the present article introduces the reports that have examined the role of the 5-HT7 receptor on emotional regulation. On the other hand, it has been indicated that the ability to adapt to stress is an important defensive function of a living body, and impairment of this ability may contribute to some stress-related disorders. Thus, the examination of brain mechanisms involved in stress adaptation could help to pave the way for new therapeutic strategies for stress-related psychiatric disorders. The second half of the present article introduces our recent studies focusing on the relationship between brain 5-HT7 receptors and the mechanisms of stress adaptation.

  5. Antihyperalgesic effect of 5-HT7 receptor activation on the midbrain periaqueductal gray in a rat model of neuropathic pain.

    PubMed

    Li, Shu-Fa; Zhang, Yuan-Yuan; Li, You-Yan; Wen, Song; Xiao, Zhi

    2014-12-01

    The 5-HT7 receptor is the most recently discovered receptor for 5-hydroxytryptamine (5-HT), and only little is known about the analgesic potential of this receptor. Adenosine triphosphate (ATP) modulates pain transmission by activating P2X/P2Y receptors, in which the P2X3 subtype is an important target for this effect. This study examined the antihyperalgesic effect of the 5-HT7 receptors in the ventrolateral midbrain periaqueductal gray (vlPAG), a crucial site for endogenous pain inhibition. This study also explored the importance of the interactions between the 5-HT7 and P2X3 receptors in this effect. To address this issue, neuropathic pain was induced through chronic constriction injury (CCI) of the sciatic nerve in Sprague-Dawley (SD) rats. The expression level and distribution of the 5-HT7 receptor were evaluated through Western blot and immunohistochemistry. The mechanical withdrawal threshold (MWT) was measured by using an electronic pressure meter test. Different doses (3, 6, and 12μmol) of AS-19, a selective agonist of the 5-HT7 receptor, were administered in the vlPAG of CCI rats. The effects of pretreatment with the selective 5-HT7 receptor antagonist SB-269970 or the selective P2X3 receptor antagonist A-317491 on the analgesic effect of AS-19 were observed. Results showed that CCI decreased the MWT values of the rats. The injury also increased the protein level of the 5-HT7 receptor in the vlPAG of neuropathic pain rats. AS-19 microinjection significantly elevated the MWT values in a dose-dependent manner, but SB-269970 pretreatment attenuated the antihyperalgesic effect of AS-19. Furthermore, the antihyperalgesic effect of the 5-HT7 receptor was partially but significantly blocked by A-317491 pretreatment. These data indicate that the 5-HT7 receptor in the vlPAG exerts an antihyperalgesic effect on rats with neuropathic pain. The 5-HT7 and P2X3 receptors interact in the vlPAG and exhibit an analgesic action through the enhanced function of the

  6. Deqi Induction by HT7 Acupuncture Alters Theta and Alpha Band Coherence in Human Healthy Subjects.

    PubMed

    Lee, Go-Eun; Yun, Jong-Min; Yang, Seung-Bum; Kang, Yeonseok; Kang, Hyung-Won; Choi, Kwang-Ho; Kim, Junbeom; Kwon, O Sang; Park, Ji-Eun; Kim, Jae-Hyo

    2017-01-01

    The aim of this preliminary study is to investigate the changes in phase synchronization in the theta and alpha bands before and during the performance of classical acupuncture on the Sinmun (HT7). The electroencephalogram (EEG) signals from nine healthy young subjects were recorded before and during acupuncture in the "closed-eye" state. The EEG signals were acquired from 19 surface scalp electrodes (FP1, FP2, F7, F3, Fz F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, and O2). Needles were inserted into the HT7 bilaterally and were then manipulated to induce deqi and retained for 15 minutes. Phase synchronization was measured by phase coherence. In the theta band, coherence significantly increased between the temporal (T5, T6) and occipital areas (O1, O2) during the acupuncture stimulation. In the alpha band, coherence significantly increased between the left temporal area (T5) and other areas (frontal, parietal, and occipital). Phase coherence in the theta and alpha bands tended to increase during the retention of the acupuncture needles after deqi. Therefore, it can be concluded that acupuncture stimulation with deqi is clinically effective via the central nervous system (CNS).

  7. Deqi Induction by HT7 Acupuncture Alters Theta and Alpha Band Coherence in Human Healthy Subjects

    PubMed Central

    Choi, Kwang-Ho

    2017-01-01

    The aim of this preliminary study is to investigate the changes in phase synchronization in the theta and alpha bands before and during the performance of classical acupuncture on the Sinmun (HT7). The electroencephalogram (EEG) signals from nine healthy young subjects were recorded before and during acupuncture in the “closed-eye” state. The EEG signals were acquired from 19 surface scalp electrodes (FP1, FP2, F7, F3, Fz F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, and O2). Needles were inserted into the HT7 bilaterally and were then manipulated to induce deqi and retained for 15 minutes. Phase synchronization was measured by phase coherence. In the theta band, coherence significantly increased between the temporal (T5, T6) and occipital areas (O1, O2) during the acupuncture stimulation. In the alpha band, coherence significantly increased between the left temporal area (T5) and other areas (frontal, parietal, and occipital). Phase coherence in the theta and alpha bands tended to increase during the retention of the acupuncture needles after deqi. Therefore, it can be concluded that acupuncture stimulation with deqi is clinically effective via the central nervous system (CNS). PMID:28484506

  8. Characterization of putative 5-HT7 receptors mediating tachycardia in the cat

    PubMed Central

    Villalón, Carlos M; Heiligers, Jan P C; Centurión, David; De Vries, Peter; Saxena, Pramod R

    1997-01-01

    , sumatriptan (30, 100 and 300 μg kg−1) and indorenate (300 and 1000 μg kg−1) or the 5-HT4 receptor (partial) agonist cisapride (300 and 1000 μg kg−1) were devoid of effects on feline heart rate per se and failed to modify significantly 5-HT-induced tachycardic responses. Based upon the above rank order of agonist potency, the failure of sumatriptan, indorenate or cisapride to produce cardioacceleration and the blockade by a series of drugs showing high affinity for the cloned 5-ht7 receptor, the present results indicate that the 5-HT receptor mediating tachycardia in the cat is operationally similar to other putative 5-HT7 receptors mediating vascular and non-vascular responses (e.g. relaxation of the rabbit femoral vein, canine external carotid and coronary arteries, rat systemic vasculature and guinea-pig ileum). Since these responses represent functional correlates of the 5-ht7 gene product, the 5-HT7 receptor appellation is reinforced. Therefore, the present experimental model, which is not complicated by the presence of other 5-HT receptors, can be utilized to characterize and develop new drugs with potential agonist and antagonist properties at functional 5-HT7 receptors. PMID:9249256

  9. The critical role of spinal 5-HT7 receptors in opioid and non-opioid type stress-induced analgesia.

    PubMed

    Yesilyurt, Ozgur; Seyrek, Melik; Tasdemir, Serdar; Kahraman, Serdar; Deveci, Mehmet Salih; Karakus, Emre; Halici, Zekai; Dogrul, Ahmet

    2015-09-05

    The opioid and non-opioid types of stress-induced analgesia have been well defined. One of the non-opioid type involve the endocannabinoid system. We previously reported that the spinal serotonin 7 receptor (5-HT7) blockers inhibit both morphine and cannabinoid-induced analgesia, thus we hypothesized that descending serotonergic pathways-spinal 5-HT7 receptor loop might contribute to stress-induced analgesia. Stress-induced analgesia was induced with warm (32°C) or cold (20°C) water swim stress in male Balb-C mice. The effects of intrathecal injection of a selective 5-HT7 receptor antagonist, SB 269970, of the denervation of serotonergic neurons by intrathecal administration of 5,7-dihydroxytryptamine (5,7-DHT) and of lesions of the dorsolateral funiculus on opioid and non-opioid type stress-induced analgesia were evaluated with the tail-flick and hot plate tests. The expression of 5-HT7 receptors mRNA in the dorsal lumbar region of spinal cord were analyzed by RT-PCR following spinal serotonin depletion or dorsolateral funiculus lesion. The effects of the selective 5-HT7 receptor agonists LP 44 and AS 19 were tested on nociception. Intrathecal SB 269970 blocked both opioid and non-opioid type stress-induced analgesia. Dorsolateral funiculus lesion or denervation of the spinal serotonergic neurons resulted in a marked decrease in 5-HT7 receptor expression in the dorsal lumbar spinal cord, accompanied by inhibition of opioid and non-opioid type stress-induced analgesia. However, the systemic or intrathecal LP 44 and AS 19 alone did not produce analgesia in unstressed mice. These results indicate that descending serotonergic pathways and the spinal 5-HT7 receptor loop play a crucial role in mediating both opioid and non-opioid type stress-induced analgesia.

  10. Effect of 5-HT(7) antagonist SB-269970 in the modulation of working and reference memory in the rat.

    PubMed

    Gasbarri, Antonella; Cifariello, Agata; Pompili, Assunta; Meneses, Alfredo

    2008-12-16

    It has been established that serotonergic pathways project to cerebral areas involved in learning and memory and that serotonin (5-HT) receptor agonists and antagonists modify these processes. Indeed, most of the 5-HT receptors characterized so far, i.e., 5-HT(1) through 5-HT(7), show a regional distribution in brain areas involved in learning and memory, such as hippocampal formation (HF), amygdala and cortex. Although 5-HT(7) receptor biological functions are still to be clarified, it was recently suggested that it may play a role in the control of learning and memory processes. The aim of our study was to assess the role of 5-HT(7) receptors antagonist SB-269970 on working and reference memory in a radial arm maze task, utilizing a two-phase procedure, comprising an acquisition and test phase, conducted to evaluate working and reference memory, respectively. Our results showed that 5-HT(7) receptors antagonist SB-269970 improved memory, decreasing the number of errors in test phase and, thus, affecting reference memory, while no effects were observed in working memory. These results could be explained taking into consideration the specific localization of 5-HT(7) receptors in the CNS. In fact, high concentrations of 5-HT(7) receptors were found in the HF, which exerts an important role on reference memory, while relatively low concentrations were present in the prefrontal cortex, involved in working memory. Thus, 5-HT(7) receptor blockade had procognitive effect, when the learning task implicated a high degree of difficulty. This conclusion has a major implication in the context that 5-HT receptors play an important role under amnesia states (e.g., Alzheimer's disease) or when the learning is complex.

  11. 5-HT7 Receptors Are Not Involved in Neuropeptide Release in Primary Cultured Rat Trigeminal Ganglion Neurons.

    PubMed

    Wang, Xiaojuan; Hu, Rong; Liang, Jianbo; Li, Ze; Sun, Weiwen; Pan, Xiaoping

    2016-06-01

    Migraine is a common but complex neurological disorder. Its precise mechanisms are not fully understood. Increasing indirect evidence indicates that 5-HT7 receptors may be involved; however, their role remains unknown. Our previous in vivo study showed that selective blockade of 5-HT7 receptors caused decreased serum levels of calcitonin gene-related peptide (CGRP) in the external jugular vein following electrical stimulation of the trigeminal ganglion (TG) in an animal model of migraine. In the present study, we used an in vitro model of cultured TG cells to further investigate whether 5-HT7 receptors are directly responsible for the release of CGRP and substance P from TG neurons. We stimulated rat primary cultured TG neurons with capsaicin or potassium chloride (KCl) to mimic neurogenic inflammation, resulting in release of CGRP and substance P. 5-HT7 receptors were abundantly expressed in TG neurons. Greater than 93 % of 5-HT7 receptor-positive neurons co-expressed CGRP and 56 % co-expressed substance P. Both the capsaicin- and KCl-induced release of CGRP and substance P were unaffected by pretreatment of cultured TG cells with the selective 5-HT7 receptor agonist AS19 and antagonist SB269970. This study demonstrates for the first time that 5-HT7 receptors are abundantly co-expressed with CGRP and substance P in rat primary TG neurons and suggests that they are not responsible for the release of CGRP and substance P from cultured TG neurons evoked by capsaicin or KCl.

  12. Serotonin (5-HT) regulates neurite outgrowth through 5-HT1A and 5-HT7 receptors in cultured hippocampal neurons.

    PubMed

    Rojas, Paulina S; Neira, David; Muñoz, Mauricio; Lavandero, Sergio; Fiedler, Jenny L

    2014-08-01

    Serotonin (5-HT) production and expression of 5-HT receptors (5-HTRs) occur early during prenatal development. Recent evidence suggests that, in addition to its classical role as a neurotransmitter, 5-HT regulates neuronal connectivity during mammalian development by modulating cell migration and neuronal cytoarchitecture. Given the variety of 5-HTRs, researchers have had difficulty clarifying the specific role of each receptor subtype in brain development. Signalling mediated by the G-protein-coupled 5-HT1A R and 5-HT7 R, however, has been associated with neuronal plasticity. Thus, we hypothesized that 5-HT promotes neurite outgrowth through 5-HT1A R and 5-HT7 R. The involvement of 5-HT1A R and 5-HT7 R in the morphology of rat hippocampal neurons was evaluated by treating primary cultures at 2 days in vitro with 5-HT and specific antagonists for 5-HT1A R and 5-HT7 R (WAY-100635 and SB269970, respectively). The stimulation of hippocampal neurons with 100 nM 5-HT for 24 hr produced no effect on either the number or the length of primary neurites. Nonetheless, after 5HT7 R was blocked, the addition of 5-HT increased the number of primary neurites, suggesting that 5HT7 R could inhibit neuritogenesis. In contrast, 5-HT induced secondary neurite outgrowth, an effect inhibited by 1 μM WAY-100635 or SB269970. These results suggest that both serotonergic receptors participate in secondary neurite outgrowth. We conclude that 5-HT1A R and 5-HT7 R regulate neuronal morphology in primary hippocampal cultures by promoting secondary neurite outgrowth.

  13. Serotonin 5-HT7 receptor agents: structure-activity relationships and potential therapeutic applications in central nervous system disorders

    PubMed Central

    Leopoldo, Marcello; Lacivita, Enza; Berardi, Francesco; Perrone, Roberto; Hedlund, Peter B.

    2010-01-01

    Since its discovery in the 1940s in serum, the mammalian intestinal mucosa, and in the central nervous system, serotonin (5-HT) has been shown to be involved in virtually all cognitive and behavioral human functions, and alterations in its neurochemistry have been implicated in the etiology of a plethora of neuropsychiatric disorders. The cloning of 5-HT receptor subtypes has been of importance in enabling them to be classified as specific protein molecules encoded by specific genes. The 5-HT7 receptor is the most recently classified member of the serotonin receptor family. Since its identification, it has been the subject of intense research efforts driven by its presence in functionally relevant regions of the brain. The availability of some selective antagonists and agonists, in combination with genetically modified mice lacking the 5-HT7 receptor, has allowed for a better understanding of the pathophysiological role of this receptor. This paper reviews data on localization and pharmacological properties of the 5-HT7 receptor, and summarizes the results of structure-activity relationship studies aimed at the discovery of selective 5-HT7 receptor ligands. Additionally, an overview of the potential therapeutic applications of 5-HT7 receptor agonists and antagonists in central nervous system disorders is presented. PMID:20923682

  14. An mRNA expression analysis of stimulation and blockade of 5-HT7 receptors during memory consolidation.

    PubMed

    Pérez-García, Georgina; Gonzalez-Espinosa, Claudia; Meneses, Alfredo

    2006-04-25

    Despite the compelling support for 5-hydroxytryptamine (5-HT) receptors participation in learning and memory in mammal species, the molecular basis had been largely absent from any discussion of its mechanistic underpinnings. Here, we report that reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that there was a higher level of expression of the investigated 5-HT receptor mRNAs in autoshaping-trained relative to untrained groups. Actually, pharmacological naïve untrained and autoshaping-trained rats showed significant differences, the latter groups expressing, in decreasing order, 5-HT1A < 5-HT6 < 5-HT4 < or = 5-HT7 receptors mRNA in prefrontal cortex and hippocampus. In order to determine more precisely mRNA expression and memory consolidation, we combined selective 5-HT7 receptors stimulation or blockade in the same animals, and brain areas individually analyzed. 5-HT7 receptors were strongly expressed in all the three brain areas of vehicle-trained rats relative to untrained group. The potential selective 5-HT7 receptor agonist AS 19 enhanced memory consolidation, attenuated mRNA receptors expression, and the facilitatory memory effect was reversed by SB-269970. Finally, pharmacological stimulation of 5-HT7 receptors reversed scopolamine- or dizocilpine-induced amnesia and receptor down-regulation.

  15. Towards metabolically stable 5-HT7 receptor ligands: a study on 1-arylpiperazine derivatives and related isosters.

    PubMed

    Lacivita, Enza; De Giorgio, Paola; Patarnello, Daniela; Niso, Mauro; Colabufo, Nicola A; Berardi, Francesco; Perrone, Roberto; Satala, Grzegorz; Duszynska, Beata; Bojarski, Andrzej J; Leopoldo, Marcello

    2013-10-01

    Serotonin 7 (5-hydroxytryptamine7 or 5-HT7) is the most recently identified serotonin receptor. It is involved in mood disorders and is studied as a target for antidepressants. Here, we report on the structural manipulation of the 5-HT7 receptor ligand 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (1a) aimed at obtaining 5-HT7 receptor ligands endowed with good in vitro metabolic stability. A set of N-[3-methoxyphenyl)ethyl-substituted] 1-arylpiperazine, 4-arylpiperidine and 1-aryl-4-aminopiperidine was synthesized and tested in radioligand binding assays at human cloned 5-HT7 and 5-HT1A receptors. In vitro metabolic stability of the target compounds was assessed after incubation with rat hepatic S9 microsomal fraction. Among the new compounds, 1-(2-biphenyl)-4-[2-(3-methoxyphenyl)ethyl]piperazine (1d) and 4-(2-biphenyl)-1-[2-(3-methoxyphenyl)ethyl]piperidine (2d) showed a good compromise between affinity at 5-HT7 receptor (K i = 7.5 nM and 13 nM, respectively) and in vitro metabolic stability (26 and 65 % recovery of parent compound, respectively) but were poorly selective over 5-HT1A receptor.

  16. Selective agonists for serotonin 7 (5-HT7) receptor and their applications in preclinical models: an overview.

    PubMed

    Di Pilato, Pantaleo; Niso, Mauro; Adriani, Walter; Romano, Emilia; Travaglini, Domenica; Berardi, Francesco; Colabufo, Nicola A; Perrone, Roberto; Laviola, Giovanni; Lacivita, Enza; Leopoldo, Marcello

    2014-01-01

    The serotonin 7 (5-HT7) receptor was the last serotonin receptor subtype to be discovered in 1993. This receptor system has been implicated in several central nervous system (CNS) functions, including circadian rhythm, rapid eye movement sleep, thermoregulation, nociception, memory and neuropsychiatric symptoms and pathologies, such as anxiety, depression and schizophrenia. In 1999, medicinal chemistry efforts led to the identification of SB-269970, which became the gold standard selective 5-HT7 receptor antagonist, and later of various selective agonists such as AS-19, LP-44, LP-12, LP-211 and E-55888. In this review, we summarize the preclinical pharmacological studies performed using these agonists, highlighting their strengths and weaknesses. The data indicate that 5-HT7 receptor agonists can have neuroprotective effects against N-methyl-d-aspartate-induced toxicity, modulate neuronal plasticity in rats, enhance morphine-induced antinociception and alleviate hyperalgesia consecutive to nerve lesion in neuropathic animals.

  17. 5-HT(1A) and 5-HT(7) receptors differently modulate AMPA receptor-mediated hippocampal synaptic transmission.

    PubMed

    Costa, L; Trovato, C; Musumeci, S A; Catania, M V; Ciranna, L

    2012-04-01

    We have studied the effects of 5-HT(1A) and 5-HT(7) serotonin receptor activation in hippocampal CA3-CA1 synaptic transmission using patch clamp on mouse brain slices. Application of either 5-HT or 8-OH DPAT, a mixed 5-HT(1A)/5-HT(7) receptor agonist, inhibited AMPA receptor-mediated excitatory post synaptic currents (EPSCs); this effect was mimicked by the 5-HT(1A) receptor agonist 8-OH PIPAT and blocked by the 5-HT(1A) antagonist NAN-190. 8-OH DPAT increased paired-pulse facilitation and reduced the frequency of mEPSCs, indicating a presynaptic reduction of glutamate release probability. In another group of neurons, 8-OH DPAT enhanced EPSC amplitude but did not alter paired-pulse facilitation, suggesting a postsynaptic action; this effect persisted in the presence of NAN-190 and was blocked by the 5-HT(7) receptor antagonist SB-269970. To confirm that EPSC enhancement was mediated by 5-HT(7) receptors, we used the compound LP-44, which is considered a selective 5-HT(7) agonist. However, LP-44 reduced EPSC amplitude in most cells and instead increased EPSC amplitude in a subset of neurons, similarly to 8-OH DPAT. These effects were respectively antagonized by NAN-190 and by SB-269970, indicating that under our experimental condition LP-44 behaved as a mixed agonist. 8-OH DPAT also modulated the current evoked by exogenously applied AMPA, inducing either a reduction or an increase of amplitude in distinct neurons; these effects were respectively blocked by 5-HT(1A) and 5-HT(7) receptor antagonists, indicating that both receptors exert a postsynaptic action. Our results show that 5-HT(1A) receptors inhibit CA3-CA1 synaptic transmission acting both pre- and postsynaptically, whereas 5-HT(7) receptors enhance CA3-CA1 synaptic transmission acting exclusively at a postsynaptic site. We suggest that a selective pharmacological targeting of either subtype may be envisaged in pathological loss of hippocampal-dependent cognitive functions. In this respect, we underline the

  18. Translation of Novel Serotonin 5-HT7 Agonist Drug Candidates in Rodent Models of Fragile X Syndrome

    DTIC Science & Technology

    2016-09-01

    AWARD NUMBER: W81XWH-15-1-0247 TITLE: Translation of Novel Serotonin 5-HT7 Agonist Drug Candidates in Rodent Models of Fragile X Syndrome...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Translation of Novel Serotonin 5-HT7 Agonist Drug Candidates in Rodent Models of Fragile X Syndrome 5b. GRANT...Requirements……………………………………11 4  INTRODUCTION: The subject of this research is preclinical drug discovery and development for Fragile X syndrome. The

  19. 5-HT1A and 5-HT7 receptor crosstalk in the regulation of emotional memory: implications for effects of selective serotonin reuptake inhibitors.

    PubMed

    Eriksson, Therese M; Holst, Sarah; Stan, Tiberiu L; Hager, Torben; Sjögren, Benita; Ogren, Sven Öve; Svenningsson, Per; Stiedl, Oliver

    2012-11-01

    This study utilized pharmacological manipulations to analyze the role of direct and indirect activation of 5-HT(7) receptors (5-HT(7)Rs) in passive avoidance learning by assessing emotional memory in male C57BL/6J mice. Additionally, 5-HT(7)R binding affinity and 5-HT(7)R-mediated protein phosphorylation of downstream signaling targets were determined. Elevation of 5-HT by the selective serotonin reuptake inhibitor (SSRI) fluoxetine had no effect by itself, but facilitated emotional memory performance when combined with the 5-HT(1A)R antagonist NAD-299. This facilitation was blocked by the selective 5-HT(7)R antagonist SB269970, revealing excitatory effects of the SSRI via 5-HT(7)Rs. The enhanced memory retention by NAD-299 was blocked by SB269970, indicating that reduced activation of 5-HT(1A)Rs results in enhanced 5-HT stimulation of 5-HT(7)Rs. The putative 5-HT(7)R agonists LP-44 when administered systemically and AS19 when administered both systemically and into the dorsal hippocampus failed to facilitate memory. This finding is consistent with the low efficacy of LP-44 and AS19 to stimulate protein phosphorylation of 5-HT(7)R-activated signaling cascades. In contrast, increasing doses of the dual 5-HT(1A)R/5-HT(7)R agonist 8-OH-DPAT impaired memory, while co-administration with NAD-299 facilitated of emotional memory in a dose-dependent manner. This facilitation was blocked by SB269970 indicating 5-HT(7)R activation by 8-OH-DPAT. Dorsohippocampal infusion of 8-OH-DPAT impaired passive avoidance retention through hippocampal 5-HT(1A)R activation, while 5-HT(7)Rs appear to facilitate memory processes in a broader cortico-limbic network and not the hippocampus alone.

  20. Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task.

    PubMed

    Meneses, Alfredo

    2004-12-06

    There is an important debate regarding the functional role of the 5-HT(1A) and 5-HT(7) receptor in memory systems. Hence, the objective of this paper is to investigate the function of serotonin (5-hydroxytryptamine, 5-HT) in memory consolidation, utilising an autoshaping Pavlovian/instrumental learning test. Specific antagonists at 5-HT(1A) (WAY 100635) and 5-HT(7) (SB-269970 or DR 4004) receptors administered i.p. or s.c.) after training, significantly decreased the improvement of performance produced by the 5-HT(1A/7) agonist 8-OH-DPAT to levels lower than controls'. These same antagonists attenuated the decreased level of performance produced by mCPP, although they decrease the performance levels after p-chloroamphetamine (PCA) lesion of the 5-HT system, which has no effect on its own on the conditioned response. Moreover, SB-269970 or DR 4004 reversed amnesia induced by scopolamine and dizocilpine. These data confirm a role for 5-HT(1A) and 5-HT(7) receptors in memory formation and support the hypothesis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals. These findings support a potential role for both 5-HT(1A) and 5-HT(7) receptors in the pathophysiology and/or treatment of schizophrenia, cognitive deficits and the mechanism of action of atypical antipsychotic drugs.

  1. Role of 5-HT7 receptors in the inhibition of the vasodepressor sensory CGRPergic outflow in pithed rats.

    PubMed

    Cuesta, Cristina; García-Pedraza, José Ángel; García, Mónica; Villalón, Carlos M; Morán, Asunción

    2014-10-01

    The role of calcitonin gene-related peptide (CGRP) in the modulation of vascular tone has been widely documented. Indeed, electrical stimulation of the perivascular sensory outflow in pithed rats induces vasodepressor responses by activation of CGRP receptors. This study investigated the role of 5-HT7 receptors in the inhibition of the rat vasodepressor sensory outflow. Male Wistar pithed rats were pretreated with i.v. continuous infusions of hexamethonium and methoxamine, followed by physiological saline or AS-19 (a 5-HT7 receptor agonist). Then, electrical stimulation of the spinal cord resulted in frequency-dependent decreases in DBP. The infusions of AS-19, as compared to those of saline, inhibited the vasodepressor responses induced by electrical stimulation without affecting those to i.v. bolus injections of exogenous α-CGRP. This inhibition by AS-19 was abolished by the antagonists pimozide (5-HT7) or sulfisoxazole (ETA), but not by indomethacin (COX1/2) or losartan (AT1), at doses that did not affect per se the electrically-induced vasodepressor responses. Interestingly, glibenclamide (an ATP-dependent K(+) channel blocker) attenuated these vasodepressor responses. The present results suggest that AS-19-induced inhibition of the rat vasodepressor sensory CGRPergic outflow is mainly mediated by 5-HT7 receptors via endothelin release, with the possible involvement of ATP-dependent K(+) channels.

  2. The effects of combining serotonin reuptake inhibition and 5-HT7 receptor blockade on circadian rhythm regulation in rodents.

    PubMed

    Westrich, Ligia; Sprouse, Jeffrey; Sánchez, Connie

    2013-02-17

    Disruption of circadian rhythms may lead to mood disorders. The present study investigated the potential therapeutic utility of combining a 5-HT7 antagonist with a selective serotonin (5-HT) reuptake inhibitor (SSRI), the standard of care in depression, on circadian rhythm regulation. In tissue explants of the suprachiasmatic nucleus (SCN) from PER2::LUC mice genetically modified to report changes in the expression of a key clock protein, the period length of PER2 bioluminescence was shortened in the presence of AS19, a 5-HT7 partial agonist. This reduction was blocked by SB269970, a selective 5-HT7 antagonist. The SSRI, escitalopram, had no effect alone on period length, but a combination with SB269970, yielded significant increases. Dosed in vivo, escitalopram had little impact on the occurrence of activity onsets in rats given access to running wheels, whether the drug was given acutely or sub-chronically. However, preceding the escitalopram treatment with a single acute dose of SB269970 produced robust phase delays, in keeping with the in vitro explant data. Taken together, these findings suggest that the combination of an SSRI and a 5-HT7 receptor antagonist has a greater impact on circadian rhythms than that observed with either agent alone, and that such a multimodal approach may be of therapeutic value in treating patients with poor clock function.

  3. Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: Involvement of 5-HT7 receptors

    PubMed Central

    García-Iglesias, Brenda B.; Mendoza-Garrido, María E.; Gutiérrez-Ospina, Gabriel; Rangel-Barajas, Claudia; Noyola-Díaz, Martha; Terrón, José A.

    2013-01-01

    Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB-656104 (a 5-HT7 receptor antagonist); 2) 5-HT7 receptor-like immunoreactivity (5-HT7-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal glands (AG); 3) baseline levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA), and 5-HIAA/5-HT ratio in PVN and AG; and 4) 5-HT-like immunoreactivity (5-HT-LI) in AG and tryptophan hydroxylase (TPH) protein in PVN and AG. On day 15, animals were subdivided into Treatment and No treatment groups. Treatment animals received an i.p. injection of vehicle or SB-656104; No Treatment animals received no injection. Sixty min later, Treatment animals were either decapitated with no further stress (0 min) or submitted to acute restraint (10, 30, 60 or 120 min); hormone serum levels were measured. No Treatment animals were employed for the rest of measurements. CRS decreased body weight gain and increased adrenal weight. In CTRL animals, acute restraint increased ACTH and CORT secretion in a time of restraint-dependent manner; both responses were inhibited by SB-656104. Exposure to CRS abolished ACTH but magnified CORT responses to restraint as compared to CTRL conditions; SB-656104 had no effect on ACTH levels but significantly inhibited sensitized CORT responses. In CTRL animals, 5-HT7-LI was detected in magnocellular and parvocellular subdivisions of PVN and sparsely in adrenal cortex. Exposure to CRS decreased 5-HT7-LI and protein in the PVN, but increased 5-HT7-LI in the adrenal cortex and protein in whole AG. Higher 5-HT and 5-HIAA levels were detected in PVN and AG from CRS animals but 5-HIAA/5-HT ratio increased in AG only. Finally, whereas 5-HT-LI was sparsely observed in the adrenal cortex

  4. Spinal 5-HT7 receptors and protein kinase A constrain intermittent hypoxia-induced phrenic long-term facilitation.

    PubMed

    Hoffman, M S; Mitchell, G S

    2013-10-10

    Phrenic long-term facilitation (pLTF) is a form of serotonin-dependent respiratory plasticity induced by acute intermittent hypoxia (AIH). pLTF requires spinal Gq protein-coupled serotonin-2 receptor (5-HT2) activation, new synthesis of brain-derived neurotrophic factor (BDNF) and activation of its high-affinity receptor, TrkB. Intrathecal injections of selective agonists for Gs protein-coupled receptors (adenosine 2A and serotonin-7; 5-HT7) also induce long-lasting phrenic motor facilitation via TrkB "trans-activation." Since serotonin released near phrenic motor neurons may activate multiple serotonin receptor subtypes, we tested the hypothesis that 5-HT7 receptor activation contributes to AIH-induced pLTF. A selective 5-HT7 receptor antagonist (SB-269970, 5mM, 12 μl) was administered intrathecally at C4 to anesthetized, vagotomized and ventilated rats prior to AIH (3, 5-min episodes, 11% O2). Contrary to predictions, pLTF was greater in SB-269970 treated versus control rats (80 ± 11% versus 45 ± 6% 60 min post-AIH; p<0.05). Hypoglossal LTF was unaffected by spinal 5-HT7 receptor inhibition, suggesting that drug effects were localized to the spinal cord. Since 5-HT7 receptors are coupled to protein kinase A (PKA), we tested the hypothesis that PKA inhibits AIH-induced pLTF. Similar to 5-HT7 receptor inhibition, spinal PKA inhibition (KT-5720, 100 μM, 15 μl) enhanced pLTF (99 ± 15% 60 min post-AIH; p<0.05). Conversely, PKA activation (8-br-cAMP, 100 μM, 15 μl) blunted pLTF versus control rats (16 ± 5% versus 45 ± 6% 60 min post-AIH; p<0.05). These findings suggest a novel mechanism whereby spinal Gs protein-coupled 5-HT7 receptors constrain AIH-induced pLTF via PKA activity.

  5. Chronic Sarpogrelate Treatment Reveals 5-HT7 Receptor in the Serotonergic Inhibition of the Rat Vagal Bradycardia.

    PubMed

    García-Pedraza, José Ángel; García, Mónica; Martín, María Luisa; Eleno, Nélida; Morán, Asunción

    2017-01-01

    5-Hydroxytryptamine (5-HT) modulates the cardiac parasympathetic neurotransmission, inhibiting the bradyarrhythmia by 5-HT2 receptor activation. We aimed to determine whether the chronic selective 5-HT2 blockade (sarpogrelate) could modify the serotonergic modulation on vagal cardiac outflow in pithed rat. Bradycardic responses in rats treated with sarpogrelate (30 mg·kg·d; orally) were obtained by electrical stimulation of the vagal fibers (3, 6, and 9 Hz) or intravenous (IV) injections of acetylcholine (1, 5, and 10 μg/kg). 5-HT7 receptor expression was quantified by Western blot in vagus nerve and right atrium. The IV administration of 5-HT (10-200 μg/kg) dose dependently decreased the vagally induced bradycardia, and agonists 5-CT (5-HT1/7), 8-OH-DPAT (5-HT1A), or AS-19 (5-HT7) (50 μg/kg each) mimicked the 5-HT-induced inhibitory effect. Neither agonists CGS-12066B (5-HT1B), L-694,247 (5-HT1D), nor 1-phenylbiguanide (5-HT3) modified the electrically-induced bradycardic responses. Moreover, SB-258719 (5-HT7 antagonist) abolished the 5-HT-, 5-CT-, 8-OH-DPAT-, and AS-19-induced bradycardia inhibition; 5-HT or AS-19 did not modify the bradycardia induced by IV acetylcholine; and 5-HT7 receptor was expressed in both the vagus nerve and the right atrium. Our outcomes suggest that blocking chronically 5-HT2 receptors modifies the serotonergic influence on cardiac vagal neurotransmission exhibiting 5-HT as an exclusively inhibitory agent via prejunctional 5-HT7 receptor.

  6. Selective blockade of 5-HT7 receptors facilitates attentional set-shifting in stressed and control rats.

    PubMed

    Nikiforuk, Agnieszka

    2012-01-01

    Preclinical data demonstrate that the selective blockade of 5-HT7 receptors produces antidepressant-like behavioural effects. Although the involvement of 5-HT7 receptors in cognitive processes has been previously suggested, little is known about their role in the prefrontal cortex (PFC)-dependent processes that may be impaired in stress-related states. According to our previous study, repeated restraint stress induces the long-lasting cognitive impairment in a rat model of PFC-dependent attentional set-shifting task (ASST). Therefore, the first aim of the present experiments was to examine the impact of the selective 5-HT7 receptor antagonist, SB-269970, on ASST performance of stressed and control rats. Since the selective blockade of 5-HT7 receptors has been previously demonstrated to enhance the behavioural effects of antidepressants, the second goal was to examine the impact of the joint administration of inactive doses of SB-269970 and escitalopram in the ASST. SB-269970 (0.3 and 1mg/kg) given to stressed rats 30min before testing reversed the restraint-induced impairment of the extra-dimensional (ED) set-shifting ability. Additionally, SB-269970 (1mg/kg) also improved ED performance of the unstressed control group. Moreover, SB-269970, given at an inactive dose, enhanced the pro-cognitive efficacy of escitalopram. In conclusion, these results highlight the possibility that 5-HT7 receptor antagonism may represent a useful pharmacological approach in the treatment of frontal-like cognitive disturbances in stress-related psychiatric disorders.

  7. Targeted inhibition of serotonin type 7 (5-HT7) receptor function modulates immune responses and reduces the severity of intestinal inflammation.

    PubMed

    Kim, Janice J; Bridle, Byram W; Ghia, Jean-Eric; Wang, Huaqing; Syed, Shahzad N; Manocha, Marcus M; Rengasamy, Palanivel; Shajib, Mohammad Sharif; Wan, Yonghong; Hedlund, Peter B; Khan, Waliul I

    2013-05-01

    Mucosal inflammation in conditions ranging from infective acute enteritis or colitis to inflammatory bowel disease is accompanied by alteration in serotonin (5-hydroxytryptamine [5-HT]) content in the gut. Recently, we have identified an important role of 5-HT in the pathogenesis of experimental colitis. 5-HT type 7 (5-HT7) receptor is one of the most recently identified members of the 5-HT receptor family, and dendritic cells express this receptor. In this study, we investigated the effect of blocking 5-HT7 receptor signaling in experimental colitis with a view to develop an improved therapeutic strategy in intestinal inflammatory disorders. Colitis was induced with dextran sulfate sodium (DSS) or dinitrobenzene sulfonic acid (DNBS) in mice treated with selective 5-HT7 receptor antagonist SB-269970, as well as in mice lacking 5-HT7 receptor (5-HT7(-/-)) and irradiated wild-type mice reconstituted with bone marrow cells harvested from 5-HT7(-/-) mice. Inhibition of 5-HT7 receptor signaling with SB-269970 ameliorated both acute and chronic colitis induced by DSS. Treatment with SB-269970 resulted in lower clinical disease, histological damage, and proinflammatory cytokine levels compared with vehicle-treated mice post-DSS. Colitis severity was significantly lower in 5-HT7(-/-) mice and in mice reconstituted with bone marrow cells from 5-HT7(-/-) mice compared with control mice after DSS colitis. 5-HT7(-/-) mice also had significantly reduced DNBS-induced colitis. These observations provide us with novel information on the critical role of the 5-HT7 receptor in immune response and inflammation in the gut, and highlight the potential benefit of targeting this receptor to alleviate the severity of intestinal inflammatory disorders such as inflammatory bowel disease.

  8. Stimulation of 5-HT7 receptor during adolescence determines its persistent upregulation in adult rat forebrain areas.

    PubMed

    Nativio, Paola; Zoratto, Francesca; Romano, Emilia; Lacivita, Enza; Leopoldo, Marcello; Pascale, Esterina; Passarelli, Francesca; Laviola, Giovanni; Adriani, Walter

    2015-11-01

    Brain serotonin 7 (5-HT7) receptors play an important functional role in learning and memory, in regulation of mood and motivation, and for circadian rhythms. Recently, we have studied the modulatory effects of a developmental exposure (under subchronic regimen) in rats with LP-211, a brain-penetrant and selective 5-HT7 receptor agonist. We aimed at further deciphering long-term sequelae into adulthood. LP-211 (0.250 mg/kg i.p., once/day) was administered for 5 days during the adolescent phase (postnatal days 43-45 to 47-49). When adult (postnatal days >70), forebrain areas were obtained for ex vivo immunohistochemistry, whose results prompted us to reconsider the brain connectivity maps presented in our previous study (Canese et al., Psycho-Pharmacol 2015;232:75-89.) Significant elevation in levels of 5-HT7 receptors were evidenced due to adolescent LP-211 exposure, in dorsal striatum (which also shows an increase of dopaminergic D2 auto-receptors) and-unexpectedly-in piriform cortex, with no changes in ventral striatum. We observed that functional connectivity from a seed on the right hippocampus was more extended than reported, also including the piriform cortex. As a whole, the cortical loop rearranged by adolescent LP-211 exposure consisted in a hippocampus receiving connections from piriform cortex and dorsal striatum, the latter both directly and through functional control over the 'extended amygdala'. Such results represent a starting point to explore neurophysiology of 5-HT7 receptors. Further investigation is warranted to develop therapies for sleep disorders, for impaired emotional and motivational regulation, for attentive and executive deficit. The 5-HT7 agonist LP-211 (0.250 mg/kg i.p., once/day) was administered for 5 days during adolescence (postnatal days 43-45 to 47-49) in rats. When adult (postnatal days >70), a significant elevation in levels of 5-HT7 receptors were evidenced in dorsal striatum and-unexpectedly-in piriform cortex.

  9. ECH tokamak

    SciTech Connect

    Firestone, M.A.; Mau, T.K.; Conn, R.W.

    1985-04-01

    A small steady-state tokamak capable of producing power in the 100 to 300 MWe range and relying on electron cyclotron RF heating (ECH) for both heating and current drive is described. Working in the first MHD stability regime for tokamaks, the approach adheres to the recently discovered maximum beta limit. An appropriate figure of merit is the ratio of the fusion power to absorbed RF power. Efficient devices are feasible at both small and large values of fusion power, thereby pointing to a development path for an attractive commercial fusion reactor.

  10. Human 5–HT4 and 5–HT7 Receptor Splice Variants: Are they Important?

    PubMed Central

    Coupar, Ian M; Desmond, Paul V; Irving, Helen R

    2007-01-01

    G-protein-coupled receptors (GPCRs), which are encoded by >300 genes in the human genome, are by far the largest class of targets for modern drugs. These macromolecules display inherent adaptability of function, which is partly due to the production of different forms of the receptor protein. These are commonly called ‘isoforms’ or ‘splice variants’ denoting the molecular process of their production/assembly. Not all GPCRs are expressed as splice variants, but certain subclasses of 5–HT receptors are for example, the 5–HT4 and 5–HT7 receptors. There are at least 11 human 5–HT4 and three h5–HT7 receptor splice variants. This review describestheir discoveries, nomenclature and structures. The discovery that particular splice variants are tissue specific (or prominent) has highlighted their potential as future drug targets. In particular, this review examines the functional relevance of different 5–HT4 and 5–HT7 receptor splice variants. Examples are given to illustrate that splice variants have differential modulatory influences on signalling processes. Differences in agonist potency and efficacies and also differences in desensitisation rates to 5–HT occur with both 5–HT4 and 5–HT7 receptor splice variants. The known and candidate signalling systems that allow for splice variant specific responses include GPCR interacting proteins (GIPs) and GPCR receptor kinases (GRKs) which are examined.Finally, the relevance of 5–HT receptor splice variants to clinical medicine and to the pharmaceutical industry is discussed. PMID:19305739

  11. The effects of a 5-HT7 receptor agonist and antagonist on morphine withdrawal syndrome in mice.

    PubMed

    Shahidi, Siamak; Hashemi-Firouzi, Nasrin

    2014-08-22

    Withdrawal from opioids leads to the expression of aversion behaviors. Previous studies have shown that the serotonergic system has an important role in morphine withdrawal syndrome. The 5-HT7 receptor is a recently discovered member of the 5-HT receptor family that has been shown to be involved in these behaviors. The aim of the present study was to test the role of the 5-HT7 receptor in withdrawal syndrome in morphine-dependent mice with AS19 and SB269970, a selective agonist and antagonist of this receptor, respectively. Dependence was induced by the repeated administration of morphine for five consecutive days. The morphine-dependent mice received AS19 (3, 5, or 10mg/kg, intraperitoneal) or SB269970 (1, 3, or 10mg/kg, intraperitoneal) 15 min prior to the precipitation of morphine withdrawal syndromes by naloxone (3mg/kg, subcutaneous). Withdrawal symptoms, including percent weight loss, jumping, teeth chattering, writhing, body and face grooming, sniffing, standing, and head and limb shaking, were recorded for 30 min after the naloxone injection. The morphine-dependent mice had significantly more withdrawal symptoms than naive control mice. The administration of AS19 reduced most of the morphine withdrawal symptoms. However, SB2699 increased some of the withdrawal symptoms, including teeth chattering, face grooming, jumping, and head and limb shaking. These findings suggest that the 5-HT7 receptor is involved in morphine withdrawal. Its activation decreased and its inactivation increased the morphine withdrawal syndrome. Further studies are recommended to better understand the role of the 5-HT7 receptor in morphine dependence and withdrawal.

  12. Pharmacological Blockade of Serotonin 5-HT7 Receptor Reverses Working Memory Deficits in Rats by Normalizing Cortical Glutamate Neurotransmission

    PubMed Central

    Bonaventure, Pascal; Aluisio, Leah; Shoblock, James; Boggs, Jamin D.; Fraser, Ian C.; Lord, Brian; Lovenberg, Timothy W.; Galici, Ruggero

    2011-01-01

    The role of 5-HT7 receptor has been demonstrated in various animal models of mood disorders; however its function in cognition remains largely speculative. This study evaluates the effects of SB-269970, a selective 5-HT7 antagonist, in a translational model of working memory deficit and investigates whether it modulates cortical glutamate and/or dopamine neurotransmission in rats. The effect of SB-269970 was evaluated in the delayed non-matching to position task alone or in combination with MK-801, a non-competitive NMDA receptor antagonist, and, in separate experiments, with scopolamine, a non-selective muscarinic antagonist. SB-269970 (10 mg/kg) significantly reversed the deficits induced by MK-801 (0.1 mg/kg) but augmented the deficit induced by scopolamine (0.06 mg/kg). The ability of SB-269970 to modulate MK-801-induced glutamate and dopamine extracellular levels was separately evaluated using biosensor technology and microdialysis in the prefrontal cortex of freely moving rats. SB-269970 normalized MK-801 -induced glutamate but not dopamine extracellular levels in the prefrontal cortex. Rat plasma and brain concentrations of MK-801 were not affected by co-administration of SB-269970, arguing for a pharmacodynamic rather than a pharmacokinetic mechanism. These results indicate that 5-HT7 receptor antagonists might reverse cognitive deficits associated with NMDA receptor hypofunction by selectively normalizing glutamatergic neurotransmission. PMID:21701689

  13. 5-HT7 receptor-mediated fear conditioning and possible involvement of extracellular signal-regulated kinase.

    PubMed

    Takeda, Kotaro; Tsuji, Minoru; Miyagawa, Kazuya; Takeda, Hiroshi

    2017-01-18

    Fear conditioning is a valuable behavioral paradigm for studying the neural basis of emotional learning and memory. The present study examined the involvement of extracellular signal-regulated kinase 1/2 (ERK) signaling on the serotonin (5-HT)7 receptor-mediated fear conditioning. Conditioning was performed in a trial in which a tone was followed by an electrical foot-shock. Context- and tone-dependent fear were examined in tests conducted 24 and 48h after conditioning, respectively. The selective 5-HT7 receptor antagonist 2a-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)butyl]-2a,3,4,-tetrahydrobenzo(c,d)indol-2-(1H)-one (DR4004) (5mg/kg), when administered intraperitoneally (i.p.) immediately after conditioning, caused a significant decrease in both context- and tone-dependent fear responses (freezing behavior). A significant increase in ERK activity was observed in the amygdala of mice that displayed context- or tone-dependent fear responses, and these changes were also inhibited by the administration of DR4004 (5mg/kg, i.p.) immediately after conditioning. In contrast, the increase in hippocampal ERK activity in mice that displayed context-dependent fear responses was further enhanced by the administration of DR4004 (5mg/kg, i.p.). These results suggest that 5-HT7 receptor-mediated ERK signaling may play a significant role in the processes of emotional learning and memory.

  14. 5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

    PubMed Central

    Ciranna, Lucia; Catania, Maria Vincenza

    2014-01-01

    Serotonin type 7 receptors (5-HT7) are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD), including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD. PMID:25221471

  15. 5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders.

    PubMed

    Ciranna, Lucia; Catania, Maria Vincenza

    2014-01-01

    Serotonin type 7 receptors (5-HT7) are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD), including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD.

  16. Functional expression of 5-HT7 receptor on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice.

    PubMed

    Yang, Eun Ju; Han, Seong Kyu; Park, Soo Joung

    2013-10-25

    The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc; medullary dorsal horn) receives and processes orofacial nociceptive inputs, and serotonergic fibers involved in the descending modulation of nociception are more densely distributed in the superficial laminae of the Vc. This study investigated the direct effects of 5-HT1A/7 receptor agonist 8-OH-DPAT on SG neurons of the Vc to assess functional expression of the 5-HT7 receptor using gramicidin-perforated patch-clamp in postnatal day (PND) 5-84 male mice. Of the 70 SG neurons tested, bath application of 8-OH-DPAT (30μM) induced depolarization (n=33), hyperpolarization (n=16) or no response (n=21). In another 10 SG neurons, 8-OH-DPAT in the presence of 5-HT1A receptor antagonist WAY-100635 (1μM) elicited either depolarization (n=6) or no response (n=4); hyperpolarization was not observed. The 8-OH-DPAT-induced depolarization was significantly blocked by the selective 5-HT7 receptor antagonist SB-269970 (10μM; n=8), but not by WAY-100635 (1μM; n=5). The depolarizing effect of 8-OH-DPAT was maintained in the presence of TTX, CNQX, AP5, picrotoxin, and strychnine, indicating direct postsynaptic action of 8-OH-DPAT on SG neurons (n=6). 5-HT7 receptor mRNA was also detected in five of 21 SG neurons by single-cell RT-PCR. The mean amplitude of 8-OH-DPAT-induced depolarization in PND 5-21 mice (n=21) was significantly larger than that in PND 22-84 mice (n=12), although the proportion of SG neurons responding to 8-OH-DPAT by depolarization did not differ significantly between two age groups of mice. These results indicate that 5-HT7 receptors are functionally expressed in a subpopulation of SG neurons of the Vc and activation of 5-HT7 receptors plays an important role in modulating orofacial nociceptive processing in the SG neurons of the Vc.

  17. Downregulation of 5-HT7 Serotonin Receptors by the Atypical Antipsychotics Clozapine and Olanzapine. Role of Motifs in the C-Terminal Domain and Interaction with GASP-1.

    PubMed

    Manfra, Ornella; Van Craenenbroeck, Kathleen; Skieterska, Kamila; Frimurer, Thomas; Schwartz, Thue W; Levy, Finn Olav; Andressen, Kjetil Wessel

    2015-07-15

    The human 5-HT7 serotonin receptor, a G-protein-coupled receptor (GPCR), activates adenylyl cyclase constitutively and upon agonist activation. Biased ligands differentially activate 5-HT7 serotonin receptor desensitization, internalization and degradation in addition to G protein activation. We have previously found that the atypical antipsychotics clozapine and olanzapine inhibited G protein activation and, surprisingly, induced both internalization and lysosomal degradation of 5-HT7 receptors. Here, we aimed to determine the mechanism of clozapine- and olanzapine-mediated degradation of 5-HT7 receptors. In the C-terminus of the 5-HT7 receptor, we identified two YXXΦ motifs, LR residues, and a palmitoylated cysteine anchor as potential sites involved in receptor trafficking to lysosomes followed by receptor degradation. Mutating either of these sites inhibited clozapine- and olanzapine-mediated degradation of 5-HT7 receptors and also interfered with G protein activation. In addition, we tested whether receptor degradation was mediated by the GPCR-associated sorting protein-1 (GASP-1). We show that GASP-1 binds the 5-HT7 receptor and regulates the clozapine-mediated degradation. Mutations of the identified motifs and residues, located in or close to Helix-VIII of the 5-HT7 receptor, modified antipsychotic-stimulated binding of proteins (such as GASP-1), possibly by altering the flexibility of Helix-VIII, and also interfered with G protein activation. Taken together, our data demonstrate that binding of clozapine or olanzapine to the 5-HT7 receptor leads to antagonist-mediated lysosomal degradation by exposing key residues in the C-terminal tail that interact with GASP-1.

  18. Expression and role of 5-HT7 receptor in brain and intestine in rats with irritable bowel syndrome.

    PubMed

    Zou, Bai-cang; Dong, Lei; Wang, Yan; Wang, Sheng-hao; Cao, Ming-bo

    2007-12-05

    The 5-hydroxytryptamine7 receptor (5-HT(7) receptor, 5-HT(7)R) plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome (IBS). The aim of this study was to investigate the role of the 5-HT(7) receptor in the pathogenesis of IBS. A rat model of irritable bowel syndrome with diarrhea (IBS-D) was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation (IBS-C) was established by stomach irrigated with 0 - 4 degrees C cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT(7) receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate (cAMP) in all the same tissues was measured by radioimmunity. The models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon (P < 0.05), as well as more than were found in the IBS-C group in jejunum and ileum (P < 0.05). There were more 5-HT positive cells in the IBS-C group than in the control hippocampus, hypothalamus, ileum, proximate colon, and distal colon (P < 0.05). Real time-PCR results showed that the expression level of the 5-HT(7) receptor in both the IBS-C and IBS-D groups were enhanced compared with the control group in the hippocampus and hypothalamus (P < 0.05). The expression level of 5-HT(7) receptors in the IBS-C group was notably greater when compared with the controls in the ileum and colon (P < 0.05). The cAMP accumulation in the hippocampus and hypothalamus in

  19. Clozapine and other competitive antagonists reactivate risperidone-inactivated h5-HT7 receptors: radioligand binding and functional evidence for GPCR homodimer protomer interactions

    PubMed Central

    Toohey, Nicole; Knight, Jessica A.; Klein, Michael T.; Smith, Carol

    2011-01-01

    Rationale The h5-HT7 receptor is subject to inactivation by risperidone and 9-OH-risperidone, apparently through a pseudo-irreversible complex formed between these drugs and the receptor. Although risperidone and 9-OH-risperidone (“inactivating antagonists”) completely inactivate the receptor, only 50% of the receptors form a pseudo-irreversible complex with these drugs. Objectives This study aims to more fully determine the mechanism(s) responsible for the novel effects of risperidone and 9-OH-risperidone and to determine if the inactivation can be reversed (reactivation). Methods The ability of non-inactivating drugs (competitive antagonists) to dissociate wash-resistant [3H]risperidone binding from h5-HT7 receptors was investigated. Also, the ability of non-inactivating drugs to reactivate inactivated h5-HT7 receptors was investigated, using cAMP accumulation as a functional endpoint. Results The competitive (non-inactivating) antagonists clozapine and mesulergine released the wash-resistant [3H]risperidone binding to the h5-HT7 receptor. The competitive antagonists clozapine, SB269970, mianserin, cyproheptadine, mesulergine, and ICI169369 reactivated the risperidone-inactivated h5-HT7 receptors in a concentration-dependent manner. The potencies for reactivation closely match the affinities of these drugs for the h5-HT7 receptor (r2=0.95), indicating that the reactivating antagonists are binding to and producing their effects through the orthosteric binding site of the h5-HT7 receptor. Bioluminescence resonance energy transfer analyses indicate that the h5-HT7 receptor forms homodimers. Conclusions The ability of the non-inactivating drugs to bind h5-HT7 orthosteric sites and reverse the wash-resistant effects of risperidone or 9-OH-risperidone, also bound to h5-HT7 orthosteric sites, is evidence for protomer–protomer interactions between h5-HT7 homodimers. This is the first demonstration of a non-mutated G-protein-coupled receptor homodimer engaging in

  20. Corticosterone induced morphological changes of hippocampal and amygdaloid cell lines are dependent on 5-HT7 receptor related signal pathway.

    PubMed

    Xu, Y; Zhang, C; Wang, R; Govindarajan, S S; Barish, P A; Vernon, M M; Fu, C; Acharya, A P; Chen, L; Boykin, E; Yu, J; Pan, J; O'Donnell, J M; Ogle, W O

    2011-05-19

    Stress is an unavoidable life experience. It induces mood, cognitive dysfunction and plasticity changes in chronically stressed individuals. Among the various brain regions that have been studied, the hippocampus and amygdala have been observed to have different roles in controlling the limbic-hypothalamic-pituitary-adrenal axis (limbic-HPA axis). This study investigated how the stress hormone corticosterone (CORT) affects neuronal cells. The first aim is to test whether administration of CORT to hippocampal and amygdaloid cell lines induces different changes in the 5-HT receptor subtypes. The second goal is to determine whether stress induced morphological changes in these two cell lines were involved in the 5-HT receptor subtypes expression. We now show that 5-HT(7) receptor mRNA levels were significantly upregulated in HT-22 cells, but downregulated in AR-5 cells by exposure to a physiologically relevant level of CORT (50 μM) for 24 h, which was later confirmed by primary hippocampal and amygdaloid neuron cultures. Additionally, pretreatment of cells with 5-HT(7) antagonist SB-269970 or agonist LP-44 reversed CORT induced cell lesion in a dose-dependent manner. Moreover, CORT induced different changes in neurite length, number of neurites and soma size in HT-22 and AR-5 cells were also reversed by pretreatment with either SB-269970 or LP-44. The different effects of 5-HT(7) receptors on cell lines were observed in two members of the Rho family small GTPase expression: the Cdc-42 and RhoA. These observed results support the hypothesis that 5-HT may differentially modulate neuronal morphology in the hippocampus and amygdala depending on the expression levels of the 5-HT receptor subtypes during stress hormone insults.

  1. Effect of 5-HT7 receptor agonist, LP-211, on micturition following spinal cord injury in male rats

    PubMed Central

    Norouzi-Javidan, Abbas; Javanbakht, Javad; Barati, Fardin; Fakhraei, Nahid; Mohammadi, Fatemeh; Dehpour, Ahmad Reza

    2016-01-01

    Background and Purpose: Central and peripheral 5-hydroxytryptamine (5-HT) receptors play a critical role in regulation of micturition reflex. The aim of this study was to evaluate effect of a 5-HT7 receptor agonist, LP-211 (N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide) on micturition reflex in acute spinal cord-injured (SCI) rats during infusion of vehicle into the bladder. Methods: SCI was induced by compressing T10 segment using an aneurysm clip, extradurally in male rats. Following two weeks, LP-211 doses (0.003-0.3 mg/kg) were administered cumulatively (intraperitoneally, i.p.) with 20 min interval. The 5-HT7 antagonist, SB-269970 ((R)-3-[2-[2-(4-Methylpiperidin-1-yl) ethyl] pyrrolidine-1-sulfonyl] phenol hydrochloride), was administered after achievement of LP-211 dose-response. A cystometric study was performed 2 weeks after spinal crushing in all the animals. Cystometric variables consisting of micturition volume (voided volume), residual volume (volume remaining in the bladder after voiding), and bladder capacity (micturition volume plus residual volume). Voiding efficiency was calculated as the percent of micturition volume to bladder capacity. Findings: Intact and sham-operated rats showed few significant changes in micturition reflex. SCI rats responded to LP-211 (0.003-0.3, mg/kg, i.v.) with dose-dependent increases in bladder capacity, and residual volume. In this treatment group, LP-211 induced significant dose-dependent increases in micturition volume, resulting in significant increases in voiding efficiency (P<0.001) compared to intact and sham-operated rats, SB-269970 (0.1 mg/kg, i.v.) completely reversed the LP-211-induced changes on micturition volume and voiding efficiency was decreased significantly. Conclusion: The 5-HT7 receptors activation by LP-211 facilitated the micturition reflex. Furthermore, 5-HT7 receptors do seem to play an important role in physiological regulation of micturition, and as a result, may represent a

  2. Selective 5-HT7 receptor agonists LP 44 and LP 211 elicit an analgesic effect on formalin-induced orofacial pain in mice

    PubMed Central

    DEMİRKAYA, Kadriye; AKGÜN, Özlem Martı; ŞENEL, Buğra; ÖNCEL TORUN, Zeynep; SEYREK, Melik; LACİVİTA, Enza; LEOPOLDO, Marcello; DOĞRUL, Ahmet

    2016-01-01

    ABSTRACT The most recently identified serotonin (5-HT) receptor is the 5-HT7 receptor. The antinociceptive effects of a 5-HT7 receptor agonist have been shown in neuropathic and inflammatory animal models of pain. A recent study demonstrated the functional expression of 5-HT7 receptors in the substantia gelatinosa (SG) of the trigeminal subnucleus caudalis, which receives and processes orofacial nociceptive inputs. Objective To investigate the antinociceptive effects of pharmacological activation of 5-HT7 receptors on orofacial pain in mice. Material and Methods Nociception was evaluated by using an orofacial formalin test in male Balb-C mice. Selective 5-HT7 receptor agonists, LP 44 and LP 211 (1, 5, and 10 mg/kg), were given intraperitoneally 30 min prior to a formalin injection. A bolus of 10 µl of 4% subcutaneous formalin was injected into the upper lip of mice and facial grooming behaviors were monitored. The behavioral responses consisted of two distinct periods, the early phase corresponding to acute pain (Phase I: 0–12 min) and the late phase (Phase II: 12–30 min). Results LP 44 and LP 211 (1, 5, and 10 mg/kg) produced an analgesic effect with reductions in face rubbing time in both Phase I and Phase II of the formalin test. Conclusion Our results suggest that 5-HT7 receptor agonists may be promising analgesic drugs in the treatment of orofacial pain. PMID:27383702

  3. Synthesis and evaluation of 1-[2-(4-[(11)C]methoxyphenyl)phenyl]piperazine for imaging of the serotonin 5-HT7 receptor in the rat brain.

    PubMed

    Shimoda, Yoko; Yui, Joji; Xie, Lin; Fujinaga, Masayuki; Yamasaki, Tomoteru; Ogawa, Masanao; Nengaki, Nobuki; Kumata, Katsushi; Hatori, Akiko; Kawamura, Kazunori; Zhang, Ming-Rong

    2013-09-01

    1-[2-(4-Methoxyphenyl)phenyl]piperazine (4) is a potent serotonin 5-HT7 receptor antagonist (Ki=2.6nM) with a low binding affinity for the 5-HT1A receptor (Ki=476nM). As a potential positron emission tomography (PET) radiotracer for the 5-HT7 receptor, [(11)C]4 was synthesized at high radiochemical yield and specific activity, by O-[(11)C]methylation of 2'-(piperazin-1-yl)-[1,1'-biphenyl]-4-ol (6) with [(11)C]methyl iodide. Autoradiography revealed that [(11)C]4 showed in vitro specific binding with 5-HT7 in the rat brain regions, such as the thalamus which is a region with high 5-HT7 expression. Metabolite analysis indicated that intact [(11)C]4 in the brain exceeded 90% of the radioactive components at 15min after the radiotracer injection, although two radiolabeled metabolites were found in the rat plasma. The PET study of rats showed moderated uptake of [(11)C]4 in the brain (1.2SUV), but no significant regional difference in radioactivity in the brain. Pretreatment with 5-HT7-selective antagonist SB269970 (3) did not decrease the uptake of [(11)C]4 in the rat brain. Further studies are warranted that focus on the development of PET ligand candidates with higher binding affinity for 5-HT7 and higher in vivo stability in brain than 4.

  4. Peripheral 5-HT1A and 5-HT7 Serotonergic Receptors Modulate Parasympathetic Neurotransmission in Long-Term Diabetic Rats

    PubMed Central

    Restrepo, Beatriz; Martín, María Luisa; San Román, Luis; Morán, Asunción

    2010-01-01

    We analyzed the modulation of serotonin on the bradycardia induced in vivo by vagal electrical stimulation in alloxan-induced long-term diabetic rats. Bolus intravenous administration of serotonin had a dual effect on the bradycardia induced either by vagal stimulation or exogenous Ach, increasing it at low doses and decreasing it at high doses of 5-hydroxytryptamine (5-HT), effect reproduced by 5-carboxamidotryptamine maleate (5-CT), a 5-HT1/7 agonist. The enhancement of the bradycardia at low doses of 5-CT was reproduced by 5-HT1A agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) and abolished by WAY-100,635, 5-HT1A antagonist. Pretreatment with 5-HT1 antagonist methiothepin blocked the stimulatory and inhibitory effect of 5-CT, whereas pimozide, 5-HT7 antagonist, only abolished 5-CT inhibitory action. In conclusion, long-term diabetes elicits changes in the subtype of the 5-HT receptor involved in modulation of vagally induced bradycardia. Activation of the 5-HT1A receptors induces enhancement, whereas attenuation is due to 5-HT7 receptor activation. This 5-HT dual effect occurs at pre- and postjunctional levels. PMID:21403818

  5. In the search for a lead structure among series of potent and selective hydantoin 5-HT7 R agents: The drug-likeness in vitro study.

    PubMed

    Latacz, Gniewomir; Lubelska, Annamaria; Jastrzębska-Więsek, Magdalena; Partyka, Anna; Sobiło, Andrzej; Olejarz, Agnieszka; Kucwaj-Brysz, Katarzyna; Satała, Grzegorz; Bojarski, Andrzej J; Wesołowska, Anna; Kieć-Kononowicz, Katarzyna; Handzlik, Jadwiga

    2017-09-08

    Since the year 1993, when 5-HT7 receptor (5-HT7 R) was discovered, there is no selective 5-HT7 R ligand introduced to the pharmaceutical market. One out of the main reasons disqualifying the 5-HT7 R ligands is weak drugability properties, including metabolic instability or low permeability. This study is focused on the search of a lead compound by "drug-likeness" estimation of the first series of selective and potent 5-HT7 R ligands among 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-aryl-piperazin-1-yl)propyl)-5-methylimidazolidine-2,4-dione derivatives (11-16). The most important drugability parameters, i.e., permeability, metabolic stability, and safety, have been evaluated. The main metabolic pathways were determined. The forced swim test (FST) in mice was performed as a primary in vivo assay for compound 13 and the reference 2. The experiments showed promising drug-like properties for all ligands, with special attention to the benzhydryl (diphenylmethyl) derivative 13. The studies have also indicated in vivo activity of the compound 13 that was observed as a significant and specific antidepressant-like activity in the FST. Taking into account the beneficial properties of 13, i.e., good drug-like parameters, the significant antagonistic action, high selectivity to 5-HT7 R, and its in vivo antidepressant-like activity, the compound should be considered as a new lead in the search for drugs acting on CNS via 5-HT7 receptor. © 2017 John Wiley & Sons A/S.

  6. Effects of acupuncture at HT7 on glucose metabolism in a rat model of Alzheimer's disease: an 18F-FDG-PET study

    PubMed Central

    Lai, Xinsheng; Ren, Jie; Lu, Yangjia; Cui, Shaoyang; Chen, Junqi; Huang, Yong; Tang, Chunzhi; Shan, Baoci; Nie, Bingbing

    2016-01-01

    Objective To explore the effects of acupuncture at HT7 on different cerebral regions in a rat model of Alzheimer's disease (AD) with the application of 18F-2-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET). Methods Sixty Wistar rats were included after undergoing a Y-maze electric sensitivity test. Ten rats were used as a healthy control group. The remaining 50 rats were injected stereotaxically with ibotenic acid into the right nucleus basalis magnocellularis and injected intraperitoneally with D-galactose. AD was successfully modelled in 36 rats, which were randomly divided into three groups (n=12 each): the AD group, which remained untreated; the AD+HT7 group, which received 20 sessions of acupuncture at HT7 over 1 month; and the AD+Sham group, which received acupuncture at a distant non-acupuncture point. Total reaction time (TRT) was measured by Y-maze and 18F-FDG-PET scans were conducted on day 1 and 30. PET images were processed with Statistical Parametric Mapping 8.0. Results Pre-treatment, TRT was greater in all AD groups versus controls (mean±SD 24.10±2.48 vs 41.34±5.00 s). Post-treatment, TRT was shortened in AD+HT7 versus AD+Sham and AD groups (p<0.0001, two-way analysis of variance). Glucose metabolic activity in the hippocampus, thalamus, hypothalamus, frontal lobe, and temporal lobe was decreased in AD rats compared with healthy controls and relatively elevated after HT7 acupuncture. Compared with sham acupuncture, HT7 needling had a greater positive influence on brain glucose metabolism. Conclusions Needling at HT7 can improve memory ability and cerebral glucose metabolic activity of the hippocampus, thalamus, hypothalamus, and frontal/temporal lobes in an AD rat model. PMID:26654890

  7. Autoradiographic distribution of 5-HT7 receptors in the human brain using [3H]mesulergine: comparison to other mammalian species

    PubMed Central

    Martín-Cora, Francisco J; Pazos, Angel

    2003-01-01

    The main aim of this investigation was to delineate the distribution of the 5-HT7 receptor in human brain. Autoradiographic studies in guinea-pig and rat brain were also carried out in order to revisit and compare the anatomical distribution of 5-HT7 receptors in different mammalian species.Binding studies were performed in rat frontal cortex membranes using 10 nM [3H]mesulergine in the presence of raclopride (10 μM) and DOI (0.8 μM). Under these conditions, a binding site with pharmacological characteristics consistent with those of the 5-HT7 receptors was identified (rank order of binding affinity values: 5-CT>5-HT>5-MeOT>mesulergine ≈methiothepin>8-OH-DPAT=spiperone ≈(+)-butaclamol≫imipramine ≈(±)-pindolol≫ondansetron ≈clonidine ≈prazosin).The autoradiographic studies revealed that the anatomical distribution of 5-HT7 receptors throughout the human brain was heterogenous. High densities were found over the caudate and putamen nuclei, the pyramidal layer of the CA2 field of the hippocampus, the centromedial thalamic nucleus, and the dorsal raphe nucleus. The inner layer of the frontal cortex, the dentate gyrus of the hippocampus, the subthalamic nucleus and superior colliculus, among others, presented intermediate concentrations of 5-HT7 receptors. A similar brain anatomical distribution of 5-HT7 receptors was observed in all three mammalian species studied.By using [3H]mesulergine, we have mapped for the first time the anatomical distribution of 5-HT7 receptors in the human brain, overcoming the limitations previously found in radiometric studies with other radioligands, and also revisiting the distribution in guinea-pig and rat brain. PMID:14656806

  8. The role of 5-HT7 receptor antagonism in the amelioration of MK-801-induced learning and memory deficits by the novel atypical antipsychotic drug lurasidone.

    PubMed

    Horisawa, Tomoko; Nishikawa, Hiroyuki; Toma, Satoko; Ikeda, Atsushi; Horiguchi, Masakuni; Ono, Michiko; Ishiyama, Takeo; Taiji, Mutsuo

    2013-05-01

    Lurasidone is a novel atypical antipsychotic with high affinity for dopamine D2, serotonin 5-HT7 and 5-HT2A receptors. We previously reported that lurasidone and the selective 5-HT7 receptor antagonist, SB-656104-A improved learning and memory deficits induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, in the rat passive avoidance test. In this study, we first examined the role of the 5-HT7 receptor antagonistic activity of lurasidone in its pro-cognitive effect to ameliorate MK-801-induced deficits in the rat passive avoidance test. The 5-HT7 receptor agonist, AS19, (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino) tetralin, (3 mg/kg, s.c.) completely blocked the attenuating effects of lurasidone (3 mg/kg, p.o.), highlighting the importance of 5-HT7 receptor antagonism in the pro-cognitive effect of lurasidone. AS19 (3 mg/kg, s.c.) also blocked the ameliorating effect of SB-656104-A (10 mg/kg, i.p.) in the same experimental paradigm. To further extend our observation, we next tested whether 5-HT7 receptor antagonism still led to the amelioration of MK-801-induced deficits when combined with D2 and 5-HT2A receptor antagonists, and found that SB-656104-A (10 mg/kg, i.p.) significantly ameliorated MK-801-induced deficits even in the presence of the D2 receptor antagonist raclopride (0.1 mg/kg, s.c.) and 5-HT2A receptor antagonist ketanserin (1 mg/kg, s.c.). Taken together, these results suggest that the 5-HT7 receptor antagonistic activity of lurasidone plays an important role in its effectiveness against MK-801-induced deficits, and may contribute to its pharmacological actions in patients with schizophrenia.

  9. Laser Acupuncture at HT7 Acupoint Improves Cognitive Deficit, Neuronal Loss, Oxidative Stress, and Functions of Cholinergic and Dopaminergic Systems in Animal Model of Parkinson's Disease.

    PubMed

    Wattanathorn, Jintanaporn; Sutalangka, Chatchada

    2014-01-01

    To date, the therapeutic strategy against cognitive impairment in Parkinson's disease (PD) is still not in satisfaction level and requires novel effective intervention. Based the oxidative stress reduction and cognitive enhancement induced by laser acupuncture at HT7, the beneficial effect of laser acupuncture at HT7 against cognitive impairment in PD has been focused. In this study, we aimed to determine the effect of laser acupuncture at HT7 on memory impairment, oxidative stress status, and the functions of both cholinergic and dopaminergic systems in hippocampus of animal model of PD. Male Wistar rats, weighing 180-220 g, were induced unilateral lesion at right substantianigra by 6-OHDA and were treated with laser acupuncture continuously at a period of 14 days. The results showed that laser acupuncture at HT7 enhanced memory and neuron density in CA3 and dentate gyrus. The decreased AChE, MAO-B, and MDA together with increased GSH-Px in hippocampus of a 6-OHDA lesion rats were also observed. In conclusion, laser acupuncture at HT7 can improve neuron degeneration and memory impairment in animal model of PD partly via the decreased oxidative stress and the improved cholinergic and dopaminergic functions. More researches concerning effect of treatment duration are still required.

  10. Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats.

    PubMed

    Lin, Hai; Heo, Bong Ha; Kim, Woong Mo; Kim, Yong Chul; Yoon, Myung Ha

    2015-06-26

    Although tianeptine, an atypical antidepressant has been reported to have antinociceptive effects, the mode of action is different from that of tricyclic antidepressants despite structural similarities. We examined the antiallodynic effect of intrathecal tianeptine in neuropathic pain rats and determined the involvement of 5-hydroxytryptamine type 7 (5-HT7) receptor of the GABAergic interneurons in the spinal cord. Neuropathic pain was induced by spinal nerve ligation (SNL). After observation of the effect from intrathecal tianeptine, a 5-HT7 receptor antagonist (SB-269970) was administered intrathecally 10 min before delivery of tianeptine, to determine the contribution of spinal 5-HT7 receptor on the activity of tianeptine. GAD expression and GABA concentrations were assessed. Intrathecal tianeptine dose-dependently attenuated mechanical allodynia in SNL rats. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of tianeptine. Both GAD65 expression and the GABA concentration in the spinal cord were decreased in neuropathic rats but were increased by tianeptine. Additionally, 5-HT7 receptor and GAD65 were co-localized in the spinal cord. Intrathecal tianeptine reduces neuropathic pain. 5-HT7 receptor of the GABAergic interneurons together with GAD65 plays a role in the activity of tianeptine at the spinal cord level.

  11. Effects of the selective 5-HT7 receptor antagonist SB-269970 and amisulpride on ketamine-induced schizophrenia-like deficits in rats.

    PubMed

    Nikiforuk, Agnieszka; Kos, Tomasz; Fijał, Katarzyna; Hołuj, Małgorzata; Rafa, Dominik; Popik, Piotr

    2013-01-01

    A wide body of evidence suggests that 5-HT7 receptors are implicated in a variety of central nervous system functions, including control of learning and memory processes. According to recent preclinical data, the selective blockade of these receptors may be a potential target for cognitive improvement in schizophrenia. The first aim of the present study was to evaluate the effects of the selective 5-HT7 receptor antagonist, SB-269970, and the antipsychotic drug with a high affinity for 5-HT7 receptors, amisulpride, on ketamine-induced deficits in attentional set-shifting and novel object recognition tasks in rats. Because the role of 5-HT7 receptor blockade in ameliorating positive and negative symptoms of schizophrenia remains equivocal, the second aim of these experiments was to examine the effectiveness of SB-269970 and amisulpride in reversing ketamine-induced deficits in prepulse inhibition of the startle reflex and in social interaction test in rats. The study revealed that acute administration of SB-269970 (1 mg/kg) or amisulpride (3 mg/kg) ameliorated ketamine-induced cognitive inflexibility and novel object recognition deficit in rats. Both compounds were also effective in attenuating ketamine-evoked disruption of social interactions. In contrast, neither SB-269970 nor amisulpride affected ketamine-disrupted prepulse inhibition or 50 kHz USVs accompanying social behaviour. In conclusion, antagonism of 5-HT7 receptors may represent a useful pharmacological approach in the treatment of cognitive deficits and some negative symptoms of schizophrenia.

  12. [CROSS-TALK BETWEEN 5-HT1A AND 5-HT7 RECEPTORS: ROLE IN THE AUTOREGULATION OF THE BRAIN SEROTONIN SYSTEM AND IN MECHANISM OF ANTIDEPRESSANTS ACTION].

    PubMed

    Popova, N K; Ponimaskin, E G; Naumenko, V S

    2015-11-01

    Recent studies considerably extended our knowledge of the mechanisms and physiological role of the interaction between different receptors in the brain. Current review summarizes data on the formation of receptor complexes and the role of such complexes in the autoregulation of the brain serotonin system, behavioral abnormalities and mechanism of antidepressants action. Particular attention is paid to 5-HT1A and 5-HT7 receptor heterodimers. The results described in the present review indicate that: i) dimerization and formation of mobile receptor complexes is a common feature for the members of G-protein coupled receptor superfamily; ii) 5-HT7 receptor appears to be a modulator for 5-HT1A receptor - the key autoregulator of the brain serotonin system; iii) 5-HT1A/5-HT7 receptor complexes formation is one of the mechanisms for inactivation and desensitization of the 5-HTIA receptors in the brain; iv) differences in the 5-HT7 receptor and 5-HTIA/5-HT7 heterodimers density define different sensitivity of pre- and postsynaptic 5-HTlA receptors to chronic treatment with selective serotonin reuptake inhibitors.

  13. Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity

    PubMed Central

    Shelton, Jonathan; Yun, Sujin; Losee Olson, Susan; Turek, Fred; Bonaventure, Pascal; Dvorak, Curt; Lovenberg, Timothy; Dugovic, Christine

    2015-01-01

    Recent reports have illustrated a reciprocal relationship between circadian rhythm disruption and mood disorders. The 5-HT7 receptor may provide a crucial link between the two sides of this equation since the receptor plays a critical role in sleep, depression, and circadian rhythm regulation. To further define the role of the 5-HT7 receptor as a potential pharmacotherapy to correct circadian rhythm disruptions, the current study utilized the selective 5-HT7 antagonist JNJ-18038683 (10 mg/kg) in three different circadian paradigms. While JNJ-18038683 was ineffective at phase shifting the onset of wheel running activity in mice when administered at different circadian time (CT) points across the circadian cycle, pretreatment with JNJ-18038683 blocked non-photic phase advance (CT6) induced by the 5-HT1A/7 receptor agonist 8-OH-DPAT (3 mg/kg). Since light induced phase shifts in mammals are partially mediated via the modulation of the serotonergic system, we determined if JNJ-18038683 altered phase shifts induced by a light pulse at times known to phase delay (CT15) or advance (CT22) wheel running activity in free running mice. Light exposure resulted in a robust shift in the onset of activity in vehicle treated animals at both times tested. Administration of JNJ-18038683 significantly attenuated the light induced phase delay and completely blocked the phase advance. The current study demonstrates that pharmacological blockade of the 5-HT7 receptor by JNJ-18038683 blunts both non-photic and photic phase shifts of circadian wheel running activity in mice. These findings highlight the importance of the 5-HT7 receptor in modulating circadian rhythms. Due to the opposite modulating effects of light resetting between diurnal and nocturnal species, pharmacotherapy targeting the 5-HT7 receptor in conjunction with bright light therapy may prove therapeutically beneficial by correcting the desynchronization of internal rhythms observed in depressed individuals. PMID:25642174

  14. The effects of the 5-HT(6) receptor agonist EMD and the 5-HT(7) receptor agonist AS19 on memory formation.

    PubMed

    Meneses, A; Perez-Garcia, G; Liy-Salmeron, G; Flores-Galvez, D; Castillo, C; Castillo, E

    2008-12-16

    Growing evidence indicates that 5-hydrohytryptamine (5-HT) receptors mediate learning and memory. Particularly interesting are 5-HT(6) and 5-HT(7) receptors, which are localized in brain areas involved in memory formation. Interestingly, recently selective 5-HT(6) and 5-HT(7) receptor agonists and antagonists have become available. Previous evidence indicates that 5-HT(6) or 5-HT(7) receptors antagonists had no effects, improved memory formation and/or reversed amnesia. Herein, the effects of EMD (a 5-HT(6) receptor agonist) and AS19 (a 5-HT(7) receptor agonist) in the associative learning task of autoshaping were studied. Post-training systemic administration of EMD (1-10 mg/kg) or AS19 (1-10 mg/kg) were tested in short-term memory (STM) and long-term memory (LTM). Results showed that only EMD 5.0mg/kg impaired both STM and LTM. AS19 at 1-10 mg/kg significantly impaired STM but not LTM. In those groups used to test only LTM, EMD impaired it; while AS19 improved LTM. Moreover, in the interaction experiments, the STM EMD-impairment effect was partially reversed by the selective 5-HT(6) receptor antagonist SB-399885 (10 mg/kg). The STM AS19-impairment effect (5.0 mg/kg) was not altered by the selective 5-HT(1A) antagonist WAY 100635 (0.3 mg/kg) but reversed by the selective 5-HT(7) receptor antagonist SB-269970 (10.0 mg/kg). The AS19-SB-269970 combination impaired LTM. Taken together these data suggest that the stimulation of 5-HT(6) impaired both STM and LTM. 5-HT(7) receptors stimulation impaired STM but improved LTM. And these results are discussed in the context of their possible neural bases.

  15. Human 5-HT7 receptor-induced inactivation of forskolin-stimulated adenylate cyclase by risperidone, 9-OH-risperidone and other "inactivating antagonists".

    PubMed

    Toohey, Nicole; Klein, Michael T; Knight, Jessica; Smith, Carol; Teitler, Milt

    2009-09-01

    We have previously reported on the unusual human 5-hydroxytryptamine(7) (h5-HT(7)) receptor-inactivating properties of risperidone, 9-OH-risperidone, bromocriptine, methiothepin, metergoline, and lisuride. Inactivation was defined as the inability of 10 microM 5-HT to stimulate cAMP accumulation after brief exposure and thorough removal of the drugs from HEK293 cells expressing h5-HT(7) receptors. Herein we report that brief exposure of the h5-HT(7) receptor-expressing cells to inactivating drugs, followed by removal of the drugs, results in potent and efficacious irreversible inhibition of forskolin-stimulated adenylate cyclase activity. Pretreatment, followed by removal of the inactivating drugs inhibited 10 microM forskolin-stimulated adenylate cyclase activity with potencies similar to the drugs' affinities for the h5-HT(7) receptor. The actions of the inactivating drugs were pertussis toxin-insensitive, indicating the lack of G(i) in their mechanism(s) of action. Methiothepin and bromocriptine maximally inhibited 10 microM forskolin-stimulated adenylate cyclase, whereas the other drugs produced partial inhibition, indicating the drugs are inducing slightly different inactive conformations of the h5-HT(7) receptor. Maximal effects of these inactivating drugs occurred within 15 to 30 min of exposure of the cells to the drugs. A G(s)-mediated inhibition of forskolin-stimulated activity has never been reported. The inactivating antagonists seem to induce a stable conformation of the h5-HT(7) receptor, which induces an altered state of G(s), which, in turn, inhibits forskolin-mediated stimulation of adenylate cyclase. These and previous observations indicate that the inactivating antagonists represent a unique class of drugs and may reveal GPCR regulatory mechanisms previously unknown. These drugs may produce innovative approaches to the development of therapeutic drugs.

  16. Antinociception by systemically-administered acetaminophen (paracetamol) involves spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors.

    PubMed

    Liu, Jean; Reid, Allison R; Sawynok, Jana

    2013-03-01

    Acetaminophen (paracetamol) is a widely used analgesic, but its sites and mechanisms of action remain incompletely understood. Recent studies have separately implicated spinal adenosine A(1) receptors (A(1)Rs) and serotonin 5-HT(7) receptors (5-HT(7)Rs) in the antinociceptive effects of systemically administered acetaminophen. In the present study, we determined whether these two actions are linked by delivering a selective 5-HT(7)R antagonist to the spinal cord of mice and examining nociception using the formalin 2% model. In normal and A(1)R wild type mice, antinociception by systemic (i.p.) acetaminophen 300mg/kg was reduced by intrathecal (i.t.) delivery of the selective 5-HT(7)R antagonist SB269970 3μg. In mice lacking A(1)Rs, i.t. SB269970 did not reverse antinociception by systemic acetaminophen, indicating a link between spinal 5-HT(7)R and A(1)R mechanisms. We also explored potential roles of peripheral A(1)Rs in antinociception by acetaminophen administered both locally and systemically. In normal mice, intraplantar (i.pl.) acetaminophen 200μg produced antinociception in the formalin test, and this was blocked by co-administration of the selective A(1)R antagonist DPCPX 4.5μg. Acetaminophen administered into the contralateral hindpaw had no effect, indicating a local peripheral action. When acetaminophen was administered systemically, its antinociceptive effect was reversed by i.pl. DPCPX in normal mice; this was also observed in A(1)R wild type mice, but not in those lacking A(1)Rs. In summary, we demonstrate a link between spinal 5-HT(7)Rs and A(1)Rs in the spinal cord relevant to antinociception by systemic acetaminophen. Furthermore, we implicate peripheral A(1)Rs in the antinociceptive effects of locally- and systemically-administered acetaminophen.

  17. Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity.

    PubMed

    Shelton, Jonathan; Yun, Sujin; Losee Olson, Susan; Turek, Fred; Bonaventure, Pascal; Dvorak, Curt; Lovenberg, Timothy; Dugovic, Christine

    2014-01-01

    Recent reports have illustrated a reciprocal relationship between circadian rhythm disruption and mood disorders. The 5-HT7 receptor may provide a crucial link between the two sides of this equation since the receptor plays a critical role in sleep, depression, and circadian rhythm regulation. To further define the role of the 5-HT7 receptor as a potential pharmacotherapy to correct circadian rhythm disruptions, the current study utilized the selective 5-HT7 antagonist JNJ-18038683 (10 mg/kg) in three different circadian paradigms. While JNJ-18038683 was ineffective at phase shifting the onset of wheel running activity in mice when administered at different circadian time (CT) points across the circadian cycle, pretreatment with JNJ-18038683 blocked non-photic phase advance (CT6) induced by the 5-HT1A/7 receptor agonist 8-OH-DPAT (3 mg/kg). Since light induced phase shifts in mammals are partially mediated via the modulation of the serotonergic system, we determined if JNJ-18038683 altered phase shifts induced by a light pulse at times known to phase delay (CT15) or advance (CT22) wheel running activity in free running mice. Light exposure resulted in a robust shift in the onset of activity in vehicle treated animals at both times tested. Administration of JNJ-18038683 significantly attenuated the light induced phase delay and completely blocked the phase advance. The current study demonstrates that pharmacological blockade of the 5-HT7 receptor by JNJ-18038683 blunts both non-photic and photic phase shifts of circadian wheel running activity in mice. These findings highlight the importance of the 5-HT7 receptor in modulating circadian rhythms. Due to the opposite modulating effects of light resetting between diurnal and nocturnal species, pharmacotherapy targeting the 5-HT7 receptor in conjunction with bright light therapy may prove therapeutically beneficial by correcting the desynchronization of internal rhythms observed in depressed individuals.

  18. On the role of brain 5-HT7 receptor in the mechanism of hypothermia: comparison with hypothermia mediated via 5-HT1A and 5-HT3 receptor.

    PubMed

    Naumenko, Vladimir S; Kondaurova, Elena M; Popova, Nina K

    2011-12-01

    Intracerebroventricular administration of selective agonist of serotonin 5-HT(7) receptor LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-pyperasinehexanamide hydrochloride; 10.3, 20.5 or 41.0 nmol) produced considerable hypothermic response in CBA/Lac mice. LP44-induced (20.5 nmol) hypothermia was significantly attenuated by the selective 5-HT(7) receptor antagonist SB 269970 (16.1 fmol, i.c.v.) pretreatment. At the same time, intraperitoneal administration of LP44 in a wide range of doses 1.0, 2.0 or 10.0 mg/kg (2.0, 4.0, 20.0 μmol/kg) did not cause considerable hypothermic response. These findings indicate the implication of central, rather than peripheral 5-HT(7) receptors in the regulation of hypothermia. The comparison of LP44-induced (20.5 nmol) hypothermic reaction in eight inbred mouse strains (DBA/2J, CBA/Lac, C57BL/6, BALB/c, ICR, AKR/J, C3H and Asn) was performed and a significant effect of genotype was found. In the same eight mouse strains, functional activity of 5-HT(1A) and 5-HT(3) receptors was studied. The comparison of hypothermic responses produced by 5-HT(7) receptor agonist LP44 (20.5 nmol, i.c.v.) and 5-HT(1A) receptor agonist 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg), 5-HT(3) receptor agonist m-CPBG (40.0 nmol, i.c.v.) did not reveal considerable interstrain correlations between 5-HT(7) and 5-HT(1A) or 5-HT(3) receptor-induced hypothermia. The selective 5-HT(7) receptor antagonist SB 269970 (16.1 fmol, i.c.v.) failed to attenuate the hypothermic effect of 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg) and m-CPBG (40.0 nmol, i.c.v.) indicating that the brain 5-HT(7) receptor is not involved in the hypothermic effects of 8-OH-DPAT or m-CPBG. The obtained results suggest that the central 5-HT(7) receptor plays an essential role in the mediation of thermoregulation independent of 5-HT(1A) and 5-HT(3) receptors.

  19. PPPL tokamak program

    SciTech Connect

    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.

  20. A flowing liquid lithium limiter for the Experimental Advanced Superconducting Tokamak.

    PubMed

    Ren, J; Zuo, G Z; Hu, J S; Sun, Z; Yang, Q X; Li, J G; Zakharov, L E; Xie, H; Chen, Z X

    2015-02-01

    A program involving the extensive and systematic use of lithium (Li) as a "first," or plasma-facing, surface in Tokamak fusion research devices located at Institute of Plasma Physics, Chinese Academy of Sciences, was started in 2009. Many remarkable results have been obtained by the application of Li coatings in Experimental Advanced Superconducting Tokamak (EAST) and liquid Li limiters in the HT-7 Tokamak-both located at the institute. In furtherance of the lithium program, a flowing liquid lithium (FLiLi) limiter system has been designed and manufactured for EAST. The design of the FLiLi limiter is based on the concept of a thin flowing film which was previously tested in HT-7. Exploiting the capabilities of the existing material and plasma evaluation system on EAST, the limiter will be pre-wetted with Li and mechanically translated to the edge of EAST during plasma discharges. The limiter will employ a novel electro-magnetic pump which is designed to drive liquid Li flow from a collector at the bottom of limiter into a distributor at its top, and thus supply a continuously flowing liquid Li film to the wetted plasma-facing surface. This paper focuses on the major design elements of the FLiLi limiter. In addition, a simulation of incoming heat flux has shown that the distribution of heat flux on the limiter surface is acceptable for a future test of power extraction on EAST.

  1. Tokamak Systems Code

    SciTech Connect

    Reid, R.L.; Barrett, R.J.; Brown, T.G.; Gorker, G.E.; Hooper, R.J.; Kalsi, S.S.; Metzler, D.H.; Peng, Y.K.M.; Roth, K.E.; Spampinato, P.T.

    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.

  2. Microinjection of the 5-HT7 receptor antagonist SB-269970 into the rat brainstem and basal forebrain: site-dependent effects on REM sleep.

    PubMed

    Monti, Jaime M; Leopoldo, Marcello; Jantos, Héctor; Lagos, Patricia

    2012-08-01

    The effects of SB-269970, a selective 5-HT7 receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The 5-HT7 receptor ligand was microinjected into the horizontal limb of the diagonal band of Broca (HDB) and the laterodorsal tegmental nucleus (LDT) during the light period of the 12-h light/12-h dark cycle. For comparative purposes the compound was administered systemically and, in addition, injected directly into the dorsal raphe nucleus (DRN). Microinjection of SB-269970 into the HDB and the DRN induced a significant reduction of rapid-eye-movement sleep (REMS). Similar effects were observed after systemic administration of the 5-HT7 receptor antagonist. On the other hand, local infusion of the compound into the LDT provoked the opposite effect. It is proposed that the deactivation of GABAergic cells located in the HDB, DRN and LDT is responsible for the changes induced by SB-269970 on REM sleep values. It is suggested that the antidepressant effect of the 5-HT7 receptor antagonist could partly depend on the involvement of neuronal systems located in the DRN and the HDB.

  3. Effects of acupuncture at HT7 on glucose metabolism in a rat model of Alzheimer's disease: an 18F-FDG-PET study.

    PubMed

    Lai, Xinsheng; Ren, Jie; Lu, Yangjia; Cui, Shaoyang; Chen, Junqi; Huang, Yong; Tang, Chunzhi; Shan, Baoci; Nie, Bingbing

    2016-06-01

    To explore the effects of acupuncture at HT7 on different cerebral regions in a rat model of Alzheimer's disease (AD) with the application of (18)F-2-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET). Sixty Wistar rats were included after undergoing a Y-maze electric sensitivity test. Ten rats were used as a healthy control group. The remaining 50 rats were injected stereotaxically with ibotenic acid into the right nucleus basalis magnocellularis and injected intraperitoneally with D-galactose. AD was successfully modelled in 36 rats, which were randomly divided into three groups (n=12 each): the AD group, which remained untreated; the AD+HT7 group, which received 20 sessions of acupuncture at HT7 over 1 month; and the AD+Sham group, which received acupuncture at a distant non-acupuncture point. Total reaction time (TRT) was measured by Y-maze and (18)F-FDG-PET scans were conducted on day 1 and 30. PET images were processed with Statistical Parametric Mapping 8.0. Pre-treatment, TRT was greater in all AD groups versus controls (mean±SD 24.10±2.48 vs 41.34±5.00 s). Post-treatment, TRT was shortened in AD+HT7 versus AD+Sham and AD groups (p<0.0001, two-way analysis of variance). Glucose metabolic activity in the hippocampus, thalamus, hypothalamus, frontal lobe, and temporal lobe was decreased in AD rats compared with healthy controls and relatively elevated after HT7 acupuncture. Compared with sham acupuncture, HT7 needling had a greater positive influence on brain glucose metabolism. Needling at HT7 can improve memory ability and cerebral glucose metabolic activity of the hippocampus, thalamus, hypothalamus, and frontal/temporal lobes in an AD rat model. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. The role of the serotonin receptor subtypes 5-HT1A and 5-HT7 and its interaction in emotional learning and memory

    PubMed Central

    Stiedl, Oliver; Pappa, Elpiniki; Konradsson-Geuken, Åsa; Ögren, Sven Ove

    2015-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] is a multifunctional neurotransmitter innervating cortical and limbic areas involved in cognition and emotional regulation. Dysregulation of serotonergic transmission is associated with emotional and cognitive deficits in psychiatric patients and animal models. Drugs targeting the 5-HT system are widely used to treat mood disorders and anxiety-like behaviors. Among the fourteen 5-HT receptor (5-HTR) subtypes, the 5-HT1AR and 5-HT7R are associated with the development of anxiety, depression and cognitive function linked to mechanisms of emotional learning and memory. In rodents fear conditioning and passive avoidance (PA) are associative learning paradigms to study emotional memory. This review assesses the role of 5-HT1AR and 5-HT7R as well as their interplay at the molecular, neurochemical and behavioral level. Activation of postsynaptic 5-HT1ARs impairs emotional memory through attenuation of neuronal activity, whereas presynaptic 5-HT1AR activation reduces 5-HT release and exerts pro-cognitive effects on PA retention. Antagonism of the 5-HT1AR facilitates memory retention possibly via 5-HT7R activation and evidence is provided that 5HT7R can facilitate emotional memory upon reduced 5-HT1AR transmission. These findings highlight the differential role of these 5-HTRs in cognitive/emotional domains of behavior. Moreover, the results indicate that tonic and phasic 5-HT release can exert different and potentially opposing effects on emotional memory, depending on the states of 5-HT1ARs and 5-HT7Rs and their interaction. Consequently, individual differences due to genetic and/or epigenetic mechanisms play an essential role for the responsiveness to drug treatment, e.g., by SSRIs which increase intrasynaptic 5-HT levels thereby activating multiple pre- and postsynaptic 5-HTR subtypes. PMID:26300776

  5. The role of the serotonin receptor subtypes 5-HT1A and 5-HT7 and its interaction in emotional learning and memory.

    PubMed

    Stiedl, Oliver; Pappa, Elpiniki; Konradsson-Geuken, Åsa; Ögren, Sven Ove

    2015-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] is a multifunctional neurotransmitter innervating cortical and limbic areas involved in cognition and emotional regulation. Dysregulation of serotonergic transmission is associated with emotional and cognitive deficits in psychiatric patients and animal models. Drugs targeting the 5-HT system are widely used to treat mood disorders and anxiety-like behaviors. Among the fourteen 5-HT receptor (5-HTR) subtypes, the 5-HT1AR and 5-HT7R are associated with the development of anxiety, depression and cognitive function linked to mechanisms of emotional learning and memory. In rodents fear conditioning and passive avoidance (PA) are associative learning paradigms to study emotional memory. This review assesses the role of 5-HT1AR and 5-HT7R as well as their interplay at the molecular, neurochemical and behavioral level. Activation of postsynaptic 5-HT1ARs impairs emotional memory through attenuation of neuronal activity, whereas presynaptic 5-HT1AR activation reduces 5-HT release and exerts pro-cognitive effects on PA retention. Antagonism of the 5-HT1AR facilitates memory retention possibly via 5-HT7R activation and evidence is provided that 5HT7R can facilitate emotional memory upon reduced 5-HT1AR transmission. These findings highlight the differential role of these 5-HTRs in cognitive/emotional domains of behavior. Moreover, the results indicate that tonic and phasic 5-HT release can exert different and potentially opposing effects on emotional memory, depending on the states of 5-HT1ARs and 5-HT7Rs and their interaction. Consequently, individual differences due to genetic and/or epigenetic mechanisms play an essential role for the responsiveness to drug treatment, e.g., by SSRIs which increase intrasynaptic 5-HT levels thereby activating multiple pre- and postsynaptic 5-HTR subtypes.

  6. Stationary Flowing Liquid Lithium (SFLiLi) systems for tokamaks

    NASA Astrophysics Data System (ADS)

    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.

  7. Decreased agonist, but not antagonist, binding to the naturally occurring Thr92Lys variant of the h5-HT7(a) receptor.

    PubMed

    Brüss, Michael; Kiel, Sibylle; Bönisch, Heinz; Kostanian, Arevat; Göthert, Manfred

    2005-08-01

    In the present study on transfected human embryonic kidney (HEK)293 cells, we aimed at establishing whether expression of the naturally occurring Thr92Lys variation of the Gs-coupled h5-HT7(a) receptor leads to changes of ligand binding properties, of agonist-evoked cAMP formation and/or of antagonist-mediated blockade of the latter. Binding of [3H]5-carboxamidotryptamine ([3H]5-CT) to membranes and stimulated [3H]cAMP accumulation in whole cells were determined. Saturation binding experiments in membranes of transiently transfected cells expressing either the wild-type or the variant receptor revealed a single binding site in both cases and no difference in Bmax between both receptor isoforms. In competition binding experiments in membranes of stably transfected cells, the Thr92Lys variant exhibited a 2.8-11 times lower binding affinity of the ligands 5-hydroxytryptamine (5-HT), 5-CT, 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4yl)-1H-indole (RU24969), (+/-)-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) and sumatriptan compared to the wild-type receptor. However, the variant did not differ from the wild-type with respect to the binding properties of the antagonists (R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)-pyrrolodine-1-sulfonyl)phenol hydrochloride (SB-269970), risperidone, mesulergine and clozapine. In agreement with the decreased binding affinity of 5-HT, 5-CT, RU24969 and 8-OH-DPAT for the variant receptor, these agonists were less potent in stimulating [3H]cAMP accumulation in cells stably expressing the Thr92Lys h5-HT7(a) receptor. Sumatriptan did not stimulate cAMP accumulation in spite of its affinity for both receptor isoforms pointing to a putative weak antagonistic property of this drug at the h5-HT7 receptor. SB-269970 and clozapine were equipotent at both the variant and the wild-type receptor in producing a rightward shift of the 5-HT concentration-response curve for its stimulant effect on [3H]cAMP accumulation. In view of, e.g., the

  8. Identification of essential residues for binding and activation in the human 5-HT7(a) serotonin receptor by molecular modeling and site-directed mutagenesis

    PubMed Central

    Impellizzeri, Agata Antonina Rita; Pappalardo, Matteo; Basile, Livia; Manfra, Ornella; Andressen, Kjetil Wessel; Krobert, Kurt Allen; Messina, Angela; Levy, Finn Olav; Guccione, Salvatore

    2015-01-01

    The human 5-HT7 receptor is expressed in both the central nervous system and peripheral tissues and is a potential drug target in behavioral and psychiatric disorders. We examined molecular determinants of ligand binding and G protein activation by the human 5-HT7(a) receptor. The role of several key residues in the 7th transmembrane domain (TMD) and helix 8 were elucidated combining in silico and experimental mutagenesis. Several single and two double point mutations of the 5-HT7(a) wild type receptor were made (W7.33V, E7.35T, E7.35R, E7.35D, E7.35A, R7.36V, Y7.43A, Y7.43F, Y7.43T, R8.52D, D8.53K; E7.35T-R7.36V, R8.52D-D8.53K), and their effects upon ligand binding were assessed by radioligand binding using a potent agonist (5-CT) and a potent antagonist (SB269970). In addition, the ability of the mutated 5-HT7(a) receptors to activate G protein after 5-HT-stimulation was determined through activation of adenylyl cyclase. In silico investigation on mutated receptors substantiated the predicted importance of TM7 and showed critical roles of residues E7.35, W7.33, R7.36 and Y7.43 in agonist and antagonist binding and conformational changes of receptor structure affecting adenylyl cyclase activation. Experimental data showed that mutants E7.35T and E7.35R were incapable of ligand binding and adenylyl cyclase activation, consistent with a requirement for a negatively charged residue at this position. The mutant R8.52D was unable to activate adenylyl cyclase, despite unaffected ligand binding, consistent with the R8.52 residue playing an important role in the receptor-G protein interface. The mutants Y7.43A and Y7.43T displayed reduced agonist binding and AC agonist potency, not seen in Y7.43F, consistent with a requirement for an aromatic residue at this position. Knowledge of the molecular interactions important in h5-HT7 receptor ligand binding and G protein activation will aid the design of selective h5-HT7 receptor ligands for potential pharmacological use. PMID

  9. Identification of essential residues for binding and activation in the human 5-HT7(a) serotonin receptor by molecular modeling and site-directed mutagenesis.

    PubMed

    Impellizzeri, Agata Antonina Rita; Pappalardo, Matteo; Basile, Livia; Manfra, Ornella; Andressen, Kjetil Wessel; Krobert, Kurt Allen; Messina, Angela; Levy, Finn Olav; Guccione, Salvatore

    2015-01-01

    The human 5-HT7 receptor is expressed in both the central nervous system and peripheral tissues and is a potential drug target in behavioral and psychiatric disorders. We examined molecular determinants of ligand binding and G protein activation by the human 5-HT7(a) receptor. The role of several key residues in the 7th transmembrane domain (TMD) and helix 8 were elucidated combining in silico and experimental mutagenesis. Several single and two double point mutations of the 5-HT7(a) wild type receptor were made (W7.33V, E7.35T, E7.35R, E7.35D, E7.35A, R7.36V, Y7.43A, Y7.43F, Y7.43T, R8.52D, D8.53K; E7.35T-R7.36V, R8.52D-D8.53K), and their effects upon ligand binding were assessed by radioligand binding using a potent agonist (5-CT) and a potent antagonist (SB269970). In addition, the ability of the mutated 5-HT7(a) receptors to activate G protein after 5-HT-stimulation was determined through activation of adenylyl cyclase. In silico investigation on mutated receptors substantiated the predicted importance of TM7 and showed critical roles of residues E7.35, W7.33, R7.36 and Y7.43 in agonist and antagonist binding and conformational changes of receptor structure affecting adenylyl cyclase activation. Experimental data showed that mutants E7.35T and E7.35R were incapable of ligand binding and adenylyl cyclase activation, consistent with a requirement for a negatively charged residue at this position. The mutant R8.52D was unable to activate adenylyl cyclase, despite unaffected ligand binding, consistent with the R8.52 residue playing an important role in the receptor-G protein interface. The mutants Y7.43A and Y7.43T displayed reduced agonist binding and AC agonist potency, not seen in Y7.43F, consistent with a requirement for an aromatic residue at this position. Knowledge of the molecular interactions important in h5-HT7 receptor ligand binding and G protein activation will aid the design of selective h5-HT7 receptor ligands for potential pharmacological use.

  10. The 5-HT(7) receptor antagonist SB 269970 counteracts restraint stress-induced attenuation of long-term potentiation in rat frontal cortex.

    PubMed

    Tokarski, K; Bobula, B; Kusek, M; Hess, G

    2011-12-01

    The effects of restraint lasting for 10 min, repeated twice daily for 3 days, were studied ex vivo in rat frontal cortex slices prepared 24 h after the last stress session. In slices originating from stressed animals, the amplitude of extracellular field potentials recorded in cortical layer II/III was increased. Stress also resulted in a reduced magnitude of long-term potentiation (LTP) of field potentials. In a separate experimental group, rats were subjected to restraint lasting for 10 min, twice daily for 3 days but, additionally, animals received injections of 5-HT(7) receptor antagonist SB 269970 (1.25 mg/kg) before each restraint stress session. In this group, the amplitude of field potentials and the magnitude of LTP were not different from the control, indicating that stress-induced modifications of basal glutamatergic transmission and synaptic plasticity were prevented by the 5-HT(7) receptor antagonist.

  11. Synthesis and structure-activity relationships of new carbonyl guanidine derivatives as novel dual 5-HT2B and 5-HT7 receptor antagonists.

    PubMed

    Moritomo, Ayako; Yamada, Hiroyoshi; Watanabe, Toshihiro; Itahana, Hirotsune; Akuzawa, Shinobu; Okada, Minoru; Ohta, Mitsuaki

    2013-12-15

    To identify potent dual 5-HT2B and 5-HT7 receptor antagonists, we synthesized a series of novel carbonyl guanidine derivatives and examined their structure-activity relationships. Among these compounds, N-(9-hydroxy-9H-fluorene-2-carbonyl)guanidine (10) had a good in vitro profile, that is, potent affinity for human 5-HT2B and 5-HT7 receptor subtypes (Ki=1.8 nM and Ki=17.6 nM, respectively) and high selectivity over 5-HT2A, 5-HT2C, α1, D2 and M1 receptors. Compound 10 also showed a suppressing effect on 5-HT-induced dural protein extravasation in guinea pigs when orally administered.

  12. Effects of the selective 5-HT7 receptor antagonist SB-269970 on premature responding in the five-choice serial reaction time test in rats.

    PubMed

    Nikiforuk, Agnieszka; Hołuj, Małgorzata; Potasiewicz, Agnieszka; Popik, Piotr

    2015-08-01

    The antagonists of serotonin 5-HT7 receptors have been demonstrated to ameliorate cognitive impairments in pharmacological animal models of schizophrenia that involve blockade of N-methyl-D-aspartate receptors (NMDARs). The administration of NMDAR antagonists evokes a broad range of cognitive deficits, including a loss of impulse control. The involvement of 5-HT7 receptors in the modulation of impulsivity has been recently suggested but has not been studied in great detail. The aim of the present study was to examine the effect of a selective 5-HT7 receptor antagonist SB-269970 on a measure of impulsive action, i.e., premature responding on the five-choice serial reaction time task (5-CSRTT) in rats. The antagonist of 5-HT2A receptor M100,907 was used as a positive control. The efficacies of both compounds were assessed in conditions of increased impulsivity that were produced by the administration of the NMDAR antagonist MK-801 or/and non-drug stimuli, i.e., using variable inter-trial intervals (vITIs). To examine the general ability of SB-269970 to counteract the MK-801-induced impairments, a discrete paired-trial delayed alternation task in a T-maze was employed. MK-801 significantly increased the number of premature responses in 5-CSRTT, and this effect was abolished by the administration of M100,907 (0.5 mg/kg) and SB-269970 (1 mg/kg). In addition, M100,907, but not SB-269970, reduced premature responding in the prolonged ITI trials. Both M100,907 and SB-269970 attenuated MK-801-induced working memory impairment in a T-maze. The present study demonstrated the efficacy of SB-269970 against MK-801-induced premature responding in the 5-CSRTT. This anti-impulsive action may offer additional benefits to the cognitive-enhancing effects of pharmacological blockade of 5-HT7 receptors.

  13. The Serotonin 5-HT7Dro Receptor Is Expressed in the Brain of Drosophila, and Is Essential for Normal Courtship and Mating

    PubMed Central

    Becnel, Jaime; Johnson, Oralee; Luo, Jiangnan; Nässel, Dick R.; Nichols, Charles D.

    2011-01-01

    The 5-HT7 receptor remains one of the less well characterized serotonin receptors. Although it has been demonstrated to be involved in the regulation of mood, sleep, and circadian rhythms, as well as relaxation of vascular smooth muscles in mammals, the precise mechanisms underlying these functions remain largely unknown. The fruit fly, Drosophila melanogaster, is an attractive model organism to study neuropharmacological, molecular, and behavioral processes that are largely conserved with mammals. Drosophila express a homolog of the mammalian 5-HT7 receptor, as well as homologs for the mammalian 5-HT1A, and 5-HT2, receptors. Each fly receptor couples to the same effector pathway as their mammalian counterpart and have been demonstrated to mediate similar behavioral responses. Here, we report on the expression and function of the 5-HT7Dro receptor in Drosophila. In the larval central nervous system, expression is detected postsynaptically in discreet cells and neuronal circuits. In the adult brain there is strong expression in all large-field R neurons that innervate the ellipsoid body, as well as in a small group of cells that cluster with the PDF-positive LNvs neurons that mediate circadian activity. Following both pharmacological and genetic approaches, we have found that 5-HT7Dro activity is essential for normal courtship and mating behaviors in the fly, where it appears to mediate levels of interest in both males and females. This is the first reported evidence of direct involvement of a particular serotonin receptor subtype in courtship and mating in the fly. PMID:21674056

  14. Spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors, are involved in antinociception by systemically administered amitriptyline.

    PubMed

    Liu, Jean; Reid, Allison R; Sawynok, Jana

    2013-01-05

    The present study explored a link between spinal 5-HT(7) and adenosine A(1) receptors in antinociception by systemic amitriptyline in normal and adenosine A(1) receptor knock-out mice using the 2% formalin test. In normal mice, antinociception by systemic amitriptyline 3mg/kg was blocked by intrathecal administration of the selective adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) 10 nmol. Blockade was also seen in adenosine A(1) receptor +/+ mice, but not in -/- mice lacking these receptors. In both normal and adenosine A(1) receptor +/+ mice, the selective 5-HT(7) receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB269970) 3 μg blocked antinociception by systemic amitriptyline, but it did not prevent antinociception in adenosine A(1) receptor -/- mice. In normal mice, flinching was unaltered when the selective 5-HT(7) receptor agonist (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin (AS-19) 20 μg was administered alone, but increased when co-administered intrathecally with DPCPX 10 nmol or SB269970 3 μg. Intrathecal AS-19 decreased flinching in adenosine A(1) receptor +/+ mice compared to -/- mice. Systemic amitriptyline appears to reduce nociception by activating spinal adenosine A(1) receptors secondarily to 5-HT(7) receptors. Spinal actions constitute only one aspect of antinociception by amitriptyline, as intraplantar DPCPX 10 nmol blocked antinociception by systemic amitriptyline in normal and adenosine A(1) receptor +/+, but not -/- mice. Adenosine A(1) receptor interactions are worthy of attention, as chronic oral caffeine (0.1, 0.3g/L, doses considered relevant to human intake levels) blocked antinociception by systemic amitriptyline in normal mice. In conclusion, adenosine A(1) receptors contribute to antinociception by systemic amitriptyline in both spinal and peripheral compartments.

  15. The serotonin 5-HT7 receptor agonist LP-44 microinjected into the dorsal raphe nucleus suppresses REM sleep in the rat.

    PubMed

    Monti, Jaime M; Leopoldo, Marcello; Jantos, Héctor

    2008-08-22

    The effects of LP-44, a selective 5-HT7 receptor agonist, and of SB-269970, a selective 5-HT7 receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The 5-HT7 receptor ligands were microinjected directly into the dorsal raphe nucleus (DRN) during the light period of the 12-h light/12-h dark cycle. Infusion of LP-44 (1.25-5.0 mM) into the DRN induced a significant reduction of rapid-eye-movement sleep (REMS) and of the number of REM periods. Similar effects were observed after the direct administration into the DRN of SB-269970 (0.5-1.0 mM). Pretreatment with a dose of SB-269970 (0.5 mM) that significantly affects sleep variables antagonized the LP-44 (2.5 mM)-induced suppression of REMS and of the number of REM periods. It is proposed that the suppression of REMS after microinjection of LP-44 into the DRN is related, at least in part, to the activation of GABAergic neurons in the DRN that contribute to long projections that reach, among others, the laterodorsal and pedunculopontine tegmental nuclei involved in the promotion of REMS.

  16. Acupuncture stimulation at HT7 alleviates depression-induced behavioral changes via regulation of the serotonin system in the prefrontal cortex of maternally-separated rat pups.

    PubMed

    Park, Hyemee; Yoo, Doyoung; Kwon, Sunoh; Yoo, Tae-Won; Park, Hi-Joon; Hahm, Dae-Hyun; Lee, Hyejung; Kim, Seung-Tae

    2012-07-01

    A possible application of acupuncture in alleviating depression-like behavioral changes and regulating serotonin signaling in the prefrontal cortex (PFC) of maternally-separated rat pups was investigated in this study. On postnatal day 15, rat pups were maternally-separated and received acupuncture stimulation at acupoint HT7 or ST36 once a day for 7 days. On postnatal day 21, the tail suspension test was performed and the PFC was harvested. Tissue levels of serotonin (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) were then measured by high-performance liquid chromatography and expression of serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) were assessed by western blotting. Levels of 5-HT and 5-HIAA were not significantly changed, but the 5-HIAA/5-HT ratio was significantly increased by maternal separation. The immobility time of maternally-separated rat pups was increased, and increased 5-HTT expression and reduced BDNF level were observed in the PFC. But acupuncture stimulation at HT7 alleviated the behavioral change and regulated the changes of 5-HIAA/5-HT ratio, 5-HTT, and BDNF. In conclusion, acupuncture stimulation at HT7 can relieve maternal separation-induced changes, and we propose that regulation of the 5-HIAA/5-HT ratio and of 5-HTT expression by acupuncture stimulation are important acupuncture-induced benefits in this animal model of depression.

  17. Intrathecal nefopam-induced antinociception through activation of descending serotonergic projections involving spinal 5-HT7 but not 5-HT3 receptors.

    PubMed

    Lee, Hyung Gon; Kim, Woong Mo; Kim, Joung Min; Bae, Hong-Beom; Choi, Jeong Il

    2015-02-05

    We examined the involvement of spinal 5-HT(5-hydroxytryptamine) receptor 3(5-HT3R) and 7(5-HT7R) as well as the overall role of descending serotonergic projections in the analgesic effects of intrathecal(i.t.) nefopam for two rat models of formalin and paw incision test. I.t. nefopam produced an antinociceptive effect in a dose-dependent manner in both tests. Lesioning the spinal serotonergic projections using i.t. 5,7-dihydroxytryptamine(5,7-DHT) did not influence the intensity of allodynia in the paw incision test, but i.t. 5,7-DHT abolished the effect of nefopam. In the formain test, i.t. 5,7-DHT alone significantly diminished the flinches, but the effect of nefopam was not affected by i.t. 5,7-DHT. Antagonism study showed that i.t. 5-HT7R antagonist, SB269970 significantly blocked the antinociceptive effect of nefopam in both tests, but i.t. 5-HT3R antagonist, ondansetron has no influence on the effect of nefopam. The present study demonstrates that descending spinal serotonergic projections play a vital role in antinociceptive effect of i.t. nefopam in the paw incision test, but indeterminate in the formalin test. In both tests, the antinociceptive effect of i.t. nefopam involves the spinal 5-HT7R, but not 5-HT3R.

  18. Aminoalkyl Derivatives of 8-Alkoxypurine-2,6-diones: Multifunctional 5-HT1A /5-HT7 Receptor Ligands and PDE Inhibitors with Antidepressant Activity.

    PubMed

    Chłoń-Rzepa, Grażyna; Zagórska, Agnieszka; Żmudzki, Paweł; Bucki, Adam; Kołaczkowski, Marcin; Partyka, Anna; Wesołowska, Anna; Kazek, Grzegorz; Głuch-Lutwin, Monika; Siwek, Agata; Starowicz, Gabriela; Pawłowski, Maciej

    2016-12-01

    In the search for potential psychotropic agents, a new series of 3,7-dimethyl- and 1,3-dimethyl-8-alkoxypurine-2,6-dione derivatives of arylpiperazines, perhydroisoquinolines, or tetrahydroisoquinolines with flexible alkylene spacers (5-16 and 21-32) were synthesized and evaluated for 5-HT1A /5-HT7 receptor affinities as well as PDE4B1 and PDE10A inhibitory properties. The 1-(4-(4-(2-hydroxyphenyl)piperazin-1-yl)butyl)-3,7-dimethyl-8-propoxypurine-2,6-dione (16) and 7-(2-hydroxyphenyl)piperazinylalkyl-1,3-dimethyl-8-ethoxypurine-2,6-diones (31 and 32) as potent dual 5-HT1A /5-HT7 receptor ligands with antagonistic activity produced an antidepressant-like effect in the forced swim test in mice. This effect was similar to that produced by citalopram. All the tested compounds were stronger phosphodiesterase isoenzyme inhibitors than theophylline and theobromine. The most potent compounds, 15 and 16, were characterized by 51 and 52% inhibition, respectively, of PDE4B1 activity at a concentration of 10(-5)  M. Concerning the above findings, it may be assumed that the inhibition of PDE4B1 may impact on the signal strength and specificity resulting from antagonism toward the 5-HT1 and 5-HT7 receptors, especially in the case of compounds 15 and 16. This dual receptor and enzyme binding mode was analyzed and explained via molecular modeling studies.

  19. In Vivo Effect of a 5-HT7 Receptor Agonist on 5-HT Neurons and GABA Interneurons in the Dorsal Raphe Nuclei of Sham and PD Rats.

    PubMed

    Wang, Shuang; Zhao, Yan; Gao, Jie; Guo, Yufang; Wang, Xiang; Huo, Jian; Wei, Ping; Cao, Jian

    2017-03-01

    The 5-hydroxytryptamine (5-HT; serotonin) neurotransmission is severely affected by the degeneration of nigrostriatal dopaminergic neurons. Here, we report the effects of the systemic administration of the 5-HT7 receptor agonist AS-19. In sham rats, the mean response of the 5-HT neurons in the dorsal raphe nucleus (DRN) to systemic AS-19 was excitatory and the mean response of the γ-aminobutyric acid (GABA) interneurons was inhibitory. In Parkinson disease (PD) rats, the same dose did not affect the 5-HT neurons and only high doses (640 μg/kg intravenous) were able to the increase GABA interneuron activity. These results indicate that DRN 5-HT neurons and GABA interneurons are regulated by the activation of 5-HT7 receptors and that the degeneration of the nigrostriatal pathway leads to decreased responses of these neurons to AS-19, which in turn suggests that the 5-HT7 receptors on 5-HT neurons and GABA interneurons in PD rats are dysfunctional and downregulated.

  20. A flowing liquid lithium limiter for the Experimental Advanced Superconducting Tokamak

    NASA Astrophysics Data System (ADS)

    Ren, J.; Zuo, G. Z.; Hu, J. S.; Sun, Z.; Yang, Q. X.; Li, J. G.; Zakharov, L. E.; Xie, H.; Chen, Z. X.

    2015-02-01

    A program involving the extensive and systematic use of lithium (Li) as a "first," or plasma-facing, surface in Tokamak fusion research devices located at Institute of Plasma Physics, Chinese Academy of Sciences, was started in 2009. Many remarkable results have been obtained by the application of Li coatings in Experimental Advanced Superconducting Tokamak (EAST) and liquid Li limiters in the HT-7 Tokamak—both located at the institute. In furtherance of the lithium program, a flowing liquid lithium (FLiLi) limiter system has been designed and manufactured for EAST. The design of the FLiLi limiter is based on the concept of a thin flowing film which was previously tested in HT-7. Exploiting the capabilities of the existing material and plasma evaluation system on EAST, the limiter will be pre-wetted with Li and mechanically translated to the edge of EAST during plasma discharges. The limiter will employ a novel electro-magnetic pump which is designed to drive liquid Li flow from a collector at the bottom of limiter into a distributor at its top, and thus supply a continuously flowing liquid Li film to the wetted plasma-facing surface. This paper focuses on the major design elements of the FLiLi limiter. In addition, a simulation of incoming heat flux has shown that the distribution of heat flux on the limiter surface is acceptable for a future test of power extraction on EAST.

  1. A flowing liquid lithium limiter for the Experimental Advanced Superconducting Tokamak

    SciTech Connect

    Ren, J.; Zuo, G. Z.; Hu, J. S.; Sun, Z.; Yang, Q. X.; Li, J. G.; Xie, H.; Chen, Z. X.; Zakharov, L. E.

    2015-02-15

    A program involving the extensive and systematic use of lithium (Li) as a “first,” or plasma-facing, surface in Tokamak fusion research devices located at Institute of Plasma Physics, Chinese Academy of Sciences, was started in 2009. Many remarkable results have been obtained by the application of Li coatings in Experimental Advanced Superconducting Tokamak (EAST) and liquid Li limiters in the HT-7 Tokamak—both located at the institute. In furtherance of the lithium program, a flowing liquid lithium (FLiLi) limiter system has been designed and manufactured for EAST. The design of the FLiLi limiter is based on the concept of a thin flowing film which was previously tested in HT-7. Exploiting the capabilities of the existing material and plasma evaluation system on EAST, the limiter will be pre-wetted with Li and mechanically translated to the edge of EAST during plasma discharges. The limiter will employ a novel electro-magnetic pump which is designed to drive liquid Li flow from a collector at the bottom of limiter into a distributor at its top, and thus supply a continuously flowing liquid Li film to the wetted plasma-facing surface. This paper focuses on the major design elements of the FLiLi limiter. In addition, a simulation of incoming heat flux has shown that the distribution of heat flux on the limiter surface is acceptable for a future test of power extraction on EAST.

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

    SciTech Connect

    Weiland, Jan

    2014-12-15

    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{sub 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.

  3. Options for commercial tokamaks

    SciTech Connect

    Dabiri, A.E.; Keeton, D.C.; Thomson, S.L.

    1986-07-01

    Systems studies have been performed at the Fusion Engineering Design Center (FEDC) to assess commercial tokamak options. One study investigates the economics of high-beta operation and determines an optimum operating range of 10 to 20% beta, with a corresponding neutron wall loading of 6 to 8 MW/m/sup 2/. A second study determines conditions under which small, low-power tokamaks can be economically combined into a 1200-MW(electric) multiplex power plant. The results of these studies have directed future efforts at the FEDC toward a high-beta, tokamak design using a modular maintenance configuration.

  4. Tokamak reactor studies

    SciTech Connect

    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.

  5. Tokamak ARC damage

    SciTech Connect

    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.

  6. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome

    PubMed Central

    Costa, Lara; Sardone, Lara M.; Lacivita, Enza; Leopoldo, Marcello; Ciranna, Lucia

    2015-01-01

    Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome

  7. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome.

    PubMed

    Costa, Lara; Sardone, Lara M; Lacivita, Enza; Leopoldo, Marcello; Ciranna, Lucia

    2015-01-01

    Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome.

  8. Modular tokamak magnetic system

    DOEpatents

    Yang, Tien-Fang

    1988-01-01

    A modular tokamak system comprised of a plurality of interlocking moldules. Each module is comprised of a vacuum vessel section, a toroidal field coil, moldular saddle coils which generate a poloidal magnetic field and ohmic heating coils.

  9. Selective blockade of 5-hydroxytryptamine (5-HT)7 receptors enhances 5-HT transmission, antidepressant-like behavior, and rapid eye movement sleep suppression induced by citalopram in rodents.

    PubMed

    Bonaventure, Pascal; Kelly, Lisa; Aluisio, Leah; Shelton, Jonathan; Lord, Brian; Galici, Ruggero; Miller, Kirsten; Atack, John; Lovenberg, Timothy W; Dugovic, Christine

    2007-05-01

    Evidence has accumulated supporting a role for 5-hydroxytryptamine (5-HT)7 receptors in circadian rhythms, sleep, and mood disorders, presumably as a consequence of the modulation of 5-HT-mediated neuronal activity. We hypothesized that a selective 5-HT7 receptor antagonist, (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]-pyrrolidine (SB-269970), should increase activity of 5-HT neurons and potentiate the effect of selective serotonin reuptake inhibitors (citalopram). In rats, administration of 3 mg/kg s.c. citalopram alone increased the extracellular concentration of 5-HT. This effect of citalopram on extracellular 5-HT concentration was significantly enhanced by an ineffective dose of SB-269970. Combining this dose of SB-269970 with a low dose of citalopram also resulted in a significant increase in extracellular concentration of 5-HT, suggesting a potentiation of neurochemical effects. In mice, citalopram and SB-269970 dose-dependently decreased immobility time in the tail suspension test. The dose-effect curve of citalopram was shifted leftward by coadministration of an effective dose of SB-269970. Furthermore, combining ineffective doses of citalopram and SB-269970 also resulted in a significant decrease of immobility time in the tail suspension test, suggesting potentiation of antidepressant-like effects. In rats, SB-269970 potentiated the increase of rapid eye movement (REM) latency and the REM sleep decrease induced by citalopram. SB-269970 also reversed the increase in sleep fragmentation induced by citalopram. Rat plasma and brain concentrations of citalopram were not affected by coadministration of SB-269970, arguing for a pharmacodynamic rather than a pharmacokinetic mechanism. Overall, these results indicate that selective blockade of 5-HT7 receptors may enhance the antidepressant efficacy of citalopram and may provide a novel therapy to alleviate sleep disturbances associated with depression.

  10. Role of 5-HT(1A) and 5-HT(7) receptors in the facilitatory response induced by 8-OH-DPAT on learning consolidation.

    PubMed

    Meneses, A; Terrón, J A

    2001-06-01

    The present study further explored the mechanisms involved in the facilitatory effect induced by (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on learning consolidation. For this purpose, we analyzed in parallel the effects of LY215840 and ritanserin, two 5-HT(2) receptor antagonists with high affinity for the 5-HT(7) receptor, and WAY100635, a selective 5-HT(1A) receptor antagonist, on the facilitatory effect induced by 8-OH-DPAT on learning consolidation. We also determined whether LY215840 and/or ritanserin could be beneficial in restoring a deficient learning condition. Using the model of autoshaping task, post-training injection of LY215840 or WAY100635 had no effect on learning consolidation. However, both drugs abolished the enhancing effect of 8-OH-DPAT, with LY215840 being slightly more effective than WAY100635 in this respect. Ritanserin produced an increase in performance by itself and also abolished the effect of 8-OH-DPAT. Remarkably, selective blockade of 5-HT(2A) and 5-HT(2B/2C) receptors with MDL100907 and SB200646, respectively, failed to alter the 8-OH-DPAT effect. LY215840 and ritanserin, at the doses that inhibited the 8-OH-DPAT-induced response, reversed the learning deficits induced by scopolamine and dizocilpine. The present results suggest that the enhancing effect produced by 8-OH-DPAT on learning consolidation involves activation of 5-HT(1A) receptors and an additional mechanism, probably related to the 5-HT(7) receptor. Blockade of 5-HT(2) receptors, and perhaps of 5-HT(7) receptors as well, may provide some benefit in reversing learning deficits associated with decreased cholinergic and/or glutamatergic neurotransmission.

  11. Improvising 5-HT7R homology model for design of high affinity ligands: model validation with docking, embrace minimization, MM-GBSA, and molecular dynamic simulations.

    PubMed

    Jha, Preeti; Chaturvedi, Shubhra; Swastika; Pal, Sunil; Jain, Nidhi; Mishra, Anil K

    2017-08-09

    The subtype, 5-HT7R has been implicated in neurological disorders and presents itself as a promising target for antidepressant drugs. Design of targeted selective ligands, require a sound knowledge of 3D-receptor structure. In absence of receptor structure, structure-based design of targeted ligands relies on generation of 5-HT7R homology model. In this study, the impact of template choice, alignment, and model building methods on the homology model of 5-HT7R is addressed. The compactness and model quality due to the presence of cholesterol (lipidic receptor) have also been observed. The results suggest good stereochemical quality of the final model. Ramachandran Plot Analysis indicated more than 97.5% amino acid residues in the favorable region. The overall quality factor was 91.8% using ERRAT. The Z-score for backbone confirmation and packing quality were -1.248 and -1.427, respectively, using WHATCHECK. The RMS Z-score for side chain planarity was .711. Other validation results for the final model include binding site analysis in which Asp162, Val163, Phe343, Phe344, Arg350, Arg367, and Leu370 conserved residues were found in the active site, correlation coefficient of .82 in ligand-based screening and .85 in embrace minimization. Further, the model showed good correlation for agonist and antagonist in docking ([Formula: see text] ≈ .76, [Formula: see text] ≈ .82), embrace minimization ([Formula: see text] ≈ .73, [Formula: see text] ≈ .72), and MM-GBSA ([Formula: see text] ≈ .69, [Formula: see text] ≈ .75) studies. The model was subjected to Molecular Dynamics (MD) simulation of 20 ns both in ligand-free and ligand-bound receptor (agonist and antagonist) system in order to assess its stability.

  12. Brown adipose tissue sympathetic nerve activity is potentiated by activation of 5-hydroxytryptamine (5-HT)1A/5-HT7 receptors in the rat spinal cord

    PubMed Central

    Madden, C. J.; Morrison, S. F.

    2008-01-01

    In urethane-chloralose anesthetized, neuromuscularly blocked, ventilated rats, microinjection of NMDA (12 pmol) into the right fourth thoracic segment (T4) spinal intermediolateral nucleus (IML) immediately increased ipsilateral brown adipose tissue (BAT) sympathetic nerve activity (SNA; peak +492% of control), expired CO2 (+0.1%) heart rate (+48 beats min−1) and arterial pressure (+8 mmHg). The increase in BAT SNA evoked by T4 IML microinjection of NMDA was potentiated when it was administered immediately following a T4 IML microinjection of 5-hydroxytryptamine (5-HT, 100 pmol) or the 5-HT1A/5-HT7 receptor agonist, 8-OH-DPAT (600 pmol), (area under the curve: 184%, and 259% of the NMDA-only response, respectively). In contrast, T4 IML microinjection of the 5-HT2 receptor agonist, DOI (28 pmol) did not potentiate the NMDA-evoked increase in BAT SNA (101% of NMDA-only response). Microinjection into the T4 IML of the selective 5-HT1A antagonist, WAY-100635 (500 pmol), plus the 5-HT7 antagonist, SB-269970 (500 pmol), prevented the 5-HT-induced potentiation of the NMDA-evoked increase in BAT SNA. When administered separately, WAY-100635 (800 pmol) and SB-269970 (800 pmol) attenuated the 8-OH-DPAT-induced potentiation of the NMDA-evoked increase in BAT SNA through effects on the amplitude and duration of the response, respectively. The selective 5-HT2 receptor antagonist, ketanserin (100 pmol), did not attenuate the potentiations of the NMDA-evoked increase in BAT SNA induced by either 5-HT or 8-OH-DPAT. These results demonstrate that activation of 5-HT1A/5-HT7 receptors can act synergistically with NMDA receptor activation within the IML to markedly increase BAT SNA. PMID:18082230

  13. Emotional and risk seeking behavior after prepuberal subchronic or adult acute stimulation of 5-HT7-Rs in Naples High Excitability rats.

    PubMed

    Ruocco, Lucia A; Romano, Emilia; Treno, Concetta; Lacivita, Enza; Arra, Claudio; Gironi-Carnevale, Ugo A; Travaglini, Domenica; Leopoldo, Marcello; Laviola, Giovanni; Sadile, Adolfo G; Adriani, Walter

    2014-04-01

    We report here the results of studies aimed to investigate the involvement of serotonin receptor 7 subtype (5-HT7-R) in the modulation of emotional response in Naples High-Excitability (NHE) rat, a validated model for hyperactivity and impaired attention. A range of dosages (0.0, 0.125, 0.250, or 0.500 mg/kg) of LP-211, a selective agonist of 5-HT7-Rs, has been evaluated in animals at different age (adolescence and adulthood). Male NHE and random bred (NRB) control rats were tested in an Elevated Zero-Maze (EZM) after LP-211 treatment in two different regimens: at the issue of adolescent, subchronic exposure (14 intraperitoneal [i.p.] injections, once/day, pnd 31-44, tested on pnd 45--Exp. 1) or as adult, acute effect (15 min after i.p. injection--Exp. 2). Adolescent, subchronic LP-211 at 0.500 mg/kg dosage increased the frequency of head-dips only in NHE rats. Drug effect on time spent and entries in open EZM quadrants were revealed with adult, acute administration of 0.125 mg/kg LP-211 (both strains), indicating a tendency toward anxiolytic effects. In conclusion, data demonstrate that subchronic stimulation of 5-HT7-Rs during prepuberal period increases novelty-seeking/risk-taking propensity in NHE adults. These sequels are revealing increased disinhibition and/or motivation to explore in the NHE rats, which are characterized by a hyperactive dopaminergic system. These data may open new perspectives in studying mechanism of risk-seeking behavior.

  14. An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT7 and 5-HT1A Receptor Partial Agonist that Corrects Motor Stereotypy in Mouse Models.

    PubMed

    Canal, Clinton E; Felsing, Daniel E; Liu, Yue; Zhu, Wanying; Wood, JodiAnne T; Perry, Charles K; Vemula, Rajender; Booth, Raymond G

    2015-07-15

    Stereotypy (e.g., repetitive hand waving) is a key phenotype of autism spectrum disorder, Fragile X and Rett syndromes, and other neuropsychiatric disorders, and its severity correlates with cognitive and attention deficits. There are no effective treatments, however, for stereotypy. Perturbation of serotonin (5-HT) neurotransmission contributes to stereotypy, suggesting that distinct 5-HT receptors may be pharmacotherapeutic targets to treat stereotypy and related neuropsychiatric symptoms. For example, preclinical studies indicate that 5-HT7 receptor activation corrects deficits in mouse models of Fragile X and Rett syndromes, and clinical trials for autism are underway with buspirone, a 5-HT1A partial agonist with relevant affinity at 5-HT7 receptors. Herein, we report the synthesis, in vitro molecular pharmacology, behavioral pharmacology, and pharmacokinetic parameters in mice after subcutaneous and oral administration of (+)-5-(2'-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine ((+)-5-FPT), a new, dual partial agonist targeting both 5-HT7 (Ki = 5.8 nM, EC50 = 34 nM) and 5-HT1A (Ki = 22 nM, EC50 = 40 nM) receptors. Three unique, heterogeneous mouse models were used to assess the efficacy of (+)-5-FPT to reduce stereotypy: idiopathic jumping in C58/J mice, repetitive body rotations in C57BL/6J mice treated with the NMDA antagonist, MK-801, and repetitive head twitching in C57BL/6J mice treated with the 5-HT2 agonist, DOI. Systemic (+)-5-FPT potently and efficaciously reduced or eliminated stereotypy in each of the mouse models without altering locomotor behavior on its own, and additional tests showed that (+)-5-FPT, at the highest behaviorally active dose tested, enhanced social interaction and did not cause behaviors indicative of serotonin syndrome. These data suggest that (+)-5-FPT is a promising medication for treating stereotypy in psychiatric disorders.

  15. [3H]-Mesulergine labels 5-HT7 sites in rat brain and guinea-pig ileum but not rat jejunum

    PubMed Central

    Hemedah, Maggie; Coupar, Ian M; Mitchelson, Fred J

    1999-01-01

    The primary aim of this investigation was to determine whether binding sites corresponding to the 5-HT7 receptor could be detected in smooth muscle of the rat jejunum. Binding studies in rat brain (whole brain minus cerebellum) and guinea-pig ileal longitudinal muscle were also undertaken in order to compare the binding characteristics of these tissues. Studies were performed using [3H]-mesulergine, as it has a high affinity for 5-HT7 receptors.In the rat brain and guinea-pig ileum, pKD values for [3H]-mesulergine of 8.0±0.04 and 7.9±0.11 (n=3) and Bmax values of 9.9±0.3 and 21.5±4.9 fmol mg−1 protein were obtained respectively, but no binding was detected in the rat jejunum. [3H]-mesulergine binding in the rat brain and guinea-pig ileum was displaced with the agonists 5-carboxamidotryptamine (5-CT)>5-hydroxytryptamine (5-HT)⩾5-methoxytryptamine (5-MeOT)>sumatriptan and the antagonists risperidone⩾LSD⩾metergoline>ritanserin>>pindolol.Despite the lack of [3H]-mesulergine binding in the rat jejunum, functional studies undertaken revealed a biphasic contractile response to 5-HT which was partly blocked by ondansetron (1 μM). The residual response was present in over 50% of tissues studied and was found to be inhibited by risperidone>LSD>metergoline>mesulergine=ritanserin>pindolol, but was unaffected by RS 102221 (3 μM), cinanserin (30 nM), yohimbine (0.1 μM) and GR 113808 (1 μM). In addition, the agonist order of potency was 5-CT>5-HT>5-MeOT>sumatriptan.In conclusion, binding studies performed with [3H]-mesulergine were able to detect 5-HT7 sites in rat brain and guinea-pig ileum, but not in rat jejunum, where a functional 5-HT7-like receptor was present. PMID:10051134

  16. The relaxant 5-HT receptor in the dog coronary artery smooth muscle: pharmacological resemblance to the cloned 5-ht7 receptor subtype.

    PubMed Central

    Terrón, J. A.

    1996-01-01

    1. The relaxant effect of 5-hydroxytryptamine (5-HT) in the dog isolated coronary artery deprived of endothelium is mediated by a receptor unrelated to the 5-HT1, 5-HT2, 5-HT3 or 5-HT4 types. Based upon the pharmacological characteristics of this relaxant 5-HT receptor and those reported for the new members of the 5-HT receptor family, the present study explored the possibility that the relaxant 5-HT receptor referred to above, corresponds to the cloned 5-ht7 subtype. Thus, the relaxing and/or blocking effects of several 5-HT receptor drugs as well as some typical and atypical antipsychotic drugs with high affinity for the cloned 5-ht7 receptor in precontracted ring segments were analyzed. 2. 5-HT, 5-carboxamidotryptamine (5-CT) and 5-methoxytryptamine, but not 8-OH-DPAT or sumatriptan, produced concentration-dependent relaxations in endothelium-denuded canine coronary artery rings precontracted with prostaglandin F2a (2 microM). Clozapine (1 microM) produced in some cases a small relaxing effect and antagonized 5-HT- and 5-CT-induced relaxation suggesting a partial agonist effect. In the presence of the 5-HT1D receptor antagonist, GR127935 (100 nM), the rank order of agonist potency was 5-CT > 5-HT > clozapine > or = 5-methoxytryptamine. 8-OH-DPAT and sumatriptan remained inactive as agonists. 3. In GR127935-treated preparations, methiothepin (3 nM) and mianserin (1 microM), as well as the antipsychotics, clozapine (1 microM), pimozide (300 nM), risperidone (3 nM) and spiperone (1 microM), failed to induce a significant relaxation in prostaglandin F2x-precontracted vessels, but produced significant rightward displacements of the concentration-response curves to 5-HT and 5-CT without significantly reducing the Emax. In a final set of experiments with 5-CT, metergoline (100 nM) and mesulergine (300 nM) behaved as competitive antagonists. In contrast, lisuride (3 nM) noncompetitively antagonized 5-CT-induced relaxation. The estimated affinity (apparent pKa values) of

  17. Advanced commercial tokamak study

    SciTech Connect

    Thomson, S.L.; Dabiri, A.E.; Keeton, D.C.; Brown, T.G.; Bussell, G.T.

    1985-12-01

    Advanced commercial tokamak studies were performed by the Fusion Engineering Design Center (FEDC) as a participant in the Tokamak Power Systems Studies (TPSS) project coordinated by the Office of Fusion Energy. The FEDC studies addressed the issues of tokamak reactor cost, size, and complexity. A scoping study model was developed to determine the effect of beta on tokamak economics, and it was found that a competitive cost of electricity could be achieved at a beta of 10 to 15%. The implications of operating at a beta of up to 25% were also addressed. It was found that the economics of fusion, like those of fission, improve as unit size increases. However, small units were found to be competitive as elements of a multiplex plant, provided that unit cost and maintenance time reductions are realized for the small units. The modular tokamak configuration combined several new approaches to develop a less complex and lower cost reactor. The modular design combines the toroidal field coil with the reactor structure, locates the primary vacuum boundary at the reactor cell wall, and uses a vertical assembly and maintenance approach. 12 refs., 19 figs.

  18. Texas Experimental Tokamak

    SciTech Connect

    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.

  19. Completely bootstrapped tokamak

    SciTech Connect

    Weening, R.H. ); Boozer, A.H. )

    1992-01-01

    Numerical simulations of the evolution of large-scale magnetic fields have been developed using a mean-field Ohm's law. The Ohm's law is coupled to a {Delta}{prime} stabilty analysis and a magnetic island growth equation in order to simulate the behavior of tokamak plasmas that are subject to tearing modes. In one set of calculations, the magnetohydrodynamic (MHD)-stable regime of the tokamak is examined via the construction of an {ital l}{sub {ital i}} -{ital q}{sub {ital a}} diagram. The results confirm previous calculations that show that tearing modes introduce a stability boundary into the {ital l}{sub {ital i}} -{ital q}{sub {ital a}} space. In another series of simulations, the interaction between tearing modes and the bootstrap current is investigated. The results indicate that a completely bootstrapped tokamak may be possible, even in the absence of any externally applied loop voltage or current drive.

  20. ARIES tokamak reactor study

    SciTech Connect

    Steiner, D.; Embrechts, M.

    1990-07-01

    This is a status report on technical progress relative to the tasks identified for the fifth year of Grant No. FG02-85-ER52118. The ARIES tokamak reactor study is a multi-institutional effort to develop several visions of the tokamak as an attractive fusion reactor with enhanced economic, safety, and environmental features. The ARIES study is being coordinated by UCLA and involves a number of institutions, including RPI. The RPI group has been pursuing the following areas of research in the context of the ARIES-I design effort: MHD equilibrium and stability analyses; plasma-edge modeling and blanket materials issues. Progress in these areas is summarized herein.

  1. Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity.

    PubMed

    Ishibashi, Tadashi; Horisawa, Tomoko; Tokuda, Kumiko; Ishiyama, Takeo; Ogasa, Masaaki; Tagashira, Rie; Matsumoto, Kenji; Nishikawa, Hiroyuki; Ueda, Yoko; Toma, Satoko; Oki, Hitomi; Tanno, Norihiko; Saji, Ikutaro; Ito, Akira; Ohno, Yukihiro; Nakamura, Mitsutaka

    2010-07-01

    Lurasidone [(3aR,4S,7R,7aS)-2-[(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylmethyl]hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride; SM-13496] is an azapirone derivative and a novel antipsychotic candidate. The objective of the current studies was to investigate the in vitro and in vivo pharmacological properties of lurasidone. Receptor binding affinities of lurasidone and several antipsychotic drugs were tested under comparable assay conditions using cloned human receptors or membrane fractions prepared from animal tissue. Lurasidone was found to have potent binding affinity for dopamine D(2), 5-hydroxytryptamine 2A (5-HT(2A)), 5-HT(7), 5-HT(1A), and noradrenaline alpha(2C) receptors. Affinity for noradrenaline alpha(1), alpha(2A), and 5-HT(2C) receptors was weak, whereas affinity for histamine H(1) and muscarinic acetylcholine receptors was negligible. In vitro functional assays demonstrated that lurasidone acts as an antagonist at D(2) and 5-HT(7) receptors and as a partial agonist at the 5-HT(1A) receptor subtype. Lurasidone showed potent effects predictive of antipsychotic activity, such as inhibition of methamphetamine-induced hyperactivity and apomorphine-induced stereotyped behavior in rats, similar to other antipsychotics. Furthermore, lurasidone had only weak extrapyramidal effects in rodent models. In animal models of anxiety disorders and depression, treatment with lurasidone was associated with significant improvement. Lurasidone showed a preferential effect on the frontal cortex (versus striatum) in increasing dopamine turnover. Anti-alpha(1)-noradrenergic, anticholinergic, and central nervous system (CNS) depressant actions of lurasidone were also very weak. These results demonstrate that lurasidone possesses antipsychotic activity and antidepressant- or anxiolytic-like effects with potentially reduced liability for extrapyramidal and CNS depressant side effects.

  2. Ex vivo study of 5-HT(1A) and 5-HT(7) receptor agonists and antagonists on cAMP accumulation during memory formation and amnesia.

    PubMed

    Perez-García, G; Meneses, A

    2008-12-16

    The cyclic adenosine monophosphate (cAMP) is a second messenger and a central component of intracellular signaling pathways that regulate a wide range of biological functions, including memory. Hence, in this work, firstly the time-course of memory formation was determined in an autoshaping learning task, which had allowed the identification of testing times for increases or decreases in performance. Next, untrained, trained and overtrained groups were compared in cAMP production. Moreover, selective stimulation and antagonism of 5-HT(1A) and 5-HT(7) receptors during memory formation and cAMP production were determined. Finally, since there is scarce information about how pharmacological models of amnesia affect cAMP production, the cholinergic or glutamatergic antagonists, scopolamine and dizocilpine, were tested. The major findings of this work showed that when the time-course was determined inasmuch as training and testing sessions occurred, memory performance was graduate and progressive. Notably, for the fourth to seventh (i.e., 48-120 h following autoshaping training session) testing session performance was significantly higher from the previous ones. When animals received 5-HT(1A) and 5-HT(7) receptor agonists and antagonists or amnesic drugs significant increases or decrements in memory performance were observed at 24 and 48 h. Moreover, when ex vivo cAMP production from trained and overtrained groups were compared to untrained ones, significant differences were observed among groups and brain areas. Trained animals treated with 8-OHDPAT, AS19, 8-OHDPAT plus AS19, WAY100635, SB-269970, scopolamine or dizocilpine were compared to similar untrained groups, and eightfold-reduced cAMP production was evident, showing the importance of cAMP production in the signaling case in mammalian memory formation.

  3. Activation of 5-HT1A and 5-HT7 receptors in the parafascicular nucleus suppresses the affective reaction of rats to noxious stimulation.

    PubMed

    Harte, Steven E; Kender, Robert G; Borszcz, George S

    2005-02-01

    The antinociceptive effects of the serotonin (5-HT)1A/7 receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) administered into the medial thalamus were evaluated. Pain behaviors organized at spinal (spinal motor reflexes, SMRs), medullary (vocalizations during shock, VDSs), and forebrain (vocalization after discharges, VADs) levels of the neuraxis were elicited by tailshock. Administration of 8-OH-DPAT (5, 10, and 20 microg/side) into nucleus parafascicularis (nPf) produced dose-dependent increases in VDS and VAD thresholds, but failed to elevate SMR threshold. The increase in VAD threshold was significantly greater than that of VDS threshold. Similar effects were observed with administration of 8-OH-DPAT (20 microg/side) into the rostral portion of the central lateral thalamic nucleus. The bilateral or unilateral administration of 8-OH-DPAT (20 microg) into other thalamic nuclei, or into sites dorsal to nPf, did not elevate vocalization thresholds. Increases in vocalization thresholds produced by nPf-administered 8-OH-DPAT were mediated by both 5-HT1A and 5-HT7 receptors. Intra-nPf administration of the 5-HT1A receptor antagonist WAY-100635 (0.05 or 0.5 microg/side), or the 5-HT7 receptor antagonist SB-269970 (1 or 2 microg/side), but not the dopamine D2 receptor antagonist raclopride (10 microg/side), reversed 8-OH-DPAT induced elevations in vocalization thresholds. These results provide the first reported evidence of behavioral antinociception following the administration of a 5-HT agonist into the medial thalamus.

  4. Tearing Modes in Tokamaks

    SciTech Connect

    White, R. B.

    2008-05-14

    This lecture gives a basic introduction to magnetic pound elds, magnetic surface destruction, toroidal equilibrium and tearing modes in a tokamak, including the linear and nonlinear development of these modes and their modi pound cation by current drive and bootstrap current, and sawtooth oscillations and disruptions.

  5. Modular tokamak configuration

    SciTech Connect

    Thomson, S.L.

    1985-01-01

    This report is concerned with the modular tokamak configuration, and presents information on the following topics: modularity; external vacuum boundary; vertical maintenance; combined reactor building/biological shield with totally remote maintenance; independent TF coils; minimum TF coil bore; saddle PF coils; and heat transport system in bore.

  6. Status of the tokamak program

    SciTech Connect

    Sheffield, J.

    1981-06-01

    During the past two decades, the tokamak program has made significant advances. As a result of these advances, the program has expanded, and construction is nearly completed of large facilities, including the US Tokamak Fusion Test Reactor (TFTR), that are capable of achieving energy break-even in the plasma. Design work is under way on the next application phase, exemplified by the US Fusion Engineering Device (FED) and the IAEA INTOR programs. There are many excellent reviews that give a broad history of the evolution of the tokamak program. In addition, reviews are available that give detailed descriptions of individual tokamak elements. This paper reviews the status of the tokamak program, concentrating on recent advances and areas important to the further advancement of the tokamak concept.

  7. Energy confinement in tokamaks

    SciTech Connect

    Sugihara, M.; Singer, C.

    1986-08-01

    A straightforward generalization is made of the ohmic heating energy confinement scalings of Pfeiffer and Waltz and Blackwell et. al. The resulting model is systematically calibrated to published data from limiter tokamaks with ohmic, electron cyclotron, and neutral beam heating. With considerably fewer explicitly adjustable free parameters, this model appears to give a better fit to the available data for limiter discharges than the combined ohmic/auxiliary heating model of Goldston.

  8. TPX tokamak construction management

    SciTech Connect

    Knutson, D.; Kungl, D.; Seidel, P.; Halfast, C.

    1995-12-31

    A construction management contract normally involves the acquisition of a construction management firm to assist in the design, planning, budget conformance, and coordination of the construction effort. In addition the construction management firm acts as an agent in the awarding of lower tier contracts. The TPX Tokamak Construction Management (TCM) approach differs in that the construction management firm is also directly responsible for the assembly and installation of the tokamak including the design and fabrication of all tooling required for assembly. The Systems Integration Support (SIS) contractor is responsible for the architect-engineering design of ancillary systems, such as heating and cooling, buildings, modifications and site improvements, and a variety of electrical requirements, including switchyards and >4kV power distribution. The TCM will be responsible for the procurement of materials and the installation of the ancillary systems, which can either be performed directly by the TCM or subcontracted to a lower tier subcontractor. Assurance that the TPX tokamak is properly assembled and ready for operation when turned over to the operations team is the primary focus of the construction management effort. To accomplish this a disciplined constructability program will be instituted. The constructability effort will involve the effective and timely integration of construction expertise into the planning, component design, and field operations. Although individual component design groups will provide liaison during the machine assembly operations, the construction management team is responsible for assembly.

  9. SER-7, a Caenorhabditis elegans 5-HT7-like Receptor, Is Essential for the 5-HT Stimulation of Pharyngeal Pumping and Egg Laying

    PubMed Central

    Hobson, Robert J.; Hapiak, Vera M.; Xiao, Hong; Buehrer, Kara L.; Komuniecki, Patricia R.; Komuniecki, Richard W.

    2006-01-01

    Serotonin (5-HT) stimulates both pharyngeal pumping and egg laying in Caenorhabditis elegans. Four distinct 5-HT receptors have been partially characterized, but little is known about their function in vivo. SER-7 exhibits most sequence identity to the mammalian 5-HT7 receptors and couples to a stimulation of adenyl cyclase when expressed in COS-7 cells. However, many 5-HT7-specific agonists have low affinity for SER-7. 5-HT fails to stimulate pharyngeal pumping and the firing of the MC motorneurons in animals containing the putative ser-7(tm1325) and ser-7(tm1728) null alleles. In addition, although pumping on bacteria is upregulated in ser-7(tm1325) animals, pumping is more irregular. A similar failure to maintain “fast pumping” on bacteria also was observed in ser-1(ok345) and tph-1(mg280) animals that contain putative null alleles of a 5-HT2-like receptor and tryptophan hydroxylase, respectively, suggesting that serotonergic signaling, although not essential for the upregulation of pumping on bacteria, “fine tunes” the process. 5-HT also fails to stimulate egg laying in ser-7(tm1325), ser-1(ok345), and ser-7(tm1325) ser-1(ok345) animals, but only the ser-7 ser-1 double mutants exhibit an Egl phenotype. All of the SER-7 mutant phenotypes are rescued by the expression of full-length ser-7∷gfp translational fusions. ser-7∷gfp is expressed in several pharyngeal neurons, including the MC, M2, M3, M4, and M5, and in vulval muscle. Interestingly, 5-HT inhibits egg laying and pharyngeal pumping in ser-7 null mutants and the 5-HT inhibition of egg laying, but not pumping, is abolished in ser-7(tm1325);ser-4(ok512) double mutants. Taken together, these results suggest that SER-7 is essential for the 5-HT stimulation of both egg laying and pharyngeal pumping, but that other signaling pathways can probably fulfill similar roles in vivo. PMID:16204223

  10. Differential responses to acute administration of a new 5-HT7-R agonist as a function of adolescent pre-treatment: phMRI and immuno-histochemical study.

    PubMed

    Altabella, Luisa; Sbriccoli, Marco; Zoratto, Francesca; Poleggi, Anna; Vinci, Ramona; Lacivita, Enza; Leopoldo, Marcello; Laviola, Giovanni; Cardone, Franco; Canese, Rossella; Adriani, Walter

    2014-01-01

    LP-211 is a new, selective agonist of serotonin (5-hydroxytryptamine, 5-HT) receptor 7 (5-HT7-R), which is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive and sleep regulation. Adolescent subchronic LP-211 treatment produces some persisting changes in rats' forebrain structural and functional parameters. Here, using pharmacological MRI (phMRI), we investigated the effect of acute administration with LP-211 (10 mg/kg i.p.), or vehicle, to adult rats previously exposed to the same drug (0.25 mg/kg/day for 5 days), or vehicle, during adolescence (44-48 post-natal days); histology and immuno-histochemistry were performed ex vivo to evaluate neuro-anatomical and physiological long-term adaptation to pharmacological pre-treatment. The phMRI signal reveals forebrain areas (i.e., hippocampus, orbital prefrontal cortex), activated in response to LP-211 challenge independently of adolescent pre-treatment. In septum and nucleus accumbens, sensitized activation was found in adolescent pre-treated rats but not in vehicle-exposed controls. Immuno-histochemical analyses showed marked differences in septum as long-term consequence of the adolescent pre-treatment: increased level of 5-HT7-R, increased number of 5-HT7-R positive cells, and enhanced astrocyte activation. For nucleus accumbens, immuno-histochemical analyses did not reveal any difference between adolescent pre-treated rats and vehicle-exposed controls. In conclusion, subchronic LP-211 administration during adolescence is able to induce persistent physiological changes in the septal 5-HT7-R expression and astrocyte response that can still be observed in adulthood. Data shed new insights into roles of 5-HT7-R for normal and pathologic behavioral regulations.

  11. Evaluation of 5-HT7 Receptor Trafficking on In Vivo and In Vitro Model of Lipopolysaccharide (LPS)-Induced Inflammatory Cell Injury in Rats and LPS-Treated A549 Cells.

    PubMed

    Ayaz, Gulsen; Halici, Zekai; Albayrak, Abdulmecit; Karakus, Emre; Cadirci, Elif

    2017-02-01

    This study aimed to investigate the effects of the 5-HT7 receptor agonist (LP44) and antagonist (SB269970) on LPS-induced in vivo tissue damage and cell culture by molecular methods. This study was conducted in two steps. For in vivo studies, 24 female rats were divided into four groups. Group I: healthy; II (2nd h): LPS 5 mg/kg administered intraperitoneally (i.p.); III (4th h): LPS 5 mg/kg administered i.p.; IV (8th h): LPS 5 mg/kg administered i.p. For in vitro studies, we used the A549 cell line. Groups: I control (healthy) (2-4 h); II LPS: 1 µg/ml E. Coli O55:B5 strain (2-4 h); III agonist (LP44) 10(-9) M (2-4 h); IV antagonist (SB269970) 10(-9) M (2-4 h); V LPS+agonist 10(-9) M (LP44 1 µg/ml) (2-4 h); VI LPS+antagonist 10(-9) M (2-4 h). In molecular analyses, we determined increased TNF-α, IL-1β, NF-κB, and 5-HT7 mRNA expressions in rat lung tissues and increased TNF-α, iNOS, and 5-HT7 mRNA expressions in the A549 cell line. In in vitro parameters, LP44 agonist administration-related decrease was observed. Our study showed that lung 5-HT7 receptor expression is increased in LPS-induced endotoxemia. All this data suggest that 5-HT7 receptor overexpression is an important protective mechanism during LPS-induced sepsis-related cell damage.

  12. Structural modifications of the serotonin 5-HT7 receptor agonist N-(4-cyanophenylmethyl)-4-(2-biphenyl)-1-piperazinehexanamide (LP-211) to improve in vitro microsomal stability: A case study.

    PubMed

    Lacivita, Enza; Podlewska, Sabina; Speranza, Luisa; Niso, Mauro; Satała, Grzegorz; Perrone, Roberto; Perrone-Capano, Carla; Bojarski, Andrzej J; Leopoldo, Marcello

    2016-09-14

    The 5-HT7 serotonin receptor is revealing a promising target for innovative therapeutic strategies of neurodevelopmental and neuropsychiatric disorders. Here, we report the synthesis of thirty long-chain arylpiperazine analogs of the selective and brain penetrant 5-HT7 receptor agonist LP-211 (1) designed to enhance stability towards microsomal oxidative metabolism. Commonly used medicinal chemistry strategies were used (i.e., reduction of overall lipophilicity, introduction of electron-withdrawing groups, blocking of potential vulnerable sites of metabolism), and in vitro microsomal stability was tested. The data showed that the adopted design strategy does not directly translate into improvements in stability. Instead, the metabolic stability of the compounds was related to the presence of specific substituents in well-defined regions of the molecule. The collected data allowed for the construction of a machine learning model that, in a given chemical space, is able to describe and quantitatively predict the metabolic stability of the compounds. The majority of the synthesized compounds maintained high affinity for 5-HT7 receptors and showed selectivity towards 5-HT6 and dopamine D2 receptors and different selectivity for 5-HT1A and α1 adrenergic receptors. Compound 50 showed 3-fold higher in vitro stability towards oxidative metabolism than 1 and was able to stimulate neurite outgrowth in neuronal primary cultures through the 5-HT7 receptor in a shorter time and at a lower concentration than the agonist 1. A preliminary disposition study in mice revealed that compound 50 was metabolically stable and was able to pass the blood-brain barrier, thus representing a new tool for studying the pharmacotherapeutic potential of 5-HT7 receptor in vivo.

  13. Differential responses to acute administration of a new 5-HT7-R agonist as a function of adolescent pre-treatment: phMRI and immuno-histochemical study

    PubMed Central

    Altabella, Luisa; Sbriccoli, Marco; Zoratto, Francesca; Poleggi, Anna; Vinci, Ramona; Lacivita, Enza; Leopoldo, Marcello; Laviola, Giovanni; Cardone, Franco; Canese, Rossella; Adriani, Walter

    2014-01-01

    LP-211 is a new, selective agonist of serotonin (5-hydroxytryptamine, 5-HT) receptor 7 (5-HT7-R), which is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive and sleep regulation. Adolescent subchronic LP-211 treatment produces some persisting changes in rats' forebrain structural and functional parameters. Here, using pharmacological MRI (phMRI), we investigated the effect of acute administration with LP-211 (10 mg/kg i.p.), or vehicle, to adult rats previously exposed to the same drug (0.25 mg/kg/day for 5 days), or vehicle, during adolescence (44–48 post-natal days); histology and immuno-histochemistry were performed ex vivo to evaluate neuro-anatomical and physiological long-term adaptation to pharmacological pre-treatment. The phMRI signal reveals forebrain areas (i.e., hippocampus, orbital prefrontal cortex), activated in response to LP-211 challenge independently of adolescent pre-treatment. In septum and nucleus accumbens, sensitized activation was found in adolescent pre-treated rats but not in vehicle-exposed controls. Immuno-histochemical analyses showed marked differences in septum as long-term consequence of the adolescent pre-treatment: increased level of 5-HT7-R, increased number of 5-HT7-R positive cells, and enhanced astrocyte activation. For nucleus accumbens, immuno-histochemical analyses did not reveal any difference between adolescent pre-treated rats and vehicle-exposed controls. In conclusion, subchronic LP-211 administration during adolescence is able to induce persistent physiological changes in the septal 5-HT7-R expression and astrocyte response that can still be observed in adulthood. Data shed new insights into roles of 5-HT7-R for normal and pathologic behavioral regulations. PMID:25565998

  14. Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome

    SciTech Connect

    Gelernter, J.; Rao, P.A.; Pauls, D.L.

    1995-03-20

    A novel serotonin receptor designated 5HT7 (genetic locus HTR7) was cloned in 1993. This receptor has interesting properties related to ligand affinity and CNS distribution that render HTR7 a very interesting candidate gene for neuropsychiatric disorders. We mapped this gene, first by physical methods and then by genetic linkage. First, we made a tentative assignment to chromosome 10, based on hybridization of an HTR7 probe to a Southern blot of DNA from somatic cell hybrids. We then identified a genetic polymorphism at the HTR7 locus. We identified one extended pedigree where the polymorphism segregated. Using the LEPED computer program for pairwise linkage analysis, we confirmed the assignment of the gene to chromosome 10, specifically 10q21-q24, based on a lod score of 5.37 at 0% recombination between HTR7 and D10S20 (a chromosome 10 reference marker). Finally, we excluded genetic linkage between this locus and Tourette syndrome under a reasonable set of assumptions. 15 refs., 1 fig., 1 tab.

  15. An Algorithm to Identify Target-Selective Ligands – A Case Study of 5-HT7/5-HT1A Receptor Selectivity

    PubMed Central

    Kurczab, Rafał; Canale, Vittorio; Zajdel, Paweł; Bojarski, Andrzej J.

    2016-01-01

    A computational procedure to search for selective ligands for structurally related protein targets was developed and verified for serotonergic 5-HT7/5-HT1A receptor ligands. Starting from a set of compounds with annotated activity at both targets (grouped into four classes according to their activity: selective toward each target, not-selective and not-selective but active) and with an additional set of decoys (prepared using DUD methodology), the SVM (Support Vector Machines) models were constructed using a selective subset as positive examples and four remaining classes as negative training examples. Based on these four component models, the consensus classifier was then constructed using a data fusion approach. The combination of two approaches of data representation (molecular fingerprints vs. structural interaction fingerprints), different training set sizes and selection of the best SVM component models for consensus model generation, were evaluated to determine the optimal settings for the developed algorithm. The results showed that consensus models with molecular fingerprints, a larger training set and the selection of component models based on MCC maximization provided the best predictive performance. PMID:27271158

  16. The arylpiperazine derivatives N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide and N-benzyl-4-(2-diphenyl)-1-piperazinehexanamide exert a long-lasting inhibition of human serotonin 5-HT7 receptor binding and cAMP signaling.

    PubMed

    Atanes, Patricio; Lacivita, Enza; Rodríguez, Javier; Brea, José; Burgueño, Javier; Vela, José Miguel; Cadavid, María Isabel; Loza, María Isabel; Leopoldo, Marcello; Castro, Marián

    2013-12-01

    We performed a detailed in vitro pharmacological characterization of two arylpiperazine derivatives, compound N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211) previously identified as a high-affinity brain penetrant ligand for 5-hydroxytryptamine (serotonin) type 7 (5-HT7) receptors, and its analog N-benzyl-4-(2-diphenyl)-1-piperazinehexanamide (MEL-9). Both ligands exhibited competitive displacement of [(3)H]-(2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine ([(3)H]-SB-269970) radioligand binding and insurmountable antagonism of 5-carboxamidotryptamine (5-CT)-stimulated cyclic adenosine monophosphate (cAMP) signaling in human embryonic kidney (HEK293) cells stably expressing human 5-HT7 receptors. They also inhibited forskolin-stimulated adenylate cyclase activity in 5-HT7-expressing HEK293 cells but not in the parental cell line. The compounds elicited long-lasting (at least 24 h) concentration-dependent inhibition of radioligand binding at 5-HT7-binding sites in whole-cell radioligand binding assays, after pretreatment of the cells with the compounds and subsequent compound removal. In cAMP assays, pretreatment of cells with the compounds rendered 5-HT7 receptors unresponsive to 5-CT and also rendered 5-HT7-expressing HEK293 cells unresponsive to forskolin. Compound 1-(2-biphenyl)piperazine (RA-7), a known active metabolite of LP-211 present in vivo, was able to partially inhibit 5-HT7 radioligand binding in a long-lasting irreversible manner. Hence, LP-211 and MEL-9 were identified as high-affinity long-acting inhibitors of human 5-HT7 receptor binding and function in cell lines. The detailed in vitro characterization of these two pharmacological tools targeting 5-HT7 receptors may benefit the study of 5-HT7 receptor function and it may lead to the development of novel selective pharmacological tools with defined functional properties at 5-HT7 receptors.

  17. Magnetic confinement experiment -- 1: Tokamaks

    SciTech Connect

    Goldston, R.J.

    1994-12-31

    This report reviews presentations made at the 15th IAEA Conference on Plasma Physics and Controlled Nuclear Fusion on experimental tokamak physics, particularly on advances in core plasma physics, divertor and edge physics, heating and current drive, and tokamak concept optimization.

  18. Tokamak burn control

    SciTech Connect

    Sager, G.T.

    1988-06-01

    Research of the fusion plasma thermal instability and its control is reviewed. General models of the thermonuclear plasma are developed. Techniques of stability analysis commonly employed in burn control research are discussed. Methods for controlling the plasma against the thermal instability are reviewed. Emphasis is placed on applications to tokamak confinement concepts. Additional research which extends the results of previous research is suggested. Issues specific to the development of control strategies for mid-term engineering test reactors are identified and addressed. 100 refs., 24 figs., 10 tabs.

  19. Mediation of 5-HT-induced external carotid vasodilatation in GR 127935-pretreated vagosympathectomized dogs by the putative 5-HT7 receptor

    PubMed Central

    Villalón, Carlos M; Centurión, David; Luján-Estrada, Miguel; Terrón, José A; Sánchez-López, Araceli

    1997-01-01

    mg kg−1) or ritanserin (100 μg kg−1) plus granisetron (300 μg kg−1), but were dose-dependently blocked by i.v. administration of methiothepin (10 and 30 μg kg−1, given after ritanserin plus granisetron), mesulergine (10 and 30 μg kg−1), metergoline (1 and 3 mg kg−1), methysergide (1 and 3 mg kg−1) or clozapine (0.3 and 1 mg kg−1). Nevertheless, the blockade of the above responses, not significant after treatment with the lower of the two doses of metergoline and mesulergine, was nonspecific after administration of the higher of the two doses of methysergide and clozapine.Based upon the above rank order of agonist potencies and the antagonism produced by a series of drugs showing high affinity for the cloned 5-ht7 receptor, our results indicate that the 5-HT receptor mediating external carotid vasodilatation in GR 127935-pretreated vagosympathectomized dogs is operationally similar to the putative 5-HT7 receptor mediating relaxation of vascular and non-vascular smooth muscles (e.g. rabbit femoral vein, canine coronary artery, rat systemic vasculature and guinea-pig ileum) as well as tachycardia in the cat. PMID:9105708

  20. Selective 5-HT7 Receptor Activation May Enhance Synaptic Plasticity Through N-methyl-D-aspartate (NMDA) Receptor Activity in the Visual Cortex.

    PubMed

    Xiang, Kangjian; Zhao, Xuefei; Li, Youjun; Zheng, Liang; Wang, Jue; Li, Yan-Hai

    2016-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter that modulates N-methyl-D-aspartate (NMDA) receptor activity by binding to several different 5-HT receptor subtypes. In the present study, we used whole-cell patch-clamp recordings in transverse slice preparations to test the role of 5-HT receptors in modulating the NMDA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in layer II/III pyramidal neurons of the rat visual cortex. We found that the NMDA receptor-mediated component of mEPSCs could be potentiated by exogenously applied 5-HT. Similar results were obtained by exogenously applied 5-CT or 8-OH-DPAT (the 5-HT1A and 5-HT7 receptor agonist). A specific antagonist for the 5-HT7 receptor, SB-269970, completely blocked the increase in NMDA receptor-mediated component of mEPSCs by 5-CT or 8- OH-DPAT. Moreover, the selective 5-HT1A receptor antagonist, WAY-100135, displayed no influence on the enhancement in NMDA receptor-mediated component of mEPSCs by 5-CT or 8-OHDPAT. These results indicated that the increase in NMDA receptor-mediated component of mEPSCs by 5-HT in layer II/III pyramidal neurons of the young rat visual cortex requires activation of 5-HT7 receptors, but not 5-HT1A receptors. These observations might be clinically relevant to schizophrenia and Alzheimer's disease (AD), where enhancing NMDA receptor-mediated neurotransmission is considered to be a promising strategy for treatment of these diseases.

  1. Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT1A and 5-HT7 Antagonists in Animal Models

    PubMed Central

    Pytka, Karolina; Partyka, Anna; Jastrzębska-Więsek, Magdalena; Siwek, Agata; Głuch-Lutwin, Monika; Mordyl, Barbara; Kazek, Grzegorz; Rapacz, Anna; Olczyk, Adrian; Gałuszka, Adam; Błachuta, Marian; Waszkielewicz, Anna; Marona, Henryk; Sapa, Jacek; Filipek, Barbara; Wesołowska, Anna

    2015-01-01

    The aim of this study was to further characterize pharmacological properties of two phenylpiperazine derivatives: 1-{2-[2-(2,6-dimethlphenoxy)ethoxy]ethyl}-4-(2-methoxyphenyl)piperazynine hydrochloride (HBK-14) and 2-[2-(2-chloro-6-methylphenoxy)ethoxy]ethyl-4-(2- methoxyphenyl)piperazynine dihydrochloride (HBK-15) in radioligand binding and functional in vitro assays as well as in vivo models. Antidepressant-like properties were investigated in the forced swim test (FST) in mice and rats. Anxiolytic-like activity was evaluated in the four-plate test in mice and elevated plus maze test (EPM) in rats. Imipramine and escitalopram were used as reference drugs in the FST, and diazepam was used as a standard anxiolytic drug in animal models of anxiety. Our results indicate that HBK-14 and HBK-15 possess high or moderate affinity for serotonergic 5-HT2, adrenergic α1, and dopaminergic D2 receptors as well as being full 5-HT1A and 5-HT7 receptor antagonists. We also present their potent antidepressant-like activity (HBK-14—FST mice: 2.5 and 5 mg/kg; FST rats: 5 mg/kg) and (HBK-15—FST mice: 1.25, 2.5 and 5 mg/kg; FST rats: 1.25 and 2.5 mg/kg). We show that HBK-14 (four-plate test: 2.5 and 5 mg/kg; EPM: 2.5 mg/kg) and HBK-15 (four-plate test: 2.5 and 5 mg/kg; EPM: 5 mg/kg) possess anxiolytic-like properties. Among the two, HBK-15 has stronger antidepressant-like properties, and HBK-14 displays greater anxiolytic-like activity. Lastly, we demonstrate the involvement of serotonergic system, particularly 5-HT1A receptor, in the antidepressant- and anxiolytic-like actions of investigated compounds. PMID:26554929

  2. 5-HT2 and 5-HT7 receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons

    PubMed Central

    Sławińska, Urszula; Miazga, Krzysztof; Jordan, Larry M.

    2014-01-01

    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-hydroxy-2-(di-n-propylamino)-tetralin (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 central pattern generator (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

  3. The Tokamak Physics Experiment

    SciTech Connect

    Davidson, R.C.; Goldston, R.J.; Neilson, G.H.; Thomassen, K.I.

    1995-06-01

    The mission of the Tokamak Physics Experiment (TPX) [Nevins {ital et} {ital al}., {ital Plasma} {ital Physics} {ital and} {ital Controlled} {ital Nuclear} {ital Fusion}, Wuerzburg (International Atomic Energy Agency, Vienna, 1992), Vol. 3, p. 279] is to develop the scientific basis for an economically competitive and continuously operating tokamak fusion power source. This complements the primary mission of the International Thermonuclear Experimental Reactor (ITER) [ITER Document Ser. No. 18 (International Atomic Energy Agency, Vienna, 1991)], the demonstration of ignition and long-pulse burn, and the integration of nuclear technologies. The TPX program is focused on making the demonstration power plant that follows ITER as compact and attractive as possible, and on permitting ITER to achieve its ultimate goal of steady-state operation. This mission of TPX requires the development of steady-state regimes with high beta, good confinement, and a high fraction of a self-driven bootstrap current. These regimes must be compatible with plasma stability, strong heat-flux dispersion in the divertor region, and effective particle control.

  4. The Tokamak Physics Experiment

    NASA Astrophysics Data System (ADS)

    Davidson, Ronald C.; Goldston, Robert J.; Neilson, George H.; Thomassen, Keith I.

    1995-06-01

    The mission of the Tokamak Physics Experiment (TPX) [Nevins et al., Plasma Physics and Controlled Nuclear Fusion, Würzburg (International Atomic Energy Agency, Vienna, 1992), Vol. 3, p. 279] is to develop the scientific basis for an economically competitive and continuously operating tokamak fusion power source. This complements the primary mission of the International Thermonuclear Experimental Reactor (ITER) [ITER Document Ser. No. 18 (International Atomic Energy Agency, Vienna, 1991)], the demonstration of ignition and long-pulse burn, and the integration of nuclear technologies. The TPX program is focused on making the demonstration power plant that follows ITER as compact and attractive as possible, and on permitting ITER to achieve its ultimate goal of steady-state operation. This mission of TPX requires the development of steady-state regimes with high beta, good confinement, and a high fraction of a self-driven bootstrap current. These regimes must be compatible with plasma stability, strong heat-flux dispersion in the divertor region, and effective particle control.

  5. Edge turbulence in tokamaks

    NASA Astrophysics Data System (ADS)

    Nedospasov, A. V.

    1992-12-01

    Edge turbulence is of decisive importance for the distribution of particle and energy fluxes to the walls of tokamaks. Despite the availability of extensive experimental data on the turbulence properties, its nature still remains a subject for discussion. This paper contains a review of the most recent theoretical and experimental studies in the field, including mainly the studies to which Wootton (A.J. Wooton, J. Nucl. Mater. 176 & 177 (1990) 77) referred to most in his review at PSI-9 and those published later. The available theoretical models of edge turbulence with volume dissipation due to collisions fail to fully interpret the entire combination of experimental facts. In the scrape-off layer of a tokamak the dissipation prevails due to the flow of current through potential shifts near the surface of limiters of divertor plates. The different origins of turbulence at the edge and in the core plasma due to such dissipation are discussed in this paper. Recent data on the electron temperature fluctuations enabled one to evaluate the electric probe measurements of turbulent flows of particles and heat critically. The latest data on the suppression of turbulence in the case of L-H transitions are given. In doing so, the possibility of exciting current instabilities in biasing experiments (rather than only to the suppression of existing turbulence) is given some attention. Possible objectives of further studies are also discussed.

  6. Tokamak building-design considerations for a large tokamak device

    SciTech Connect

    Barrett, R.J.; Thomson, S.L.

    1981-01-01

    Design and construction of a satisfactory tokamak building to support FED appears feasible. Further, a pressure vessel building does not appear necessary to meet the plant safety requirements. Some of the building functions will require safety class systems to assure reliable and safe operation. A rectangular tokamak building has been selected for FED preconceptual design which will be part of the confinement system relying on ventilation and other design features to reduce the consequences and probability of radioactivity release.

  7. Solid-Supported Synthesis and 5-HT7 /5-HT1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5-dihydro-1,2,4-triazine-6-(1H)-one.

    PubMed

    Grychowska, Katarzyna; Masurier, Nicolas; Verdié, Pascal; Satała, Grzegorz; Bojarski, Andrzej J; Martinez, Jean; Pawłowski, Maciej; Subra, Gilles; Zajdel, Paweł

    2015-10-01

    A series of arylpiperazinylbutyl derivatives of 4,5-dihydro-1,2,4-triazine-6(1H)-ones was designed and synthesized according to the new solid-supported methodology. In this approach, triazinone scaffold was constructed from the Fmoc-protected glycine. The library representatives showed different levels of affinity for 5-HT7 and 5-HT1A receptors; compounds 13, 14 and 18-20 were classified as dual 5-HT7 /5-HT1A receptors ligands. The structure-affinity relationship analysis revealed that the receptor affinity and selectivity of the tested compounds depended on the kind of substituent in position 3 of triazinone fragment as well as substitution pattern of the phenylpiperazine moiety.

  8. Causes of major tokamak disruptions

    SciTech Connect

    White, R.B.; Monticello, D.A.

    1980-07-01

    The nonlinear saturation theory of the tearing mode is used to examine the necessary conditions for the occurrence of a major tokamak disruption. The results are compared with full three-dimensional numerical simulations, and with experimental data.

  9. Review: 5-Ht1, 5-Ht2, 5-Ht3, And 5-Ht7 Receptors And Their Role In The Modulation Of Pain Response In The Central Nervous System.

    PubMed

    Cortes-Altamirano, José Luis; Olmos-Hernández, Adriana; Bonilla-Jaime, Herlinda; Carrillo-Mora, Paul; Bandala, Cindy; Reyes-Long, S; Alfaro-Rodríguez, Alfonso

    2017-09-11

    The aim of this review was to identify the mechanisms by which serotonin receptors involved at the central level are able to modulate the nociceptive response. Pain is a defense mechanism of the body that entails physiological, anatomical, neurochemical, and psychological changes, and is defined as an unpleasant sensory and emotional experience with potential risk of tissue damage, comprising the leading cause of appointments with Physicians worldwide. Treatment for this symptom has generated several neuropharmacological lines of research, due to the different types of pain and the various drugs employed to treat this condition. Serotonin [5-HydroxyTryptamine (5-HT)] is a neurotransmitter with seven families (5-HT1–5-HT7) and approximately 15 receptor subtypes. Serotonin modulates neuronal activity; however, this neurotransmitter is related with a number of physiological processes, such as cardiovascular function, gastric motility, renal function, etc. On the other hand, several researches reported that serotonin modulates nociceptive response through 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the Central Nervous System (CNS). In this review, a search was conducted on PubMed, ProQuest, EBSCO, and the Science Citation Index for studies evaluating the effects of 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS on the modulation of different types of pain. Conclusions We concluded that 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS modulate the pain, but this depends on the distribution of the receptors, dose of agonists or antagonists, administration route, pain type and duration to order to inhibit, to excite, or even maintain the nociceptive response. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. New N- and O-arylpiperazinylalkyl pyrimidines and 2-methylquinazolines derivatives as 5-HT7 and 5-HT1A receptor ligands: Synthesis, structure-activity relationships, and molecular modeling studies.

    PubMed

    Intagliata, Sebastiano; Modica, Maria N; Pittalà, Valeria; Salerno, Loredana; Siracusa, Maria A; Cagnotto, Alfredo; Salmona, Mario; Kurczab, Rafał; Romeo, Giuseppe

    2017-02-01

    Based on our earlier studies of structure activity relationships on 4-substituted piperazine derivatives, in this work we synthesized a novel set of long-chain arylpiperazines with the purpose of elucidating if some structural modifications in the terminal fragment could affect the binding affinity for the 5-HT7 and 5-HT1A receptors. In this new series, the quinazolinone system of the previous derivatives was replaced by a 6-phenylpyrimidine or a 2-methylquinazoline, which were used as versatile building blocks for the preparation of new compounds. A 4-arylpiperazine moiety through a five methylene chain was anchored at the nitrogen or oxygen atom of the heterocyclic scaffolds. The substituents borne by the piperazine nucleus were phenyl, phenylmethyl, 3- or 4-chlorophenyl, and 2-ethoxyphenyl. Binding tests, performed on human cloned 5-HT7 and 5-HT1A receptors, showed that, among the newly synthesized derivatives, 4-[5-[4-(2-ethoxyphenyl)-1-piperazinyl]pentoxy]-6-phenyl-pyrimidine (13) and 3-[5-[4-(2-ethoxyphenyl)-1-piperazinyl]pentyl]-2-methyl-4(3H)-quinazolinone (20) displayed the best affinity values, Ki=23.5 and 8.42nM for 5-HT7 and 6.96 and 2.99nM for 5-HT1A receptors, respectively. Moreover, the functional properties for both compounds were further evaluated using the cAMP assay. Finally, a molecular modeling study has been performed for 5-HT7 and 5-HT1A receptor homology models to investigate the binding mode of N- and O-alkylated pyrimidinones/pyrimidines 4-13, 2-methylquinazolinones/quinazolines 17-22, and previously reported 2- and 3-substituted quinazolinones 23-30.

  11. Bootstrap current in a tokamak

    SciTech Connect

    Kessel, C.E.

    1994-03-01

    The bootstrap current in a tokamak is examined by implementing the Hirshman-Sigmar model and comparing the predicted current profiles with those from two popular approximations. The dependences of the bootstrap current profile on the plasma properties are illustrated. The implications for steady state tokamaks are presented through two constraints; the pressure profile must be peaked and {beta}{sub p} must be kept below a critical value.

  12. The Thor tokamak experiment

    NASA Astrophysics Data System (ADS)

    Argenti, L.; Bonizzoni, G.; Cirant, S.; Corti, S.; Grosso, G.; Lampis, G.; Rossi, L.; Carretta, U.; Jacchia, A.; de Luca, F.

    1981-06-01

    The principle characteristics of plasma discharges produced in Thor tokamak experiments are discussed. The equilibrium and stability characteristics of the plasma produced are considered, with attention given to the density limits and critical streaming parameter for stable operation. The temporal evolution of the main plasma parameters, including electron density, electron temperature distribution, hard X-ray emission from suprathermal electrons, neutral gas influx, plasma density and Ohmic heating efficiency, is then examined, with particular emphasis on means used to control the electron runaway. The results achieved are noted to have demonstrated the possibility of controlling both plasma equilibrium and discharge regime, and further improvements expected by the use of more efficient preionization, gas puffing and feedback poloidal control of column position are indicated.

  13. Filamentation in tokamaks

    SciTech Connect

    Cardozo, N.J.; Barth, C.J.; Chu, C.C.; Lok, J.; Montvai, A.; Oomens, A.A.; Peters, M.; Pijper, F.J.; de Rover, M.; Schueller, F.C.; Steenbakkers, M.F.; RTP team

    1995-09-01

    The relevance of a nest of toroidal flux surfaces as a paradigm of the magnetic topology of a tokamak plasma is challenged. High resolution Thomson scattering measurements of electron temperature and density in RTP show several hot filaments in the plasma center and sharp gradients near the sawtooth inversion radius and structures outside the sawtooth region under central ECH. In ohmic plasmas, too, the pressure and temperature profiles show significant bumps. These measurements give evidence of a complex magnetic topology. Transport in a medium with spatially strongly varying diffusivity is considered. It is shown that macroscopic transport is determined by the microscopic structure: a transport theory must predict this structure and the diffusivity in the insulating regions, while the {open_quote}turbulent{close_quote} diffusivity is irrelevant. A numerical approach to equilibria with broken surfaces is presented. {copyright} {ital 1995 American Institute of Physics.}

  14. The ARIES tokamak reactor study

    SciTech Connect

    Not Available

    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{sup 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.

  15. Locomotor-activated neurons of the cat. I. Serotonergic innervation and co-localization of 5-HT7, 5-HT2A, and 5-HT1A receptors in the thoraco-lumbar spinal cord.

    PubMed

    Noga, Brian R; Johnson, Dawn M G; Riesgo, Mirta I; Pinzon, Alberto

    2009-09-01

    Monoamines are strong modulators and/or activators of spinal locomotor networks. Thus monoaminergic fibers likely contact neurons involved in generating locomotion. The aim of the present study was to investigate the serotonergic innervation of locomotor-activated neurons within the thoraco-lumbar spinal cord following induction of hindlimb locomotion. This was determined by immunohistochemical co-localization of serotonin (5-HT) fibers or 5-HT(7)/5-HT2A/5-HT1A receptors with cells expressing the activity-dependent marker c-fos. Experiments were performed on paralyzed, decerebrate cats in which locomotion was induced by electrical stimulation of the mesencephalic locomotor region. Abundant c-fos immunoreactive cells were observed in laminae VII and VIII throughout the thoraco-lumbar segments of locomotor animals. Control sections from the same segments showed significantly fewer labeled neurons, mostly within the dorsal horn. Multiple serotonergic boutons were found in close apposition to the majority (80-100%) of locomotor cells, which were most abundant in lumbar segments L3-7. 5-HT7 receptor immunoreactivity was observed on cells across the thoraco-lumbar segments (T7-L7), in a dorsoventral gradient. Most locomotor-activated cells co-localized with 5-HT7, 5-HT2A, and 5-HT1A receptors, with largest numbers in laminae VII and VIII. Co-localization of c-fos and 5-HT7 receptor was highest in the L5-L7 segments (>90%) and decreased rostrally (to approximately 50%) due to the absence of receptors on cells within the intermediolateral nucleus. In contrast, 60-80 and 35-80% of c-fos immunoreactive cells stained positive for 5-HT2A and 5-HT1A receptors, respectively, with no rostrocaudal gradient. These results indicate that serotonergic modulation of locomotion likely involves 5-HT(7)/5-HT2A/5-HT1A receptors located on the soma and proximal dendrites of serotonergic-innervated locomotor-activated neurons within laminae VII and VIII of thoraco-lumbar segments.

  16. Locomotor-Activated Neurons of the Cat. I. Serotonergic Innervation and Co-Localization of 5-HT7, 5-HT2A, and 5-HT1A Receptors in the Thoraco-Lumbar Spinal Cord

    PubMed Central

    Noga, Brian R.; Johnson, Dawn M. G.; Riesgo, Mirta I.; Pinzon, Alberto

    2009-01-01

    Monoamines are strong modulators and/or activators of spinal locomotor networks. Thus monoaminergic fibers likely contact neurons involved in generating locomotion. The aim of the present study was to investigate the serotonergic innervation of locomotor-activated neurons within the thoraco-lumbar spinal cord following induction of hindlimb locomotion. This was determined by immunohistochemical co-localization of serotonin (5-HT) fibers or 5-HT7/5-HT2A/5-HT1A receptors with cells expressing the activity-dependent marker c-fos. Experiments were performed on paralyzed, decerebrate cats in which locomotion was induced by electrical stimulation of the mesencephalic locomotor region. Abundant c-fos immunoreactive cells were observed in laminae VII and VIII throughout the thoraco-lumbar segments of locomotor animals. Control sections from the same segments showed significantly fewer labeled neurons, mostly within the dorsal horn. Multiple serotonergic boutons were found in close apposition to the majority (80–100%) of locomotor cells, which were most abundant in lumbar segments L3–7. 5-HT7 receptor immunoreactivity was observed on cells across the thoraco-lumbar segments (T7–L7), in a dorsoventral gradient. Most locomotor-activated cells co-localized with 5-HT7, 5-HT2A, and 5-HT1A receptors, with largest numbers in laminae VII and VIII. Co-localization of c-fos and 5-HT7 receptor was highest in the L5–L7 segments (>90%) and decreased rostrally (to ∼50%) due to the absence of receptors on cells within the intermediolateral nucleus. In contrast, 60–80 and 35–80% of c-fos immunoreactive cells stained positive for 5-HT2A and 5-HT1A receptors, respectively, with no rostrocaudal gradient. These results indicate that serotonergic modulation of locomotion likely involves 5-HT7/5-HT2A/5-HT1A receptors located on the soma and proximal dendrites of serotonergic-innervated locomotor-activated neurons within laminae VII and VIII of thoraco-lumbar segments. PMID:19571190

  17. Bibliography of fusion product physics in tokamaks

    SciTech Connect

    Hively, L. M.; Sigmar, D. J.

    1989-09-01

    Almost 700 citations have been compiled as the first step in reviewing the recent research on tokamak fusion product effects in tokamaks. The publications are listed alphabetically by the last name of the first author and by subject category.

  18. Moving Divertor Plates in a Tokamak

    SciTech Connect

    S.J. Zweben, H. Zhang

    2009-02-12

    Moving divertor plates could help solve some of the problems of the tokamak divertor through mechanical ingenuity rather than plasma physics. These plates would be passively heated on each pass through the tokamak and cooled and reprocessed outside the tokamak. There are many design options using varying plate shapes, orientations, motions, coatings, and compositions.

  19. Tokamak Physics Experiment (TPX) design

    SciTech Connect

    Schmidt, J.A.

    1995-12-31

    TPX is a national project involving a large number of US fusion laboratories, universities, and industries. The element of the TPX requirements that is a primary driver for the hardware design is the fact that TPX tokamak hardware is being designed to accommodate steady state operation if the external systems are upgraded from the 1,000 second initial operation. TPX not only incorporates new physics, but also pioneers new technologies to be used in ITER and other future reactors. TPX will be the first tokamak with fully superconducting magnetic field coils using advanced conductors, will have internal nuclear shielding, will use robotics for machine maintenance, and will remove the continuous, concentrated heat flow from the plasma with new dispersal techniques and with special materials that are actively cooled. The Conceptual Design for TPX was completed during Fiscal Year 1993. The Preliminary Design formally began at the beginning of Fiscal Year 1994. Industrial contracts have been awarded for the design, with options for fabrication, of the primary tokamak hardware. A large fraction of the design and R and D effort during FY94 was focused on the tokamak and in turn on the tokamak magnets. The reason for this emphasis is because the magnets require a large design and R and D effort, and are critical to the project schedule. The magnet development is focused on conductor development, quench protection, and manufacturing R and D. The Preliminary Design Review for the Magnets is planned for fall, 1995.

  20. Resistive instabilities in tokamaks

    SciTech Connect

    Rutherford, P.H.

    1985-10-01

    Low-m tearing modes constitute the dominant instability problem in present-day tokamaks. In this lecture, the stability criteria for representative current profiles with q(0)-values slightly less than unit are reviewed; ''sawtooth'' reconnection to q(0)-values just at, or slightly exceeding, unity is generally destabilizing to the m = 2, n = 1 and m = 3, n = 2 modes, and severely limits the range of stable profile shapes. Feedback stabilization of m greater than or equal to 2 modes by rf heating or current drive, applied locally at the magnetic islands, appears feasible; feedback by island current drive is much more efficient, in terms of the radio-frequency power required, then feedback by island heating. Feedback stabilization of the m = 1 mode - although yielding particularly beneficial effects for resistive-tearing and high-beta stability by allowing q(0)-values substantially below unity - is more problematical, unless the m = 1 ideal-MHD mode can be made positively stable by strong triangular shaping of the central flux surfaces. Feedback techniques require a detectable, rotating MHD-like signal; the slowing of mode rotation - or the excitation of non-rotating modes - by an imperfectly conducting wall is also discussed.

  1. Status of tokamak experiments

    SciTech Connect

    Wolf, G.H.

    1996-03-01

    Plasma-wall interaction, heat removal and ash exhaust have emerged as the dominant problems still to be solved in order to achieve ignition and - even more difficult - to maintain a state of self-sustained thermo-nuclear burn. This is of particular delicacy, since those operational regimes which yield the best energy confinement correspond to an even better particle confinement and confinement of impurities, which then tend to accumulate in the plasma core and to result in disruption or degradation of the tokamak discharge. Therefore, plasma-wall interaction, heat removal and particle exhaust will determine not only the structure and configuration of the plasma edge region, of the wall system and of the materials facing the plasma, but also the final choice of useful confinement regimes. Moreover, the potential effect of powerful {alpha}-particle heating on plasma stability and confinement has to be kept below critical values. For the latter requirement, a final answer can only be obtained in an ITER-type device where ignition and burn will become accessible. 72 refs., 12 figs.

  2. Summary discussion: An integrated advanced tokamak reactor

    SciTech Connect

    Sauthoff, N.R.

    1994-12-31

    The tokamak concept improvement workshop addressed a wide range of issues involved in the development of a more attractive tokamak. The agenda for the workshop progressed from a general discussion of the long-range energy context (with the objective being the identification of a set of criteria and ``figures of merit`` for measuring the attractiveness of a tokamak concept) to particular opportunities for the improvement of the tokamak concept. The discussions concluded with a compilation of research program elements leading to an improved tokamak concept.

  3. Understanding disruptions in tokamaks

    NASA Astrophysics Data System (ADS)

    Zakharov, Leonid

    2011-10-01

    Disruptions in tokamaks are known since 1963 but even now some aspects of them remain a mystery. This talk describes progress made recently in understanding disruptions. A major step forward occurred in 2007 when the importance of galvanic contact of the plasma with the wall in plasma dynamics was pointed out. The toroidal asymmetry of plasma current, observed in JET vertical disruptions, was explained by the theory of the wall touching kink mode. The currents shared by the plasma with the wall and responsible for the asymmetry were identified as generated by the kink mode. Such currents are referred to as Hiro currents. They have shown exceptional consistency with the entire JET disruption data base (more than 5500 cases) and ruled out the long lasting interpretation based on ``halo currents,'' which contradict experiments even in the sign of the measured asymmetry. Accordingly, the sideways forces are understood and their scaling from JET to ITER was justified. Hiro currents provide also a plausible explanation of the current spike at the beginning of the disruptions. The important role of the plasma edge and its interaction with the wall was revealed. Based on this new understanding of disruptions, dedicated experiments on the current spike (J-TEXT, Wuhan, China) and runaway prevention by the repetitive triggering of kink modes (T-10, AUG, Tore Supra) were motivated and are in progress. Accordingly, the need for new, adaptive grid approaches to numerical simulations of disruptions became evident. In addition to the core MHD, simulations of realistic wall geometry, disruption specific plasma edge physics, plasma-wall interaction, and energetic particles need be developed. The first results of simulations of the fast MHD regime, Hiro current generation, and slower plasma decay due to a wall touching kink mode made with the new DSC code are presented. This work is supported by US DoE contract No. DE-AC02-09-CH11466.

  4. An enhanced tokamak startup model

    NASA Astrophysics Data System (ADS)

    Goswami, Rajiv; Artaud, Jean-François

    2017-01-01

    The startup of tokamaks has been examined in the past in varying degree of detail. This phase typically involves the burnthrough of impurities and the subsequent rampup of plasma current. A zero-dimensional (0D) model is most widely used where the time evolution of volume averaged quantities determines the detailed balance between the input and loss of particle and power. But, being a 0D setup, these studies do not take into consideration the co-evolution of plasma size and shape, and instead assume an unchanging minor and major radius. However, it is known that the plasma position and its minor radius can change appreciably as the plasma evolves in time to fill in the entire available volume. In this paper, an enhanced model for the tokamak startup is introduced, which for the first time takes into account the evolution of plasma geometry during this brief but highly dynamic period by including realistic one-dimensional (1D) effects within the broad 0D framework. In addition the effect of runaway electrons (REs) has also been incorporated. The paper demonstrates that the inclusion of plasma cross section evolution in conjunction with REs plays an important role in the formation and development of tokamak startup. The model is benchmarked against experimental results from ADITYA tokamak.

  5. Prospects for Tokamak Fusion Reactors

    SciTech Connect

    Sheffield, J.; Galambos, J.

    1995-04-01

    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.

  6. Tokamak and RFP ignition requirements

    SciTech Connect

    Werley, K.A.

    1991-01-01

    A plasma model is applied to calculate numerically transport- confinement (n{tau}{sub E}) requirements and steady-state operation tokamak. The CIT tokamak and RFP ignition conditions are examined. Physics differences between RFP and tokamaks, and their consequences for a DT ignition machine, are discussed. The ignition RFP, compared to a tokamak, has many physics advantages, including ohmic heating to ignition (no need for auxiliary heating systems), higher beta, low ignition current, less sensitivity of ignition requirements to impurity effects, no hard disruptions (associated with beta or density limits), and successful operation with high radiation fractions (f{sub RAD} {approximately} 0.95). These physics advantages, coupled with important engineering advantages associated with lower external magnetic fields, larger aspect ratios, and smaller plasma cross sections translate into significant cost reductions for both ignition and power reactor. The primary drawback of the RFP is the uncertainty that the present confinement scaling will extrapolate to reactor regimes. The 4-MA ZTH was expected to extend the n{tau}{sub E} transport scaling data three order of magnitude above ZT-40M results, and if the present scaling held, to achieve a DT-equivalent scientific energy breakeven, Q=1. A basecase RFP ignition point is identified with a plasma current of 8.1 MA and no auxiliary heating. 16 refs., 4 figs., 1 tab.

  7. High Energy Particles in Tokamaks

    SciTech Connect

    White, R. B.

    2008-05-14

    This lecture covers the derivation of guiding center equations in a tokamak, orbit classification, the effect of magnetic perturbations and ripple, the interaction of particles with magnetohydrodynamic modes, including passing particle resonance, toroidal Alfven mode drive and saturation, the fishbone mode, and sawtooth stabilization.

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

    SciTech Connect

    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.

    2013-08-15

    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.

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

    PubMed

    Yang, J H; Yang, X F; 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

    2013-08-01

    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.

  10. Bootstrapped tokamak with oscillating field current drive

    SciTech Connect

    Weening, R.H. )

    1993-07-01

    A magnetic helicity conserving mean-field Ohm's law is used to study bootstrapped tokamaks with oscillating field current drive. The Ohm's law leads to the conclusion that the tokamak bootstrap effect can convert the largely alternating current of oscillating field current drive into a direct toroidal plasma current. This plasma current rectification is due to the intrinsically nonlinear nature of the tokamak bootstrap effect, and suggests that it may be possible to maintain the toroidal current of a tokamak reactor by supplementing the bootstrap current with oscillating field current drive. Steady-state tokamak fusion reactors operating with oscillating field current drive could provide an alternative to tokamak reactors operating with external current drive.

  11. Cryogenic needs for future tokamaks

    NASA Astrophysics Data System (ADS)

    Katheder, H.

    The ITER tokamak is a machine using superconducting magnets. The windings of these magnets will be subjected to high heat loads resulting from a combination of nuclear energy absorption and AC-losses. It is estimated that about 100 kW at 4.5 K are needed. The total cooling mass flow rate will be around 10 - 15 kg/s. In addition to the large cryogenic power required for the superconducting magnets cryogenic power is also needed for refrigerated radiation shield, various cryopumps, fuel processing and test beds. A general description of the overall layout and the envisaged refrigerator cycle, necessary cold pumps and ancillary equipment is given. The basic cryogenic layout for the ITER tokakmak design, as developed during the conceptual design phase and a short overview about existing tokamak designs using superconducting magnets is given.

  12. Options for an ignited tokamak

    SciTech Connect

    Sheffield, J.

    1984-02-01

    It is expected that the next phase of the fusion program will involve a tokamak with the goals of providing an ignited plasma for pulses of hundreds of seconds. A simple model is described in this memorandum which establishes the physics conditions for such a self-sustaining plasma, for given ion and electron thermal diffusivities, in terms of R/a, b/a, I, B/q, epsilon ..beta../sub p/, anti T/sub i/, and anti T/sub e//anti T/sub i/. The model is used to produce plots showing the wide range of tokamaks that may ignite or have a given ignition margin. The constraints that limit this range are discussed.

  13. Folded waveguide designs for tokamaks

    NASA Astrophysics Data System (ADS)

    Hoffman, D. J.; Bigelow, T. S.; Fogelman, C. H.; Yugo, J. J.; Caughman, J. B. O.; Gardner, W. L.; Carter, M. D.; Probert, P. H.; Barbato, E.

    The folded waveguide (FWG) has been tested to the megawatt level in RFTF and shows great promise for tokamak use. It has three primary advantages: low electric field (anywhere) per unit power coupled to the plasma, strong structural capabilities, and better spectral content than loops. A tokamak test is now needed. Potential candidates include C-Mod at 80 MHz and FTU at 433 MHz. The waveguide test on the first machine will be directed at conventional ion cyclotron heating, while the test on the latter will be directed at direct electron heating. In addition, a variation of the folded waveguide is proposed to be tested on Phaedrus-T. In this paper, we discuss the advantages of the waveguide, the design layout, some of the potential physics programs, and how these programs may have an impact on its potential use in ITER.

  14. Neoclassical magnetic microislands in tokamaks

    SciTech Connect

    Kovalishen, E.A.; Mikhailovskii, A.B.; Botov, P.V.; Shirokov, M.S.; Konovalov, S.V.; Tsypin, V.S.; Galvao, R.M.O.

    2005-09-15

    Possibility of existence of neoclassical magnetic microislands (island width smaller than the ion Larmor radius) in a tokamak in the banana regime is shown. The rotation frequency of such islands is found. It is shown that for the case of positive electron temperature gradient, the bootstrap current destabilizes the microislands while the polarization current leads to their stabilization. Maximally possible neoclassical microisland width is estimated.

  15. Transport Equations In Tokamak Plasmas

    NASA Astrophysics Data System (ADS)

    Callen, J. D.

    2009-11-01

    Tokamak plasma transport equations are usually obtained by flux surface averaging the collisional Braginskii equations. However, tokamak plasmas are not in collisional regimes. Also, ad hoc terms are added for: neoclassical effects on the parallel Ohm's law (trapped particle effects on resistivity, bootstrap current); fluctuation-induced transport; heating, current-drive and flow sources and sinks; small B field non-axisymmetries; magnetic field transients etc. A set of self-consistent second order in gyroradius fluid-moment-based transport equations for nearly axisymmetric tokamak plasmas has been developed recently using a kinetic-based framework. The derivation uses neoclassical-based parallel viscous force closures, and includes all the effects noted above. Plasma processes on successive time scales (and constraints they impose) are considered sequentially: compressional Alfv'en waves (Grad-Shafranov equilibrium, ion radial force balance); sound waves (pressure constant along field lines, incompressible flows within a flux surface); and ion collisions (damping of poloidal flow). Radial particle fluxes are driven by the many second order in gyroradius toroidal angular torques on the plasma fluid: 7 ambipolar collision-based ones (classical, neoclassical, etc.) and 8 non-ambipolar ones (fluctuation-induced, polarization flows from toroidal rotation transients etc.). The plasma toroidal rotation equation [1] results from setting to zero the net radial current induced by the non-ambipolar fluxes. The radial particle flux consists of the collision-based intrinsically ambipolar fluxes plus the non-ambipolar fluxes evaluated at the ambipolarity-enforcing toroidal plasma rotation (radial electric field). The energy transport equations do not involve an ambipolar constraint and hence are more directly obtained. The resultant transport equations will be presented and contrasted with the usual ones. [4pt] [1] J.D. Callen, A.J. Cole, C.C. Hegna, ``Toroidal Rotation In

  16. Magnetic island formation in tokamaks

    SciTech Connect

    Yoshikawa, S.

    1989-04-01

    The size of a magnetic island created by a perturbing helical field in a tokamak is estimated. A helical equilibrium of a current- carrying plasma is found in a helical coordinate and the helically flowing current in the cylinder that borders the plasma is calculated. From that solution, it is concluded that the helical perturbation of /approximately/10/sup /minus/4/ of the total plasma current is sufficient to cause an island width of approximately 5% of the plasma radius. 6 refs.

  17. Equilibrium Reconstruction in EAST Tokamak

    NASA Astrophysics Data System (ADS)

    Qian, Jinping; Wan, Baonian; L. Lao, L.; Shen, Biao; A. Sabbagh, S.; Sun, Youwen; Liu, Dongmei; Xiao, Bingjia; Ren, Qilong; Gong, Xianzu; Li, Jiangang

    2009-04-01

    Reconstruction of experimental axisymmetric equilibria is an important part of tokamak data analysis. Fourier expansion is applied to reconstruct the vessel current distribution in EFIT code. Benchmarking and testing calculations are performed to evaluate and validate this algorithm. Two cases for circular and non-circular plasma discharges are presented. Fourier expansion used to fit the eddy current is a robust method and the real time EFIT can be introduced to the plasma control system in the coming campaign.

  18. Magnetic confinement experiment. I: Tokamaks

    SciTech Connect

    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 nT{tau}`s {approximately} 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.

  19. 5-HT1A/1B, 5-HT6, and 5-HT7 serotonergic receptors recruitment in tonic-clonic seizure-induced antinociception: role of dorsal raphe nucleus.

    PubMed

    Freitas, Renato Leonardo; Ferreira, Célio Marcos dos Reis; Urbina, Maria Angélica Castiblanco; Mariño, Andrés Uribe; Carvalho, Andressa Daiane; Butera, Giuseppe; de Oliveira, Ana Maria; Coimbra, Norberto Cysne

    2009-05-01

    Pharmacological studies have been focused on the involvement of different neural pathways in the organization of antinociception that follows tonic-clonic seizures, including 5-hydroxytryptamine (5-HT)-, norepinephrine-, acetylcholine- and endogenous opioid peptide-mediated mechanisms, giving rise to more in-depth comprehension of this interesting post-ictal antinociceptive phenomenon. The present work investigated the involvement of 5-HT(1A/1B), 5-HT(6), and 5-HT(7) serotonergic receptors through peripheral pretreatment with methiothepin at doses of 0.5, 1.0, 2.0 and 3.0 mg/kg in the organization of the post-ictal antinociception elicited by pharmacologically (with pentylenetetrazole at 64 mg/kg)-induced tonic-clonic seizures. Methiothepin at 1.0 mg/kg blocked the post-ictal antinociception recorded after the end of seizures, whereas doses of 2.0 and 3.0 mg/kg potentiated the post-ictal antinociception. The nociceptive thresholds were kept higher than those of the control group. However, when the same 5-hydroxytryptamine receptors antagonist was microinjected (at 1.0, 3.0 and 5.0 microg/0.2 microL) in the dorsal raphe nucleus, a mesencephalic structure rich in serotonergic neurons and 5-HT receptors, the post-ictal hypo-analgesia was consistently antagonized. The present findings suggest a dual effect of methiothepin, characterized by a disinhibitory effect on the post-ictal antinociception when peripherally administered (possibly due to an antagonism of pre-synaptic 5-HT(1A) serotonergic autoreceptors in the pain endogenous inhibitory system) and an inhibitory effect (possibly due to a DRN post-synaptic 5-HT(1B), 5-HT(6), and 5-HT(7) serotonergic receptors blockade) when centrally administered. The present data also suggest that serotonin-mediated mechanisms of the dorsal raphe nucleus exert a key-role in the modulation of the post-ictal antinociception.

  20. Leakage of runaway electrons from tokamaks

    SciTech Connect

    Wong, K.L.

    1982-02-01

    Runaway electron orbits are calculated in a tokamak magnetic field. It is shown that these electrons tend to drift towards a larger major radius with a velocity v Vector/sub R/ = qcE/B/sub 0/ R. This effect may be relevant to some recent experimental observations in tokamaks.

  1. Numerical tokamak turbulence project (OFES grand challenge)

    SciTech Connect

    Beer, M; Cohen, B I; Crotinger, J; Dawson, J; Decyk, V; Dimits, A M; Dorland, W D; Hammett, G W; Kerbel, G D; Leboeuf, J N; Lee, W W; Lin, Z; Nevins, W M; Reynders, J; Shumaker, D E; Smith, S; Sydora, R; Waltz, R E; Williams, T

    1999-08-27

    The primary research objective of the Numerical Tokamak Turbulence Project (NTTP) is to develop a predictive ability in modeling turbulent transport due to drift-type instabilities in the core of tokamak fusion experiments, through the use of three-dimensional kinetic and fluid simulations and the derivation of reduced models.

  2. Natural current profiles in a tokamak

    SciTech Connect

    Taylor, J.B.

    1990-08-01

    In this paper I show how one may arrive at a universal, or natural, family of Tokamak profiles using only accepted physical principles. These particular profiles are similar to ones proposed previously on the basis of ad hoc variational principles and the point of the present paper is to provide a justification for them. However in addition, the present work provides an interesting view of Tokamak fluctuations and leads to a new result -- a relationship between the inward particle pinch velocity, the diffusion coefficient and the current profile. The basic Tokamak model is described in this paper. Then an analogy is developed between Tokamak profiles and the equilibrium of a realisable dynamical system. Then the equations governing the natural Tokamak profiles are derived by applying standard statistical mechanics to this analog. The profiles themselves are calculated and some other results of the theory are described.

  3. Linear optimal control of tokamak fusion devices

    SciTech Connect

    Kessel, C.E.; Firestone, M.A.; Conn, R.W.

    1989-05-01

    The control of plasma position, shape and current in a tokamak fusion reactor is examined using linear optimal control. These advanced tokamaks are characterized by non up-down symmetric coils and structure, thick structure surrounding the plasma, eddy currents, shaped plasmas, superconducting coils, vertically unstable plasmas, and hybrid function coils providing ohmic heating, vertical field, radial field, and shaping field. Models of the electromagnetic environment in a tokamak are derived and used to construct control gains that are tested in nonlinear simulations with initial perturbations. The issues of applying linear optimal control to advanced tokamaks are addressed, including complex equilibrium control, choice of cost functional weights, the coil voltage limit, discrete control, and order reduction. Results indicate that the linear optimal control is a feasible technique for controlling advanced tokamaks where the more common classical control will be severely strained or will not work. 28 refs., 13 figs.

  4. Transport equations in tokamak plasmas

    SciTech Connect

    Callen, J. D.; Hegna, C. C.; Cole, A. J.

    2010-05-15

    Tokamak plasma transport equations are usually obtained by flux surface averaging the collisional Braginskii equations. However, tokamak plasmas are not in collisional regimes. Also, ad hoc terms are added for neoclassical effects on the parallel Ohm's law, fluctuation-induced transport, heating, current-drive and flow sources and sinks, small magnetic field nonaxisymmetries, magnetic field transients, etc. A set of self-consistent second order in gyroradius fluid-moment-based transport equations for nearly axisymmetric tokamak plasmas has been developed using a kinetic-based approach. The derivation uses neoclassical-based parallel viscous force closures, and includes all the effects noted above. Plasma processes on successive time scales and constraints they impose are considered sequentially: compressional Alfven waves (Grad-Shafranov equilibrium, ion radial force balance), sound waves (pressure constant along field lines, incompressible flows within a flux surface), and collisions (electrons, parallel Ohm's law; ions, damping of poloidal flow). Radial particle fluxes are driven by the many second order in gyroradius toroidal angular torques on a plasma species: seven ambipolar collision-based ones (classical, neoclassical, etc.) and eight nonambipolar ones (fluctuation-induced, polarization flows from toroidal rotation transients, etc.). The plasma toroidal rotation equation results from setting to zero the net radial current induced by the nonambipolar fluxes. The radial particle flux consists of the collision-based intrinsically ambipolar fluxes plus the nonambipolar fluxes evaluated at the ambipolarity-enforcing toroidal plasma rotation (radial electric field). The energy transport equations do not involve an ambipolar constraint and hence are more directly obtained. The 'mean field' effects of microturbulence on the parallel Ohm's law, poloidal ion flow, particle fluxes, and toroidal momentum and energy transport are all included self-consistently. The

  5. The Microwave Tokamak Experiment (MTX)

    SciTech Connect

    Thomassen, K.I.; Cohen, B.I.; Hooper, E.B.; Lang, D.D.; Nevins, W.M.

    1987-10-02

    A new experimental facility is being assembled at the Lawrence Livermore National Laboratory (LLNL) for studying microwave propagation and absorption in high density plasmas. A unique feature of the facility is the free electron laser (FEL) used to generate high peak power microwaves at 250 GHz, at a repetition rate so as to produce up to 2 MW of average power for up to 30 s. Called the Microwave Tokamak Experiment (MTX), the facility will be used for studies of plasma heating, current drive, and confinement.

  6. Alpha particle confinement in tokamaks

    SciTech Connect

    White, R.B.; Mynick, H.E.

    1988-11-01

    An assessment of diffusive tokamak transport mechanisms of concern for alpha particles indicates that the ''stochastic regime'' is the only one which appears to pose a real danger for adequate alpha confinement. This fact, in conjunction with the threshold character of that mechanism, allows one to decide whether an alpha born at a given location will be lost or confined, according to a very simple criterion. Implementing this criterion numerically results in a new code for the assessment of alpha confinement, which is orders of magnitude faster than earlier codes used for this purpose. 13 refs., 3 figs., 1 tab.

  7. Breakdown in the pretext tokamak

    SciTech Connect

    Benesch, J.F.

    1981-06-01

    Data are presented on the application of ion cyclotron resonance RF power to preionization in tokamaks. We applied 0.3-3 kW at 12 MHz to hydrogen and obtained a visible discharge, but found no scaling of breakdown voltage with any parameter we were able to vary. A possible explanation for this, which implies that higher RF power would have been much more effective, is discussed. Finally, we present our investigation of the dV/dt dependence of breakdown voltage in PRETEXT, a phenomenon also seen in JFT-2. The breakdown is discussed in terms of the physics of Townsend discharges.

  8. Noniterative reconstruction of tokamak equilibria

    NASA Astrophysics Data System (ADS)

    Rodrigues, Paulo; Bizarro, João P. S.

    2009-02-01

    Unlike iterative approaches, noniterative equilibria reconstruction schemes are designed to keep two measured internal profiles fixed along a given chord while solving a sequence of linear differential equations, providing a unique and asymptotic solution to the Grad-Shafranov (GS) equation directly in laboratory coordinates. A noniterative algorithm is extended to handle plasma configurations that are not symmetric with respect to the tokamak midplane and then used to compute an equilibrium solution from an actual experimental data set. A number of issues concerning how available experimental data can be handled and provided as input to the GS solver in practical situations are also discussed.

  9. Tokamak Physics Experiment divertor design

    SciTech Connect

    Anderson, P.M.

    1995-12-31

    The Tokamak Physics Experiment (TPX) tokamak requires a symmetric up/down double-null divertor capable of operation with steady-state heat flux as high as 7.5 MW/m{sup 2}. The divertor is designed to operate in the radiative mode and employs a deep slot configuration with gas puffing lines to enhance radiative divertor operation. Pumping is provided by cryopumps that pump through eight vertical ports in the floor and ceiling of the vessel. The plasma facing surface is made of carbon-carbon composite blocks (macroblocks) bonded to multiple parallel copper tubes oriented vertically. Water flowing at 6 m/s is used, with the critical heat flux (CHF) margin improved by the use of enhanced heat transfer surfaces. In order to extend the operating period where hands on maintenance is allowed and to also reduce dismantling and disposal costs, the TPX design emphasizes the use of low activation materials. The primary materials used in the divertor are titanium, copper, and carbon-carbon composite. The low activation material selection and the planned physics operation will allow personnel access into the vacuum vessel for the first 2 years of operation. The remote handling system requires that all plasma facing components (PFCs) are configured as modular components of restricted dimensions with special provisions for lifting, alignment, mounting, attachment, and connection of cooling lines, and instrumentation and diagnostics services.

  10. Predictive Modeling of Tokamak Configurations*

    NASA Astrophysics Data System (ADS)

    Casper, T. A.; Lodestro, L. L.; Pearlstein, L. D.; Bulmer, R. H.; Jong, R. A.; Kaiser, T. B.; Moller, J. M.

    2001-10-01

    The Corsica code provides comprehensive toroidal plasma simulation and design capabilities with current applications [1] to tokamak, reversed field pinch (RFP) and spheromak configurations. It calculates fixed and free boundary equilibria coupled to Ohm's law, sources, transport models and MHD stability modules. We are exploring operations scenarios for both the DIII-D and KSTAR tokamaks. We will present simulations of the effects of electron cyclotron heating (ECH) and current drive (ECCD) relevant to the Quiescent Double Barrier (QDB) regime on DIII-D exploring long pulse operation issues. KSTAR simulations using ECH/ECCD in negative central shear configurations explore evolution to steady state while shape evolution studies during current ramp up using a hyper-resistivity model investigate startup scenarios and limitations. Studies of high bootstrap fraction operation stimulated by recent ECH/ECCD experiments on DIIID will also be presented. [1] Pearlstein, L.D., et al, Predictive Modeling of Axisymmetric Toroidal Configurations, 28th EPS Conference on Controlled Fusion and Plasma Physics, Madeira, Portugal, June 18-22, 2001. * Work performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under contract No. W-7405-Eng-48.

  11. Theoretical Transport Model for Tokamaks

    NASA Astrophysics Data System (ADS)

    Ghanem, Elsayed Mohammad

    In the present thesis work a theoretical transport model is suggested to study the anomalous transport of plasma particles and energy across the axisymmetric equilibrium toroidal magnetic flux surfaces in tokamaks. The model suggests a linear combination of two transport mechanisms; drift waves, which dominate the transport in the core region, and resistive ballooning modes, which dominate the transport in the edge region. The resulting unified model has been used in a predictive transport code to simulate the plasma transport in different tokamak experiments operating in both the ohmic heating phase and the low confinement mode (L-mode). For ohmic plasma, the model was used to study the saturation of energy confinement time at high plasma density. The effect of the resistive ballooning mode as a possible cause of the saturation phenomena has been investigated together with the effect of the ion temperature gradient mode. For the low confinement mode plasmas, the study has emphasized on using the model to obtain a scaling law for the energy confinement time with the various plasma parameters compared to the scaling laws that are derived based on fitting the experimental data.

  12. Superconducting magnet system for the TPX Tokamak

    NASA Astrophysics Data System (ADS)

    Hassenzahl, W. V.; Chaplin, M. R.; Heim, J. R.; Lang, D. D.; O'Connor, T. G.; Slack, D. S.; Wong, R. L.; Zbasnik, J. P.; Brown, T. G.; Citrolo, J. C.

    1994-07-01

    The Tokamak Physics Experiment (TPX) will be the first Tokamak using superconducting magnets for both the poloidal and toroidal field. It is designed for advanced Tokamak physics experiments in steady-state and long-pulse operation. The TPX superconducting magnets use an advanced cable-in-conduit conductor (CICC) design similar to that developed in support of the International Thermonuclear Experimental Reactor (ITER). The toroidal field magnets provide 4.0 T at 2.25 m with a stored energy of 1.05 GJ. The poloidal field magnets provide 18.0 V-s to ohmically start and control long burns of a 2.0 MA plasma.

  13. Superconducting magnet system for the TPX Tokamak

    SciTech Connect

    Hassenzahl, W.V.; Chaplin, M.R.; Heim, J.R.

    1993-09-15

    The Tokamak Physics Experiment (TPX) will be the first Tokamak using superconducting magnets for both the poloidal and toroidal field. It is designed for advanced Tokamak physics experiments in steady-state and long-pulse operation. The TPX superconducting magnets use an advanced cable-in-conduit conductor (CICC) design similar to that developed in support of the International Thermonuclear Experimental Reactor (ITER). The toroidal field magnets provide 4.0 T at 2.25 m with a stored energy of 1.05 GJ. The poloidal field magnets provide 18.0 V-s to ohmically start and control long burns of a 2.0 MA plasma.

  14. Superconducting magnet system for the TPX Tokamak

    SciTech Connect

    Hassenzahl, W.V.; Chaplin, M.R.; Heim, J.R.

    1994-07-01

    The Tokamak Physics Experiment (TPX) will be the first Tokamak using superconducting magnets for both the poloidal and toroidal field. It is designed for advanced Tokamak physics experiments in steady-state and long-pulse operation. The TPC superconducting magnets use an advanced cable-in-conduit conductor (CICC) design similar to that developed in support of the International Thermonuclear Experimental Reactor (ITER). The toroidal field magnets provide 4.0 T at 2.25 m with a stored energy of 1.05 GJ. The poloidal field magnets provide 18.0 V-s to ohmically start and control long burns of a 2.0 MA plasma.

  15. Prepuberal Stimulation of 5-HT7-R by LP-211 in a Rat Model of Hyper-Activity and Attention-Deficit: Permanent Effects on Attention, Brain Amino Acids and Synaptic Markers in the Fronto-Striatal Interface

    PubMed Central

    Treno, Concetta; Gironi Carnevale, Ugo A.; Arra, Claudio; Nieddu, Maria; Pagano, Cristina; Illiano, Placido; Barbato, Fabiana; Carboni, Ezio; Laviola, Giovanni; Lacivita, Enza; Leopoldo, Marcello; Adriani, Walter; Sadile, Adolfo G.

    2014-01-01

    The cross-talk at the prefronto-striatal interface involves excitatory amino acids, different receptors, transducers and modulators. We investigated long-term effects of a prepuberal, subchronic 5-HT7-R agonist (LP-211) on adult behaviour, amino acids and synaptic markers in a model for Attention-Deficit/Hyperactivity Disorder (ADHD). Naples High Excitability rats (NHE) and their Random Bred controls (NRB) were daily treated with LP-211 in the 5th and 6th postnatal week. One month after treatment, these rats were tested for indices of activity, non selective (NSA), selective spatial attention (SSA) and emotionality. The quantity of L-Glutamate (L-Glu), L-Aspartate (L-Asp) and L-Leucine (L-Leu), dopamine transporter (DAT), NMDAR1 subunit and CAMKIIα, were assessed in prefrontal cortex (PFC), dorsal (DS) and ventral striatum (VS), for their role in synaptic transmission, neural plasticity and information processing. Prepuberal LP-211 (at lower dose) reduced horizontal activity and (at higher dose) increased SSA, only for NHE but not in NRB rats. Prepuberal LP-211 increased, in NHE rats, L-Glu in the PFC and L-Asp in the VS (at 0.250 mg/kg dose), whereas (at 0.125 mg/kg dose) it decreased L-Glu and L-Asp in the DS. The L-Glu was decreased, at 0.125 mg/kg, only in the VS of NRB rats. The DAT levels were decreased with the 0.125 mg/kg dose (in the PFC), and increased with the 0.250 mg/kg dose (in the VS), significantly for NHE rats. The basal NMDAR1 level was higher in the PFC of NHE than NRB rats; LP-211 treatment (at 0.125 mg/kg dose) decreased NMDAR1 in the VS of NRB rats. This study represents a starting point about the impact of developmental 5-HT7-R activation on neuro-physiology of attentive processes, executive functions and their neural substrates. PMID:24709857

  16. Prepuberal stimulation of 5-HT7-R by LP-211 in a rat model of hyper-activity and attention-deficit: permanent effects on attention, brain amino acids and synaptic markers in the fronto-striatal interface.

    PubMed

    Ruocco, Lucia A; Treno, Concetta; Gironi Carnevale, Ugo A; Arra, Claudio; Boatto, Gianpiero; Nieddu, Maria; Pagano, Cristina; Illiano, Placido; Barbato, Fabiana; Tino, Angela; Carboni, Ezio; Laviola, Giovanni; Lacivita, Enza; Leopoldo, Marcello; Adriani, Walter; Sadile, Adolfo G

    2014-01-01

    The cross-talk at the prefronto-striatal interface involves excitatory amino acids, different receptors, transducers and modulators. We investigated long-term effects of a prepuberal, subchronic 5-HT7-R agonist (LP-211) on adult behaviour, amino acids and synaptic markers in a model for Attention-Deficit/Hyperactivity Disorder (ADHD). Naples High Excitability rats (NHE) and their Random Bred controls (NRB) were daily treated with LP-211 in the 5th and 6th postnatal week. One month after treatment, these rats were tested for indices of activity, non selective (NSA), selective spatial attention (SSA) and emotionality. The quantity of L-Glutamate (L-Glu), L-Aspartate (L-Asp) and L-Leucine (L-Leu), dopamine transporter (DAT), NMDAR1 subunit and CAMKIIα, were assessed in prefrontal cortex (PFC), dorsal (DS) and ventral striatum (VS), for their role in synaptic transmission, neural plasticity and information processing. Prepuberal LP-211 (at lower dose) reduced horizontal activity and (at higher dose) increased SSA, only for NHE but not in NRB rats. Prepuberal LP-211 increased, in NHE rats, L-Glu in the PFC and L-Asp in the VS (at 0.250 mg/kg dose), whereas (at 0.125 mg/kg dose) it decreased L-Glu and L-Asp in the DS. The L-Glu was decreased, at 0.125 mg/kg, only in the VS of NRB rats. The DAT levels were decreased with the 0.125 mg/kg dose (in the PFC), and increased with the 0.250 mg/kg dose (in the VS), significantly for NHE rats. The basal NMDAR1 level was higher in the PFC of NHE than NRB rats; LP-211 treatment (at 0.125 mg/kg dose) decreased NMDAR1 in the VS of NRB rats. This study represents a starting point about the impact of developmental 5-HT7-R activation on neuro-physiology of attentive processes, executive functions and their neural substrates.

  17. OPTIMUM PLASMA STATES FOR NEXT STEP TOKAMAKS

    SciTech Connect

    LIN-LIU,YR; STAMBAUGH,RD

    2002-11-01

    OAK A271 OPTIMUM PLASMA STATES FOR NEXT STEP TOKAMAKS. The dependence of the ideal ballooning {beta} limit on aspect ratio, A, and elongation {kappa} is systematically explored for nearly 100% bootstrap current driven tokamak equilibria in a wide range of the shape parameters (A = 1.2-7.0, {kappa} = 1.5-6.0 with triangularity {delta} = 0.5). The critical {beta}{sub N} is shown to be optimal at {kappa} = 3.0-4.0 for all A studied and increases as A decreases with a dependence close to A{sup -0.5}. The results obtained can be used as a theoretical basis for the choice of optimum aspect ratio and elongation of next step burning plasma tokamaks or tokamak reactors.

  18. Control of Dust Inventory in Tokamaks

    SciTech Connect

    Rosanvallon, S.; Grisolia, C.; Andrew, P.; Ciattaglia, S.; Pitcher, C. S.; Taylor, N.; Furlan, J.

    2008-09-07

    Particles with sizes ranging from 100 nm to 100 {mu}m are produced in tokamaks by the interaction of the plasma with the first wall materials and divertor. Dust has not yet been of a major concern in existing tokamaks mainly because their quantities are small and these devices are not nuclear facilities. However, in ITER and in future reactors, they could represent operational and potential safety issues. The aim of this paper is thus to describe the dust creation processes in the tokamak environment. The diagnostics and removal techniques that are needed to be implemented to measure and minimise the dust inventory are also presented. The integration of these techniques into a tokamak environment is also discussed.

  19. Active tokamak limiters; symmetrizing the edge plasma

    SciTech Connect

    Motley, R.W.

    1981-02-01

    The surface layers of tokamak plasmas are strongly unstable to low frequency oscillations. The limiter, by imposing a non-axisymmetric state in the plasma scrape-off layer, may be the source of the free energy driving the instabilities. An active, two-faced sandwich limiter is proposed to symmetrize the scrape-off layer, thereby minimizing the mismatch between the inner and outer tokamak states.

  20. D-D tokamak reactor studies

    SciTech Connect

    Evans, K.E. Jr.; Baker, C.C.; Brooks, J.N.; Ehst, D.A.; Finn, P.A.; Jung, J.; Mattas, R.F.; Misra, B.; Smith, D.L.; Stevens, H.C.

    1980-11-01

    A tokamak D-D reactor design, utilizing the advantages of a deuterium-fueled reactor but with parameters not unnecessarily extended from existing D-T designs, is presented. Studies leading to the choice of a design and initial studies of the design are described. The studies are in the areas of plasma engineering, first-wall/blanket/shield design, magnet design, and tritium/fuel/vacuum requirements. Conclusions concerning D-D tokamak reactors are stated.

  1. Burn Control Mechanisms in Tokamaks

    NASA Astrophysics Data System (ADS)

    Hill, M. A.; Stacey, W. M.

    2015-11-01

    Burn control and passive safety in accident scenarios will be an important design consideration in future tokamak reactors, in particular fusion-fission hybrid reactors, e.g. the Subcritical Advanced Burner Reactor. We are developing a burning plasma dynamics code to explore various aspects of burn control, with the intent to identify feedback mechanisms that would prevent power excursions. This code solves the coupled set of global density and temperature equations, using scaling relations from experimental fits. Predictions of densities and temperatures have been benchmarked against DIII-D data. We are examining several potential feedback mechanisms to limit power excursions: i) ion-orbit loss, ii) thermal instability density limits, iii) MHD instability limits, iv) the degradation of alpha-particle confinement, v) modifications to the radial current profile, vi) ``divertor choking'' and vii) Type 1 ELMs. Work supported by the US DOE under DE-FG02-00ER54538, DE-FC02-04ER54698.

  2. Do spherical tokamaks have a thermonuclear future?

    NASA Astrophysics Data System (ADS)

    Mirnov, S. V.

    2012-12-01

    This work has been initiated by the publication of a review by B.V.Kuteev et al., "Intense Fusion Neutron Sources" [Plasma Physics Reports 36, 281 (2010)]. It is stated that the key thesis of the above review that a spherical tokamak can be recommended for research neutron sources and for demonstration hybrid systems as an alternative to expensive "classical" tokamaks of the JET and ITER type is inconsistent. The analysis of the experimental material obtained during the last 10 years in the course of studies on the existing spherical tokamaks shows that the TIN-ST fusion neutron source spherical tokamak proposed by the authors of the review and intended, according to the authors' opinion, to replace "monsters" in view of its table-top dimensions (2 m3) and laboratory-level energetics cannot be transformed into any noticeable stationary megawatt-power neutron source competing with the existing classical tokamaks (in particular, with JET with its quasi-steady DT fusion power at a level of 5 MW). Namely, the maximum plasma current in the proposed tokamak will be not 3 MA, as the authors suppose erroneously, but, according to the present-day practice of spherical tokamaks, within 0.6-0.7 MA, which will lead to a reduction on the neutron flux by two to three orders of magnitude from the expected 5 MW. The possibility of the maintenance of the stationary process itself even in such a "weakened" spherical tokamak is very doubtful. The experience of the largest existing devices of this type (such as NSTX and MAST) has shown that they are incapable of operating even in a quasi-steady operating mode, because the discharge in them is spontaneously interrupted about 1 s after the beginning of the current pulse, although its expected duration is of up to 5 s. The nature of this phenomenon is the subject of further study of the physics of spherical tokamaks. This work deals with a critical analysis of the available experimental data concerning such tokamaks and a discussion of

  3. Mission and physics design of the Tokamak Physics Experiment

    SciTech Connect

    Neilson, G.H.; Batchelor, D.B.; Mioduszewski, P.K.; Strickler, D.J.; Bonoli, P.T.; Porkolab, M.; Goldston, R.J.; Jardin, S.C.; Bialek, J.M.; Kessel, C.E.

    1994-11-01

    Improvements in the confinement, stability limits, current-drive efficiency and divertor performance, combined with steady-state operation, can lead to a more economical tokamak fusion reactor than one based on the present physics data base. The Tokamak Physics Experiment (TPX) is planned to extend the recent advances in these areas, achieved in pulsed tokamaks, to the steady-state regime. In so doing, it will develop a data base needed for the design of an economically attractive tokamak reactor.

  4. Plasma Physics Regimes in Tokamaks with Li Walls

    SciTech Connect

    L.E. Zakharo; N.N. Gorelenkov; R.B. White; S.I. Krasheninnikov; G.V. Pereverzev

    2003-08-21

    Low recycling regimes with a plasma limited by a lithium wall surface suggest enhanced stability and energy confinement, both necessary for tokamak reactors. These regimes could make ignition feasible in compact tokamaks. Ignited Spherical Tokamaks (IST), self-sufficient in the bootstrap current, are introduced as a necessary step for development of the physics and technology of power reactors.

  5. Bifurcated helical core equilibrium states in tokamaks

    NASA Astrophysics Data System (ADS)

    Cooper, W. A.; Chapman, I. T.; Schmitz, O.; Turnbull, A. D.; Tobias, B. J.; Lazarus, E. A.; Turco, F.; Lanctot, M. J.; Evans, T. E.; Graves, J. P.; Brunetti, D.; Pfefferlé, D.; Reimerdes, H.; Sauter, O.; Halpern, F. D.; Tran, T. M.; Coda, S.; Duval, B. P.; Labit, B.; Pochelon, A.; Turnyanskiy, M. R.; Lao, L.; Luce, T. C.; Buttery, R.; Ferron, J. R.; Hollmann, E. M.; Petty, C. C.; van Zeeland, M.; Fenstermacher, M. E.; Hanson, J. M.; Lütjens, H.

    2013-07-01

    Tokamaks with weak to moderate reversed central shear in which the minimum inverse rotational transform (safety factor) qmin is in the neighbourhood of unity can trigger bifurcated magnetohydrodynamic equilibrium states, one of which is similar to a saturated ideal internal kink mode. Peaked prescribed pressure profiles reproduce the ‘snake’ structures observed in many tokamaks which has led to a novel explanation of the snake as a bifurcated equilibrium state. Snake equilibrium structures are computed in simulations of the tokamak à configuration variable (TCV), DIII-D and mega amp spherical torus (MAST) tokamaks. The internal helical deformations only weakly modulate the plasma-vacuum interface which is more sensitive to ripple and resonant magnetic perturbations. On the other hand, the external perturbations do not alter the helical core deformation in a significant manner. The confinement of fast particles in MAST simulations deteriorate with the amplitude of the helical core distortion. These three-dimensional bifurcated solutions constitute a paradigm shift that motivates the applications of tools developed for stellarator research in tokamak physics investigations.

  6. Tokamak x ray diagnostic instrumentation

    SciTech Connect

    Hill, K.W.; Beiersdorfer, P.; Bitter, M.; Fredrickson, E.; Von Goeler, S.; Hsuan, H.; Johnson, L.C.; Liew, S.L.; McGuire, K.; Pare, V.

    1987-01-01

    Three classes of x-ray diagnostic instruments enable measurement of a variety of tokamak physics parameters from different features of the x-ray emission spectrum. (1) The soft x-ray (1 to 50 keV) pulse-height-analysis (PHA) diagnostic measures impurity concentrations from characteristic line intensities and the continuum enhancement, and measures the electron temperature from the continuum slope. (2) The Bragg x-ray crystal spectrometer (XCS) measures the ion temperature and neutral-beam-induced toroidal rotation velocity from the Doppler broadening and wavelength shift, respectively, of spectral lines of medium-Z impurity ions. Impurity charge state distributions, precise wavelengths, and inner-shell excitation and recombination rates can also be studied. X rays are diffracted and focused by a bent crystal onto a position-sensitive detector. The spectral resolving power E/..delta..E is greater than 10/sup 4/ and time resolution is 10 ms. (3) The x-ray imaging system (XIS) measures the spatial structure of rapid fluctuations (0.1 to 100 kHZ) providing information on MHD phenomena, impurity transport rates, toroidal rotation velocity, plasma position, and the electron temperature profile. It uses an array of silicon surface-barrier diodes which view different chords of the plasma through a common slot aperture and operate in current (as opposed to counting) mode. The effectiveness of shields to protect detectors from fusion-neutron radiation effects has been studied both theoretically and experimentally.

  7. Intrinsic rotation in tokamaks: theory

    NASA Astrophysics Data System (ADS)

    Parra, Felix I.; Barnes, Michael

    2015-04-01

    Self-consistent equations for intrinsic rotation in tokamaks with small poloidal magnetic field Bp compared to the total magnetic field B are derived. The model gives the momentum redistribution due to turbulence, collisional transport and energy injection. Intrinsic rotation is determined by the balance between the momentum redistribution and the turbulent diffusion and convection. Two different turbulence regimes are considered: turbulence with characteristic perpendicular lengths of the order of the ion gyroradius, ρi, and turbulence with characteristic lengths of the order of the poloidal gyroradius, (B/Bp)ρi. Intrinsic rotation driven by gyroradius scale turbulence is mainly due to the effect of neoclassical corrections and of finite orbit widths on turbulent momentum transport, whereas for the intrinsic rotation driven by poloidal gyroradius scale turbulence, the slow variation of turbulence characteristics in the radial and poloidal directions and the turbulent particle acceleration can be become as important as the neoclassical and finite orbit width effects. The magnetic drift is shown to be indispensable for the intrinsic rotation driven by the slow variation of turbulence characteristics and the turbulent particle acceleration. The equations are written in a form conducive to implementation in a flux tube code, and the effect of the radial variation of the turbulence is included in a novel way that does not require a global gyrokinetic formalism.

  8. Microtearing modes in tokamak discharges

    NASA Astrophysics Data System (ADS)

    Rafiq, T.; Weiland, J.; Kritz, A. H.; Luo, L.; Pankin, A. Y.

    2016-06-01

    Microtearing modes (MTMs) have been identified as a source of significant electron thermal transport in tokamak discharges. In order to describe the evolution of these discharges, it is necessary to improve the prediction of electron thermal transport. This can be accomplished by utilizing a model for transport driven by MTMs in whole device predictive modeling codes. The objective of this paper is to develop the dispersion relation that governs the MTM driven transport. A unified fluid/kinetic approach is used in the development of a nonlinear dispersion relation for MTMs. The derivation includes the effects of electrostatic and magnetic fluctuations, arbitrary electron-ion collisionality, electron temperature and density gradients, magnetic curvature, and the effects associated with the parallel propagation vector. An iterative nonlinear approach is used to calculate the distribution function employed in obtaining the nonlinear parallel current and the nonlinear dispersion relation. The third order nonlinear effects in magnetic fluctuations are included, and the influence of third order effects on a multi-wave system is considered. An envelope equation for the nonlinear microtearing modes in the collision dominant limit is introduced in order to obtain the saturation level. In the limit that the mode amplitude does not vary along the field line, slab geometry, and strong collisionality, the fluid dispersion relation for nonlinear microtearing modes is found to agree with the kinetic dispersion relation.

  9. Microtearing modes in tokamak discharges

    SciTech Connect

    Rafiq, T.; Kritz, A. H.; Weiland, J.; Luo, L.; Pankin, A. Y.

    2016-06-15

    Microtearing modes (MTMs) have been identified as a source of significant electron thermal transport in tokamak discharges. In order to describe the evolution of these discharges, it is necessary to improve the prediction of electron thermal transport. This can be accomplished by utilizing a model for transport driven by MTMs in whole device predictive modeling codes. The objective of this paper is to develop the dispersion relation that governs the MTM driven transport. A unified fluid/kinetic approach is used in the development of a nonlinear dispersion relation for MTMs. The derivation includes the effects of electrostatic and magnetic fluctuations, arbitrary electron-ion collisionality, electron temperature and density gradients, magnetic curvature, and the effects associated with the parallel propagation vector. An iterative nonlinear approach is used to calculate the distribution function employed in obtaining the nonlinear parallel current and the nonlinear dispersion relation. The third order nonlinear effects in magnetic fluctuations are included, and the influence of third order effects on a multi-wave system is considered. An envelope equation for the nonlinear microtearing modes in the collision dominant limit is introduced in order to obtain the saturation level. In the limit that the mode amplitude does not vary along the field line, slab geometry, and strong collisionality, the fluid dispersion relation for nonlinear microtearing modes is found to agree with the kinetic dispersion relation.

  10. Toroidal Flow in Tokamak Plasmas

    NASA Astrophysics Data System (ADS)

    Callen, J. D.; Cole, A. J.; Hegna, C. C.

    2007-11-01

    Many effects influence toroidal flow evolution in tokamak plasmas. Momentum sources and radial diffusion due to axisymmetric neoclassical, paleoclassical and anomalous transport are usually considered. In addition, the toroidal flow can be affected by field errors. Small, non-axisymmetric field errors arise from coil irregularities, active control coils and collective plasma magnetic distortions (e.g., NTMs, RWMs). Resonant field errors cause localized electromagnetic torques near rational surfaces in the plasma, which can lock the plasma to the wall leading to magnetic islands and reduced confinement or disruptions. Their penetration into the plasma is limited by flow-shielding effects; but they can be amplified by the plasma response at high beta. Non-resonant field errors cause magnetic pumping and radial banana drifts, and lead to toroidal flow damping over the entire plasma. Many of these processes can also produce momentum pinch and intrinsic flow effects. This poster will seek to present a coherent picture of all these effects and suggest ways they could be tested and distinguished experimentally.

  11. Dust in tokamaks: An overview of the physical model of the dust in tokamaks code

    NASA Astrophysics Data System (ADS)

    Bacharis, Minas; Coppins, Michael; Allen, John E.

    2010-04-01

    The dynamical behavior of dust produced in tokamaks is an important issue for fusion. In this work, the current status of the dust in tokamaks (DTOKS) [J. D. Martin et al., Europhys Lett. 83, 65001 (2008)] dust transport code will be presented. A detailed description of the various elements of its underlying physical model will be given together with representative simulation results for the mega amp spherical tokamak (MAST) [A. Sykes et al., Nucl. Fusion 41, 1423 (2001)]. Furthermore, a brief description of the various components of the dust transport (DUSTT) [R. D. Smirnov et al., Plasma Phys. Controlled Fusion 49, 347 (2007)] code will also be presented in comparison with DTOKS.

  12. Activation analysis of the compact ignition tokamak

    SciTech Connect

    Selcow, E.C.

    1986-01-01

    The US fusion program has completed the conceptual design of a compact tokamak device that achieves ignition. The high neutron wall loadings associated with this compact deuterium-tritium-burning device indicate that radiation-related issues may be significant considerations in the overall system design. Sufficient shielding will be requied for the radiation protection of both reactor components and occupational personnel. A close-in igloo shield has been designed around the periphery of the tokamak structure to permit personnel access into the test cell after shutdown and limit the total activation of the test cell components. This paper describes the conceptual design of the igloo shield system and discusses the major neutronic concerns related to the design of the Compact Ignition Tokamak.

  13. Helicity content and tokamak applications of helicity

    SciTech Connect

    Boozer, A.H.

    1986-05-01

    Magnetic helicity is approximately conserved by the turbulence associated with resistive instabilities of plasmas. To generalize the application of the concept of helicity, the helicity content of an arbitrary bounded region of space will be defined. The definition has the virtues that both the helicity content and its time derivative have simple expressions in terms of the poloidal and toroidal magnetic fluxes, the average toroidal loop voltage and the electric potential on the bounding surface, and the volume integral of E-B. The application of the helicity concept to tokamak plasmas is illustrated by a discussion of so-called MHD current drive, an example of a stable tokamak q profile with q less than one in the center, and a discussion of the possibility of a natural steady-state tokamak due to the bootstrap current coupling to tearing instabilities.

  14. Physics of Tokamak Plasma Start-up

    NASA Astrophysics Data System (ADS)

    Mueller, Dennis

    2012-10-01

    This tutorial describes and reviews the state-of-art in tokamak plasma start-up and its importance to next step devices such as ITER, a Fusion Nuclear Science Facility and a Tokamak/ST demo. Tokamak plasma start-up includes breakdown of the initial gas, ramp-up of the plasma current to its final value and the control of plasma parameters during those phases. Tokamaks rely on an inductive component, typically a central solenoid, which has enabled attainment of high performance levels that has enabled the construction of the ITER device. Optimizing the inductive start-up phase continues to be an area of active research, especially in regards to achieving ITER scenarios. A new generation of superconducting tokamaks, EAST and KSTAR, experiments on DIII-D and operation with JET's ITER-like wall are contributing towards this effort. Inductive start-up relies on transformer action to generate a toroidal loop voltage and successful start-up is determined by gas breakdown, avalanche physics and plasma-wall interaction. The goal of achieving steady-sate tokamak operation has motivated interest in other methods for start-up that do not rely on the central solenoid. These include Coaxial Helicity Injection, outer poloidal field coil start-up, and point source helicity injection, which have achieved 200, 150 and 100 kA respectively of toroidal current on closed flux surfaces. Other methods including merging reconnection startup and Electron Bernstein Wave (EBW) plasma start-up are being studied on various devices. EBW start-up generates a directed electron channel due to wave particle interaction physics while the other methods mentioned rely on magnetic helicity injection and magnetic reconnection which are being modeled and understood using NIMROD code simulations.

  15. Current drive by spheromak injection into a tokamak

    NASA Astrophysics Data System (ADS)

    Brown, M. R.; Bellan, P. M.

    1990-04-01

    We report the first observation of current drive by injection of a spheromak plasma into a tokamak (Caltech ENCORE small reasearch tokamak) due to the process of helicity injection. After an abrupt 30% increase, the tokamak current decays by a factor of 3 due to plasma cooling caused by the merging of the relatively cold spheromak with the tokamak. The tokamak density profile peaks sharply due to the injected spheromak plasma (n¯3 increases by a factor of 6) then becomes hollow, suggestive of an interchange instability.

  16. Electron cyclotron emission diagnostics on KSTAR tokamak

    SciTech Connect

    Jeong, S. H.; Lee, K. D.; Kwon, M.; Kogi, Y.; Kawahata, K.; Nagayama, Y.; Mase, A.

    2010-10-15

    A new electron cyclotron emission (ECE) diagnostics system was installed for the Second Korea Superconducting Tokamak Advanced Research (KSTAR) campaign. The new ECE system consists of an ECE collecting optics system, an overmode circular corrugated waveguide system, and 48 channel heterodyne radiometer with the frequency range of 110-162 GHz. During the 2 T operation of the KSTAR tokamak, the electron temperatures as well as its radial profiles at the high field side were measured and sawtooth phenomena were also observed. We also discuss the effect of a window on in situ calibration.

  17. Overview of the National Centralized Tokamak programme

    NASA Astrophysics Data System (ADS)

    Kikuchi, M.; Tamai, H.; Matsukawa, M.; Fujita, T.; Takase, Y.; Sakurai, S.; Kizu, K.; Tsuchiya, K.; Kurita, G.; Morioka, A.; Hayashi, N.; Miura, Y.; Itoh, S.; Bialek, J.; Navratil, G.; Ikeda, Y.; Fujii, T.; Kurihara, K.; Kubo, H.; Kamada, Y.; Miya, N.; Suzuki, T.; Hamamatsu, K.; Kawashima, H.; Kudo, Y.; Masaki, K.; Takahashi, H.; Takechi, M.; Akiba, M.; Okuno, K.; Ishida, S.; Ichimura, M.; Imai, T.; Hashizume; Miura, Y. M.; Horiike, H.; Kimura, A.; Tsutsui, H.; Matsuoka, M.; Uesugi, Y.; Sagara, A.; Nishimura, A.; Shimizu, A.; Sakamoto, M.; Nakamura, K.; Sato, K.; Okano, K.; Ida, K.; Shimada, H. R.; Kishimoto, Y.; Azechi, H.; Tanaka, S.; Yatsu, K.; Yoshida, N.; Inutake, M.; Fujiwara, M.; Inoue, N.; Hosogane, N.; Kuriyama, M.; Ninomiya, H.

    2006-03-01

    An overview is given of the National Centralized Tokamak (NCT) programme as a research programme for advanced tokamak research to succeed JT-60U. The mission of NCT is to establish high beta steady-state operation for DEMO and to contribute to ITER. The machine flexibility is pursued in aspect ratio and shape controllability for the demonstration of the high-β steady-state, feedback control of resistive wall modes, wide current and pressure profile control capability and also very long pulse steady-state operation. Existing JT-60 infrastructure such as the heating and current drive system, power supplies and cooling systems will be best utilized for this modification.

  18. Overview of spherical tokamak research in Japan

    NASA Astrophysics Data System (ADS)

    Takase, Y.; Ejiri, A.; Fujita, T.; Fukumoto, N.; Fukuyama, A.; Hanada, K.; Idei, H.; Nagata, M.; Ono, Y.; Tanaka, H.; Uchida, M.; Horiuchi, R.; Kamada, Y.; Kasahara, H.; Masuzaki, S.; Nagayama, Y.; Oishi, T.; Saito, K.; Takeiri, Y.; Tsuji-Iio, S.

    2017-10-01

    Nationally coordinated research on spherical tokamak is being conducted in Japan. Recent achievements include: (i) plasma current start-up and ramp-up without the use of the central solenoid by RF waves (in electron cyclotron and lower hybrid frequency ranges), (ii) plasma current start-up by AC Ohmic operation and by coaxial helicity injection, (iii) development of an advanced fuelling technique by compact toroid injection, (iv) ultra-long-pulse operation and particle control using a high temperature metal wall, (v) access to the ultra-high-β regime by high-power reconnection heating, and (vi) improvement of spherical tokamak plasma stability by externally applied helical field.

  19. Tokamak power systems studies, FY 1985

    SciTech Connect

    Baker, C.C.; Brooks, J.N.; Ehst, D.A.; Smith, D.L.; Sze, D.K.

    1985-12-01

    The Tokamak Power System Studies (TPSS) at ANL in FY-1985 were devoted to exploring innovative design concepts which have the potential for making substantial improvements in the tokamak as a commercial power reactor. Major objectives of this work included improved reactor economics, improved environmental and safety features, and the exploration of a wide range of reactor plant outputs with emphasis on reduced plant sizes compared to STARFIRE. The activities concentrated on three areas: plasma engineering, impurity control, and blanket/first wall/shield technology. 205 refs., 125 figs., 107 tabs.

  20. Tokamak Spectroscopy for X-Ray Astronomy

    NASA Technical Reports Server (NTRS)

    Fournier, Kevin B.; Finkenthal, M.; Pacella, D.; May, M. J.; Soukhanovskii, V.; Mattioli, M.; Leigheb, M.; Rice, J. E.

    2000-01-01

    This paper presents the measured x-ray and Extreme Ultraviolet (XUV) spectra of three astrophysically abundant elements (Fe, Ca and Ne) from three different tokamak plasmas. In every case, each spectrum touches on an issue of atomic physics that is important for simulation codes to be used in the analysis of high spectral resolution data from current and future x-ray telescopes. The utility of the tokamak as a laboratory test bed for astrophysical data is demonstrated. Simple models generated with the HULLAC suite of codes demonstrate how the atomic physics issues studied can affect the interpretation of astrophysical data.

  1. Transformer Recharging with Alpha Channeling in Tokamaks

    SciTech Connect

    N.J. Fisch

    2009-12-21

    Transformer recharging with lower hybrid waves in tokamaks can give low average auxiliary power if the resistivity is kept high enough during the radio frequency (rf) recharging stage. At the same time, operation in the hot ion mode via alpha channeling increases the effective fusion reactivity. This paper will address the extent to which these two large cost saving steps are compatible. __________________________________________________

  2. Spontaneous generation of rotation in tokamak plasmas

    SciTech Connect

    Parra Diaz, Felix

    2013-12-24

    Three different aspects of intrinsic rotation have been treated. i) A new, first principles model for intrinsic rotation [F.I. Parra, M. Barnes and P.J. Catto, Nucl. Fusion 51, 113001 (2011)] has been implemented in the gyrokinetic code GS2. The results obtained with the code are consistent with several experimental observations, namely the rotation peaking observed after an L-H transition, the rotation reversal observed in Ohmic plasmas, and the change in rotation that follows Lower Hybrid wave injection. ii) The model in [F.I. Parra, M. Barnes and P.J. Catto, Nucl. Fusion 51, 113001 (2011)] has several simplifying assumptions that seem to be satisfied in most tokamaks. To check the importance of these hypotheses, first principles equations that do not rely on these simplifying assumptions have been derived, and a version of these new equations has been implemented in GS2 as well. iii) A tokamak cross-section that drives large intrinsic rotation has been proposed for future large tokamaks. In large tokamaks, intrinsic rotation is expected to be very small unless some up-down asymmetry is introduced. The research conducted under this contract indicates that tilted ellipticity is the most efficient way to drive intrinsic rotation.

  3. INTEGRATED PLASMA CONTROL FOR ADVANCED TOKAMAKS

    SciTech Connect

    HUMPHREYS,D.A; FERRON,J.R; JOHNSON,R.D; LEUER,J.A; PENAFLOR,B.G; WALKER,M.L; WELANDER,A.S; KHAYRUTDINOV,R.R; DOKOUKA,V; EDGELL,D.H; FRANSSON,C.M

    2003-10-01

    OAK-B135 Advanced tokamaks (AT) are distinguished from conventional tokamaks by their high degree of shaping, achievement of profiles optimized for high confinement and stability characteristics, and active stabilization of MHD instabilities to attain high values of normalized beta and confinement. These high performance fusion devices thus require accurate regulation of the plasma boundary, internal profiles, pumping, fueling, and heating, as well as simultaneous and well-coordinated MHD control action to stabilize such instabilities as tearing modes and resistive wall modes. Satisfying the simultaneous demands on control accuracy, reliability, and performance for all of these subsystems requires a high degree of integration in both design and operation of the plasma control system in an advanced tokamak. The present work describes the approach, benefits, and progress made in integrated plasma control with application examples drawn from the DIII-D tokamak. The approach includes construction of plasma and system response models, validation of models against operating experiments, design of integrated controllers which operate in concert with one another as well as with supervisory modules, simulation of control action against off-line and actual machine control platforms, and iteration of the design-test loop to optimize performance.

  4. Simulation of runaway electrons in tokamak

    NASA Astrophysics Data System (ADS)

    Guo, Zehua; Tang, Xianzhu; McDevitt, Chris

    2015-11-01

    Runaway electrons with relativisitc energy (>Mev) are generated in tokamaks when the acceleration by parallel electric field exceeds the drag due to Coulomb collisions with the bulk plasma. Carrying about 70% of the ITER thermal current (15MA), they can possibly cause severe damage to tokamak facing components. Here we report the development of a solver for computing the evolution of runaway electron distribution in tokamak geometries. Essential effects from Coulomb collisions, radiation losses, toroidal effects and the radial transport are included on the same footings. Numerical techniques (implicit-explicit time-stepping, KT/NT central schemes) to overcome the difficulties arising from the wide spread of time scales in runaway electron dynamics and the hyperbolic nature of the relativistic Fokker-Planck equation will be discussed. We will use the solver to study two important physics: 1) the presence of stable point in the phase space and its relation to the electric field threshold; 2) the radial transport of runaways in tokamak geometry and its effects on the distribution function. Work supported by DOE via LANL-LDRD.

  5. Tokamak startup with electron cyclotron heating

    SciTech Connect

    Holly, D J; Prager, S C; Shepard, D A; Sprott, J C

    1980-04-01

    Experiments are described in which the startup voltage in a tokamak is reduced by approx. 60% by the use of a modest amount of electron cyclotron resonance heating power for preionization. A 50% reduction in volt-second requirement and impurity reflux are also observed.

  6. Analysis of sawtooth relaxation oscillations in tokamaks

    SciTech Connect

    Yamazaki, K.; McGuire, K.; Okabayashi, M.

    1982-07-01

    Sawtooth relaxation oscillations are analyzed using the Kadomtsev's disruption model and a thermal relaxation model. The sawtooth period is found to be very sensitive to the thermal conduction loss. Qualitative agreement between these calculations and the sawtooth period observed in several tokamaks is demonstrated.

  7. Banana drift transport in tokamaks with ripple

    SciTech Connect

    Linsker, R.; Boozer, A.H.

    1982-01-01

    Ripple transport in tokamaks is discussed for the ''banana drift'' collisionality regime, which lies below the ripple plateau regime treated earlier. The physical mechanisms that dominate banana drift transport are found to differ from those considered in previous work on this regime, and consequently the resulting transport coefficients can differ by several orders of magnitude.

  8. Banana drift transport in tokamaks with ripple

    SciTech Connect

    Linsker, R.; Boozer, A.H.

    1981-04-01

    Ripple transport in tokamaks is discussed for the banana drift collisionality regime, which lies below the ripple plateau regime treated earlier. The physical mechanisms that dominate banana drift transport are found to differ from those considered in previous work on this regime, and the resulting transport coefficients can consequently differ by several orders of magnitude.

  9. Stabilization of tokamak plasma by lithium streams

    SciTech Connect

    L.E. Zakharov

    2000-08-07

    The stabilization theory of free-boundary magnetohydrodynamic instabilities in tokamaks by liquid lithium streams driven by magnetic propulsion is formulated. While the conventional, wall-locked, resistive wall mode can be well suppressed by the flow, a new, stream-locked mode determines the limits of the flow stabilization.

  10. UCLA Tokamak Program Close Out Report.

    SciTech Connect

    Taylor, Robert John

    2014-02-04

    The results of UCLA experimental fusion program are summarized. Starting with smaller devices like Microtor, Macrotor, CCT and ending the research on the large (5 m) Electric Tokamak. CCT was the most diagnosed device for H-mode like physics and the effects of rotation induced radial fields. ICRF heating was also studied but plasma heating of University Type Tokamaks did not produce useful results due to plasma edge disturbances of the antennae. The Electric Tokamak produced better confinement in the seconds range. However, it presented very good particle confinement due to an "electric particle pinch". This effect prevented us from reaching a quasi steady state. This particle accumulation effect was numerically explained by Shaing's enhanced neoclassical theory. The PI believes that ITER will have a good energy confinement time but deleteriously large particle confinement time and it will disrupt on particle pinching at nominal average densities. The US fusion research program did not study particle transport effects due to its undue focus on the physics of energy confinement time. Energy confinement time is not an issue for energy producing tokamaks. Controlling the ash flow will be very expensive.

  11. Microinstabilities in weak density gradient tokamak systems

    SciTech Connect

    Tang, W.M.; Rewoldt, G.; Chen, L.

    1986-04-01

    A prominent characteristic of auxiliary-heated tokamak discharges which exhibit improved (''H-mode type'') confinement properties is that their density profiles tend to be much flatter over most of the plasma radius. Depsite this favorable trend, it is emphasized here that, even in the limit of zero density gradient, low-frequency microinstabilities can persist due to the nonzero temperature gradient.

  12. Fusion reactor design studies. [ARIES Tokamak

    SciTech Connect

    Emmert, G.A.; Kulcinski, G.L.; Santarius, J.F.

    1990-10-12

    This report discusses the following topics on the ARIES tokamak: systems; plasma power balance; impurity control and fusion ash removal; fusion product ripple loss; energy conversion; reactor fueling; first wall design; shield design; reactor safety; and fuel cost and resources. (LSP)

  13. Elementary Processes Underlying Alpha Channeling in Tokamaks

    SciTech Connect

    NM.J. Fisch

    2012-06-15

    Alpha channeling in tokamaks is speculative, but also extraordinarily attractive. Waves that can accomplish this effect have been identified. Key aspects of the theory now enjoy experimental confirmation. This paper will review the elementary processes of wave-particle interactions in plasma that underlie the alpha channeling effect

  14. Diagnostics for neutral-beam-heated tokamaks

    SciTech Connect

    Goldston, R.J.

    1982-12-01

    Diagnostic techniques for neutral-beam-heated tokamak plasmas fall into three categories: (1) magnetic diagnostics for measurements of gross stored energy, (2) profile diagnostics for measurements of stored thermal and beam energy, impurity content and plasma rotation, and (3) fast time resolution diagnostics to study MHD fluctuations and micro-turbulence.

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

    NASA Astrophysics Data System (ADS)

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

    2009-05-01

    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 CO2 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. CO2 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.

  16. Neural net prediction of tokamak plasma disruptions

    NASA Astrophysics Data System (ADS)

    Hernandez, J. V.; Lin, Z.; Horton, W.; Vannucci, A.; McCool, S. C.

    1994-10-01

    The computation based on neural net algorithms in predicting minor and major disruptions in TEXT tokamak discharges has been performed. Future values of the fluctuating magnetic signal are predicted based on L past values of the magnetic fluctuation signal, measured by a single Mirnov coil. The time step used (= 0.04ms) corresponds to the experimental data sampling rate. Two kinds of approaches are adopted for the task, the contiguous future prediction and the multi-timescale prediction. Results are shown for comparison. Both networks are trained through the back-propagation algorithm with inertial terms. The degree of this success indicates that the magnetic fluctuations associated with tokamak disruptions may be characterized by a relatively low-dimensional dynamical system.

  17. Global migration of impurities in tokamaks

    NASA Astrophysics Data System (ADS)

    Hakola, A.; Airila, M. I.; Björkas, C.; Borodin, D.; Brezinsek, S.; Coad, J. P.; Groth, M.; Järvinen, A.; Kirschner, A.; Koivuranta, S.; Krieger, K.; Kurki-Suonio, T.; Likonen, J.; Lindholm, V.; Makkonen, T.; Mayer, M.; Miettunen, J.; Müller, H. W.; Neu, R.; Petersson, P.; Rohde, V.; Rubel, M.; Widdowson, A.; the ASDEX Upgrade Team; Contributors, JET-EFDA

    2013-12-01

    The migration of impurities in tokamaks has been studied with the help of tracer-injection (13C and 15N) experiments in JET and ASDEX Upgrade since 2001. We have identified a common pattern for the migrating particles: scrape-off layer flows drive impurities from the low-field side towards the high-field side of the vessel. Migration is also sensitive to the density and magnetic configuration of the plasma, and strong local variations in the resulting deposition patterns require 3D treatment of the migration process. Moreover, re-erosion of the deposited particles has to be taken into account to properly describe the migration process during steady-state operation of the tokamak.

  18. Filamentary probe on the COMPASS tokamak

    NASA Astrophysics Data System (ADS)

    Kovarik, K.; Duran, I.; Stockel, J.; Seidl, J.; Adamek, J.; Spolaore, M.; Vianello, N.; Hacek, P.; Hron, M.; Panek, R.

    2017-03-01

    This paper describes a new filamentary probe recently introduced on the COMPASS tokamak. It allows the measurement of electrostatic and magnetic properties of the filaments and their changes in dependence on distance from the separatrix in the region between a divertor and midplane. The probe head is mounted on a manipulator moving the probe radially on a shot-to-shot basis. This configuration is suitable for the long term statistical measurement of the plasma filaments and the measurement of their evolution during their propagation from the separatrix to the wall. The basics of the filamentary probe construction, the evolution of the plasma parameters, and first conditional averages of the plasma filaments in the scrape-off layer of the COMPASS tokamak during the L-mode regime are presented.

  19. Microtearing modes in spherical and conventional tokamaks

    NASA Astrophysics Data System (ADS)

    Moradi, S.; Pusztai, I.; Guttenfelder, W.; Fülöp, T.; Mollén, A.

    2013-06-01

    The onset and characteristics of microtearing modes (MTM) in the core of spherical (NSTX) and conventional tokamaks (ASDEX Upgrade and JET) are studied through local linear gyrokinetic simulations with GYRO (Candy and Belli 2011 General Atomics Report GA-A26818). For experimentally relevant core plasma parameters in the NSTX and ASDEX Upgrade tokamaks, in agreement with previous works, we find MTMs as the dominant linear instability. Also, for JET-like core parameters considered in our study an MTM is found as the most unstable mode. In all of these plasmas, finite collisionality is needed for MTMs to become unstable and the electron temperature gradient is found to be the fundamental drive. However, a significant difference is observed in the dependence of the linear growth rate of MTMs on electron temperature gradient. While it varies weakly and non-monotonically in JET and ASDEX Upgrade plasmas, in NSTX it increases with the electron temperature gradient.

  20. Rapidly Moving Divertor Plates In A Tokamak

    SciTech Connect

    S. Zweben

    2011-05-16

    It may be possible to replace conventional actively cooled tokamak divertor plates with a set of rapidly moving, passively cooled divertor plates on rails. These plates would absorb the plasma heat flux with their thermal inertia for ~10-30 sec, and would then be removed from the vessel for processing. When outside the tokamak, these plates could be cooled, cleaned, recoated, inspected, and then returned to the vessel in an automated loop. This scheme could provide nearoptimal divertor surfaces at all times, and avoid the need to stop machine operation for repair of damaged or eroded plates. We describe various possible divertor plate designs and access geometries, and discuss an initial design for a movable and removable divertor module for NSTX-U.

  1. Filamentary probe on the COMPASS tokamak.

    PubMed

    Kovarik, K; Duran, I; Stockel, J; Seidl, J; Adamek, J; Spolaore, M; Vianello, N; Hacek, P; Hron, M; Panek, R

    2017-03-01

    This paper describes a new filamentary probe recently introduced on the COMPASS tokamak. It allows the measurement of electrostatic and magnetic properties of the filaments and their changes in dependence on distance from the separatrix in the region between a divertor and midplane. The probe head is mounted on a manipulator moving the probe radially on a shot-to-shot basis. This configuration is suitable for the long term statistical measurement of the plasma filaments and the measurement of their evolution during their propagation from the separatrix to the wall. The basics of the filamentary probe construction, the evolution of the plasma parameters, and first conditional averages of the plasma filaments in the scrape-off layer of the COMPASS tokamak during the L-mode regime are presented.

  2. Models for impurity effects in tokamaks

    SciTech Connect

    Hogan, J.T.

    1980-03-01

    Models for impurity effects in tokamaks are described with an emphasis on the relationship between attainment of high ..beta.. and impurity problems. We briefly describe the status of attempts to employ neutral beam heating to achieve high ..beta.. in tokamaks and propose a qualitative model for the mechanism by which heavy metal impurities may be produced in the startup phase of the discharge. We then describe paradoxes in impurity diffusion theory and discuss possible resolutions in terms of the effects of large-scale islands and sawtooth oscillations. Finally, we examine the prospects for the Zakharov-Shafranov catastrophe (long time scale disintegration of FCT equilibria) in the context of present and near-term experimental capability.

  3. A low aspect ratio tokamak transmutation system

    NASA Astrophysics Data System (ADS)

    Qiu, L. J.; Wu, Y. C.; Xiao, B. J.; Xu, Q.; Huang, Q. Y.; Wu, B.; Chen, Y. X.; Xu, W. N.; Chen, Y. P.; Liu, X. P.

    2000-03-01

    A low aspect ratio tokamak transmutation system is proposed as an alternative application of fusion energy on the basis of a review of previous studies. This system includes: (1) a low aspect ratio tokamak as fusion neutron driver, (2) a radioactivity-clean nuclear power system as blanket, and (3) a novel concept of liquid metal centre conductor post as part of the toroidal field coils. In the conceptual design, a driver of 100 MW fusion power under 1 MW/m2 neutron wall loading can transmute the amount of high level waste (including minor actinides and fission products) produced by ten standard pressurized water reactors of 1 GW electrical power output. Meanwhile, the system can produce tritium on a self-sustaining basis and an output of about 2 GW of electrical energy. After 30 years of operation, the biological hazard potential level of the whole system will decrease by two orders of magnitude.

  4. Boundary Plasma Turbulence Simulations for Tokamaks

    SciTech Connect

    Xu, X; Umansky, M; Dudson, B; Snyder, P

    2008-05-15

    The boundary plasma turbulence code BOUT models tokamak boundary-plasma turbulence in a realistic divertor geometry using modified Braginskii equations for plasma vorticity, density (ni), electron and ion temperature (T{sub e}; T{sub i}) and parallel momenta. The BOUT code solves for the plasma fluid equations in a three dimensional (3D) toroidal segment (or a toroidal wedge), including the region somewhat inside the separatrix and extending into the scrape-off layer; the private flux region is also included. In this paper, a description is given of the sophisticated physical models, innovative numerical algorithms, and modern software design used to simulate edge-plasmas in magnetic fusion energy devices. The BOUT code's unique capabilities and functionality are exemplified via simulations of the impact of plasma density on tokamak edge turbulence and blob dynamics.

  5. The physics of tokamak start-up

    SciTech Connect

    Mueller, D.

    2013-05-15

    Tokamak start-up on present-day devices usually relies on inductively induced voltage from a central solenoid. In some cases, inductive startup is assisted with auxiliary power from electron cyclotron radio frequency heating. International Thermonuclear Experimental Reactor, the National Spherical Torus Experiment Upgrade and JT60, now under construction, will make use of the understanding gained from present-day devices to ensure successful start-up. Design of a spherical tokamak (ST) with DT capability for nuclear component testing would require an alternative to a central solenoid because the small central column in an ST has insufficient space to provide shielding for the insulators in the solenoid. Alternative start-up techniques such as induction using outer poloidal field coils, electron Bernstein wave start-up, coaxial helicity injection, and point source helicity injection have been used with success, but require demonstration of scaling to higher plasma current.

  6. Tritium Retention and Removal in Tokamaks

    SciTech Connect

    Skinner, Charles H.

    2009-02-19

    Management of tritium inventory remains one of the grand challenges in the development of fusion energy. Tritium is an important source term in safety assessments, it is expensive and in short supply. Tritium can be continuously retained in a tokamak by codeposition with eroded carbon or beryllium and JET and TFTR with carbon plasma facing components showed a tritium retention level that would be unacceptable in ITER or future fusion reactors. Asdex-U and Alcator C-mod have shown reduced hydrogenic retention with tungsten clad and molybdenum plasma facing components. Once the tritium inventory approaches the administrative limit, tritium must be removed to permit continued D-T plasma operations. Several candidate techniques are being considered and need to be proven at a relevant speed and efficiency in contemporary tokamaks. Projections for ITER are discussed.

  7. The Physics of Tokamak Start-up

    SciTech Connect

    D. Mueller

    2012-11-13

    Tokamak start-up on present-day devices usually relies on inductively induced voltage from a central solenoid. In some cases inductive startup is assisted with auxiliary power from electron cyclotron radio frequency heating. ITER, the National Spherical Torus eXperiment Upgrade and JT60, now under construction, will make use of the understanding gained from present-day devices to ensure successful start-up. Design of a spherical tokamak (ST) with DT capability for nuclear component testing would require an alternative to a central solenoid because the small central column in an ST has insufficient space to provide shielding for the insulators in the solenoid. Alternative start-up techniques such as induction using outer poloidal field coils, electron Bernstein wave start-up, coaxial helicity injection and point source helicity injection have been used with success, but require demonstration of scaling to higher plasma current.

  8. Magnetohydrodynamic stability of tokamak edge plasmas

    SciTech Connect

    Connor, J.W.; Hastie, R.J.; Wilson, H.R.; Miller, R.L.

    1998-07-01

    A new formalism for analyzing the magnetohydrodynamic stability of a limiter tokamak edge plasma is developed. Two radially localized, high toroidal mode number n instabilities are studied in detail: a peeling mode and an edge ballooning mode. The peeling mode, driven by edge current density and stabilized by edge pressure gradient, has features which are consistent with several properties of tokamak behavior in the high confinement {open_quotes}H{close_quotes}-mode of operation, and edge localized modes (or ELMs) in particular. The edge ballooning mode, driven by the pressure gradient, is identified; this penetrates {approximately}n{sup 1/3} rational surfaces into the plasma (rather than {approximately}n{sup 1/2}, expected from conventional ballooning mode theory). Furthermore, there exists a coupling between these two modes and this coupling provides a picture of the ELM cycle.

  9. X-ray spectroscopy on tokamaks

    SciTech Connect

    von Goeler, S.; Bitter, M.; Cohen, S.

    1982-01-01

    During the last decade, the x-ray spectroscopy of high temperature plasmas has witnessed a rapid development. Most of the impulses have come from astrophysics, in particular, from the research on solar flares. On the other hand, the attainment of well-diagnosed, high-temperature laboratory plasmas in laser-pellet implosions and in tokamaks, has precipitated a fertile exchange between theory and experiment. Agreement and very detailed understanding has been reached for a great number of spectra with the result, that x-ray spectroscopy represents today a powerful and reliable new plasma diagnostic with important applications for fusion plasmas as well as solar flares. This paper is a short review of the experimental results from tokamaks.

  10. Self-Organized Stationary States of Tokamaks

    SciTech Connect

    Jardin, S. C.; Ferraro, N.; Krebs, I.

    2015-11-01

    We demonstrate that in a 3D resistive magnetohydrodynamic simulation, for some parameters it is possible to form a stationary state in a tokamak where a saturated interchange mode in the center of the discharge drives a near helical flow pattern that acts to nonlinearly sustain the configuration by adjusting the central loop voltage through a dynamo action. This could explain the physical mechanism for maintaining stationary nonsawtoothing "hybrid" discharges, often referred to as "flux pumping."

  11. Heating the Compact Ignition Tokamak (CIT)

    SciTech Connect

    Ignat, D.W.

    1989-11-01

    The proposed CIT starts operation in the late 1990's with 20 MW of rf heating power. The tokamak and facility are to be designed to accommodate 50 MW auxiliary heating. The heating methods new being considered are ion cyclotron heating (ICH) and electron cyclotron heating (ECH). Aspects of these systems are described, and the choice of power level and type is discussed. 18 refs.

  12. Self-Organized Stationary States of Tokamaks.

    PubMed

    Jardin, S C; Ferraro, N; Krebs, I

    2015-11-20

    We demonstrate that in a 3D resistive magnetohydrodynamic simulation, for some parameters it is possible to form a stationary state in a tokamak where a saturated interchange mode in the center of the discharge drives a near helical flow pattern that acts to nonlinearly sustain the configuration by adjusting the central loop voltage through a dynamo action. This could explain the physical mechanism for maintaining stationary nonsawtoothing "hybrid" discharges, often referred to as "flux pumping."

  13. High beta plasmas in the PBX tokamak

    SciTech Connect

    Bol, K.; Buchenauer, D.; Chance, M.; Couture, P.; Fishman, H.; Fonck, R.; Gammel, G.; Grek, B.; Ida, K.; Itami, K.

    1986-04-01

    Bean-shaped configurations favorable for high ..beta.. discharges have been investigated in the Princeton Beta Experiment (PBX) tokamak. Strongly indented bean-shaped plasmas have been successfully formed, and beta values of over 5% have been obtained with 5 MW of injected neutral beam power. These high beta discharges still lie in the first stability regime for ballooning modes, and MHD stability analysis implicates the external kink as responsible for the present ..beta.. limit.

  14. Instrumentation and controls of an ignited Tokamak

    NASA Astrophysics Data System (ADS)

    Becraft, W. R.; Golzy, J.; Houlberg, W. A.; Kukielka, C. A.; Onega, R. J.; Raju, G. V. S.; Stone, R. S.

    1980-10-01

    The instrumentation and controls of an ignited plasma magnetically confined in a Tokamak configuration needs increased emphasis in the following areas: (1) physics implications for control; (2) plasma shaping/position control; and (3) control to prevent disruptive instabilities. Effort in these and other areas are reported. The appendices focus attention on some preliminary ideas about the measurement of the deuteron-triton ratio in the plasma, synchrotron radiation, and divertor control.

  15. Tokamak with liquid metal toroidal field coil

    DOEpatents

    Ohkawa, Tihiro; Schaffer, Michael J.

    1981-01-01

    Tokamak apparatus includes a pressure vessel for defining a reservoir and confining liquid therein. A toroidal liner disposed within the pressure vessel defines a toroidal space within the liner. Liquid metal fills the reservoir outside said liner. Electric current is passed through the liquid metal over a conductive path linking the toroidal space to produce a toroidal magnetic field within the toroidal space about the major axis thereof. Toroidal plasma is developed within the toroidal space about the major axis thereof.

  16. Mathematical modeling plasma transport in tokamaks

    NASA Astrophysics Data System (ADS)

    Qiang, Ji

    1998-11-01

    In this work, we have applied a systematic calibration, validation and application procedure based on the methodology of mathematical modeling to international thermonuclear experimental reactor (ITER) ignition studies. The multi-mode plasma transport model used here includes a linear combination of drift wave branch and ballooning branch instabilities with two a priori uncertain constants to account for anomalous plasma transport in tokamaks. A Bayesian parameter estimation method is used including experimental calibration error/model offsets and error bar rescaling factors to determine the two uncertain constants in the transport model with quantitative confidence level estimates for the calibrated parameters, which gives two saturation levels of instabilities. This method is first tested using a gyroBohm multi-mode transport model with a pair of DIII-D discharge experimental data, and then applied to calibrating a nominal multi-mode transport model against a broad database using twelve discharges from seven different tokamaks. The calibrated transport model is then validated on five discharges from JT-60 with no adjustable constants. The results are in a good agreement with experimental data. Finally, the resulting class of multi-mode tokamak plasma transport models is applied to the transport analysis of the ignition probability in the next generation machine, ITER. The ignition probability of ITER for engineering design activity (EDA) parameters can be formally as high as 99.9% in the present context. The same probability for conceptual design activity (CDA) parameters of ITER, which has smaller size and lower current, is only 62.6%. This suggests that EDA parameters for ITER tokamak are very likely to achieve the self- sustained thermonuclear reaction, but CDA parameters are risky for the realization of ignition.

  17. Neutral-beam current drive in tokamaks

    SciTech Connect

    Devoto, R.S.

    1986-01-01

    The theory of neutral-beam current drive in tokamaks is reviewed. Experiments are discussed where neutral beams have been used to drive current directly and also indirectly through neoclassical effects. Application of the theory to an experimental test reactor is described. It is shown that neutral beams formed from negative ions accelerated to 500 to 700 keV are needed for this device.

  18. Confinement scaling and ignition in tokamaks

    SciTech Connect

    Perkins, F.W.; Sun, Y.C.

    1985-10-01

    A drift wave turbulence model is used to compute the scaling and magnitude of central electron temperature and confinement time of tokamak plasmas. The results are in accord with experiment. Application to ignition experiments shows that high density (1 to 2) . 10/sup 15/ cm/sup -3/, high field, B/sub T/ > 10 T, but low temperature T approx. 6 keV constitute the optimum path to ignition.

  19. Plasma filamentation in the Rijnhuizen tokamak RTP

    SciTech Connect

    Lopes Cardozo, N.J.; Schueller, F.C.; Barth, C.J.; Chu, C.C.; Pijper, F.J.; Lok, J.; Oomens, A.A.M. )

    1994-07-11

    Evidence for small scale magnetic structures in the Rijnhuizen tokamak RTP is presented. These are manifest through steps and peaks in the electron temperature and pressure, measured with multiposition Thomson scattering. During central electron cyclotron heating, several filaments of high pressure are found in the power deposition region. They live hundreds of microseconds. Near the sawtooth inversion radius a step'' in the temperature profile occurs. Further out, quasiperiodic structures are observed, in both Ohmic and heated discharges.

  20. Tokamaks: from A D Sakharov to the present (the 60-year history of tokamaks)

    NASA Astrophysics Data System (ADS)

    Azizov, E. A.

    2012-02-01

    The paper is prepared on the basis of the report presented at the session of the Physical Sciences Division of the Russian Academy of Sciences (RAS) at the Lebedev Physical Institute, RAS on 25 May 2011, devoted to the 90-year jubilee of Academician Andrei D Sakharov - the initiator of controlled nuclear fusion research in the USSR. The 60-year history of plasma research work in toroidal devices with a longitudinal magnetic field suggested by Andrei D Sakharov and Igor E Tamm in 1950 for the confinement of fusion plasma and known at present as tokamaks is described in brief. The recent (2006) agreement among Russia, the EU, the USA, Japan, China, the Republic of Korea, and India on the joint construction of the international thermonuclear experimental reactor (ITER) in France based on the tokamak concept is discussed. Prospects for using the tokamak as a thermonuclear (14 MeV) neutron source are examined.

  1. Development of a free-boundary tokamak equilibrium solver for advanced study of tokamak equilibria

    NASA Astrophysics Data System (ADS)

    Jeon, Young Mu

    2015-09-01

    A free-boundary Tokamak equilibrium solver (TES), developed for advanced study of tokamak equilibra, is described with two distinctive features. One is a generalized method to resolve the intrinsic axisymmetric instability, which is encountered in all equilibrium calculations with a freeboundary condition. The other is an extension to deal with a new divertor geometry such as snowflake or X divertors. For validations, the uniqueness of a solution is confirmed by the independence of variations in the computational domain, the mathematical correctness and accuracy of equilibrium profiles are checked by using a direct comparison with an analytic equilibrium known as a generalized Solov'ev equilibrium, and the governing force balance relation is tested by examining the intrinsic axisymmetric instabilities. As an application of an advanced equilibrium study, a snow-flake divertor configuration that requires a second-order zero of the poloidal magnetic flux is discussed in the circumstance of the Korea superconducting tokamak advanced research (KSTAR) coil system.

  2. Nondiffusive plasma transport at tokamak edge

    NASA Astrophysics Data System (ADS)

    Krasheninnikov, S. I.

    2000-10-01

    Recent findings show that cross field edge plasma transport at tokamak edge does not necessarily obey a simple diffusive law [1], the only type of a transport model applied so far in the macroscopic modeling of edge plasma transport. Cross field edge transport is more likely due to plasma filamentation with a ballistic motion of the filaments towards the first wall. Moreover, it so fast that plasma recycles on the main chamber first wall rather than to flow into divertor as conventional picture of edge plasma fluxes suggests. Crudely speaking particle recycling wise diverted tokamak operates in a limiter regime due to fast anomalous non-diffusive cross field plasma transport. Obviously that this newly found feature of edge plasma anomalous transport can significantly alter a design of any future reactor relevant tokamaks. Here we present a simple model describing the motion of the filaments in the scrape off layer and discuss it implications for experimental observations. [1] M. Umansky, S. I. Krasheninnikov, B. LaBombard, B. Lipschultz, and J. L. Terry, Phys. Plasmas 6 (1999) 2791; M. Umansky, S. I. Krasheninnikov, B. LaBombard and J. L. Terry, Phys. Plasmas 5 (1998) 3373.

  3. ADX - Advanced Divertor and RF Tokamak Experiment

    NASA Astrophysics Data System (ADS)

    Greenwald, Martin; Labombard, Brian; Bonoli, Paul; Irby, Jim; Terry, Jim; Wallace, Greg; Vieira, Rui; Whyte, Dennis; Wolfe, Steve; Wukitch, Steve; Marmar, Earl

    2015-11-01

    The Advanced Divertor and RF Tokamak Experiment (ADX) is a design concept for a compact high-field tokamak that would address boundary plasma and plasma-material interaction physics challenges whose solution is critical for the viability of magnetic fusion energy. This device would have two crucial missions. First, it would serve as a Divertor Test Tokamak, developing divertor geometries, materials and operational scenarios that could meet the stringent requirements imposed in a fusion power plant. By operating at high field, ADX would address this problem at a level of power loading and other plasma conditions that are essentially identical to those expected in a future reactor. Secondly, ADX would investigate the physics and engineering of high-field-side launch of RF waves for current drive and heating. Efficient current drive is an essential element for achieving steady-state in a practical, power producing fusion device and high-field launch offers the prospect of higher efficiency, better control of the current profile and survivability of the launching structures. ADX would carry out this research in integrated scenarios that simultaneously demonstrate the required boundary regimes consistent with efficient current drive and core performance.

  4. ECH on the MTX (Microwave Tokamak Experiment)

    SciTech Connect

    Stallard, B.W.; Byers, J.A.; Hooper, E.B.; Makowski, M.A.; Meassick, S.; Rice, B.W.; Rognlien, T.D.; Verboncoeur, J.

    1989-04-01

    The Microwave Tokamak Experiment (MTX) at LLNL is investigating the heating of high density Tokamak plasmas using an intense pulse FEL. Our first experiments, now beginning, will study the absorption and plasma heating of single FEL pulses (20 ns pulse length and peak power up to 2 GW) at a frequency of 140 GHz. A later phase of experiments also at 140 GHz will study FEL heating at 5 kHz rate for a pulse train up to 50 pulses (35 ns pulse length and peak power up to 4 GW). Future operations are planned at 250 GHz with an average power of 2 MW for a pulse train of 0.5 s. The microwave output of the FEL is transported quasi-optically to the tokamak through a window-less, evacuated pipe of 20 in. diameter, using a six mirror system. Computational modelling of the non-linear absorption for the MTX geometry predicts single-pass absorption of 40% at a density and temperature of 1.8 /times/ 10/sup 20/m/sup /minus/3/ and 1 keV, respectively. To measure plasma microwave absorption and backscatter, diagnostics are available to measure forward and reflected power (parallel wire grid beam-splitter and mirror directional couplers) and power transmitted through the plasma (segmented calorimeter and waveguide detector). Other fast diagnostics include ECE, Thompson scattering, soft x-rays, and fast magnetic probes. 8 refs., 2 figs.

  5. Remote feedback stabilization of tokamak instabilities

    SciTech Connect

    Sen, A.K. )

    1994-05-01

    A novel remote suppressor consisting of an injected ion beam has been used for the stabilization of plasma instabilities. A collisionless curvature-driven trapped-particle instability, an [bold E][times][bold B] flute mode and an ion temperature gradient (ITG) instability have been successfully suppressed down to noise levels using this scheme. Furthermore, the first experimental demonstration of a multimode feedback stabilization with a single sensor--suppressor pair has been achieved. Two modes (an [bold E][times][bold B] flute and an ITG mode) were simultaneously stabilized with a simple state-feedback-type method where more state'' information was generated from a single-sensor Langmuir probe by appropriate signal processing. The above experiments may be considered as paradigms for controlling several important tokamak instabilities. First, feedback suppression of edge fluctuations in a tokamak with a suitable form of insulated segmented poloidal limiter sections used as Langmuir-probe-like suppressors is proposed. Other feedback control schemes are proposed for the suppression of electrostatic core fluctuations via appropriately phased ion density input from a modulated neutral beam. Most importantly, a scheme to control major disruptions in tokamaks via feedback suppression of kink (and possibly) tearing modes is discussed. This may be accomplished by using a modulated neutral beam suppressor in a feedback loop, which will supply a momentum input of appropriate phase and amplitude. Simple theoretical models predict modest levels of beam energy, current, and power.

  6. Forced Magnetic Reconnection In A Tokamak Plasma

    NASA Astrophysics Data System (ADS)

    Callen, J. D.; Hegna, C. C.

    2015-11-01

    The theory of forced magnetic field reconnection induced by an externally imposed resonant magnetic perturbation usually uses a sheared slab or cylindrical magnetic field model and often focuses on the potential time-asymptotic induced magnetic island state. However, tokamak plasmas have significant magnetic geometry and dynamical plasma toroidal rotation screening effects. Also, finite ion Larmor radius (FLR) and banana width (FBW) effects can damp and thus limit the width of a nascent magnetic island. A theory that is more applicable for tokamak plasmas is being developed. This new model of the dynamics of forced magnetic reconnection considers a single helicity magnetic perturbation in the tokamak magnetic field geometry, uses a kinetically-derived collisional parallel electron flow response, and employs a comprehensive dynamical equation for the plasma toroidal rotation frequency. It is being used to explore the dynamics of bifurcation into a magnetically reconnected state in the thin singular layer around the rational surface, evolution into a generalized Rutherford regime where the island width exceeds the singular layer width, and assess the island width limiting effects of FLR and FBW polarization currents. Support by DoE grants DE-FG02-86ER53218, DE-FG02-92ER54139.

  7. Edge-localized-modes in tokamaks

    SciTech Connect

    Leonard, A. W.

    2014-09-15

    Edge-localized-modes (ELMs) are a ubiquitous feature of H-mode in tokamaks. When gradients in the H-mode transport barrier grow to exceed the MHD stability limit the ELM instability grows explosively, rapidly transporting energy and particles onto open field lines and material surfaces. Though ELMs provide additional particle and impurity transport through the H-mode transport barrier, enabling steady operation, the resulting heat flux transients to plasma facing surfaces project to large amplitude in future low collisionality burning plasma tokamaks. Measurements of the ELM heat flux deposition onto material surfaces in the divertor and main chamber indicate significant broadening compared to inter-ELM heat flux, with a timescale for energy deposition that is consistent with sonic ion flow and numerical simulation. Comprehensive ELM simulation is highlighting the important physics processes of ELM transport including parallel transport due to magnetic reconnection and turbulence resulting from collapse of the H-mode transport barrier. Encouraging prospects for ELM control and/or suppression in future tokamaks include intrinsic modes of ELM free operation, ELM triggering with frequent small pellet injection and the application of 3D magnetic fields.

  8. Edge-localized-modes in tokamaks

    DOE PAGES

    Leonard, Anthony W.

    2014-09-11

    Edge-localized-modes (ELMs) are a ubiquitous feature of H-mode in tokamaks. When gradients in the H-mode transport barrier grow to exceed the MHD stability limit the ELM instability grows explosively rapidly transporting energy and particles onto open field lines and material surfaces. Though ELMs provide additional particle and impurity transport through the H-mode transport barrier, enabling steady operation, the resulting heat flux transients to plasma facing surfaces project to large amplitude in future low collisionality burning plasma tokamaks. Measurements of the ELM heat flux deposition onto material surfaces in the divertor and main chamber indicate significant broadening compared to inter-ELM heatmore » flux, with a timescale for energy deposition that is consistent with sonic ion flow and numerical simulation. Comprehensive ELM simulation is highlighting the important physics processes of ELM transport including parallel transport due to magnetic reconnection and turbulence resulting from collapse of the H-mode transport barrier. As a result, encouraging prospects for ELM control and/or suppression in future tokamaks include intrinsic modes of ELM free operation, ELM triggering with frequent small pellet injection and the application of 3D magnetic fields.« less

  9. Edge-localized-modes in tokamaks

    SciTech Connect

    Leonard, Anthony W.

    2014-09-11

    Edge-localized-modes (ELMs) are a ubiquitous feature of H-mode in tokamaks. When gradients in the H-mode transport barrier grow to exceed the MHD stability limit the ELM instability grows explosively rapidly transporting energy and particles onto open field lines and material surfaces. Though ELMs provide additional particle and impurity transport through the H-mode transport barrier, enabling steady operation, the resulting heat flux transients to plasma facing surfaces project to large amplitude in future low collisionality burning plasma tokamaks. Measurements of the ELM heat flux deposition onto material surfaces in the divertor and main chamber indicate significant broadening compared to inter-ELM heat flux, with a timescale for energy deposition that is consistent with sonic ion flow and numerical simulation. Comprehensive ELM simulation is highlighting the important physics processes of ELM transport including parallel transport due to magnetic reconnection and turbulence resulting from collapse of the H-mode transport barrier. As a result, encouraging prospects for ELM control and/or suppression in future tokamaks include intrinsic modes of ELM free operation, ELM triggering with frequent small pellet injection and the application of 3D magnetic fields.

  10. The Spherical Tokamak MEDUSA for Mexico

    NASA Astrophysics Data System (ADS)

    Ribeiro, C.; Salvador, M.; Gonzalez, J.; Munoz, O.; Tapia, A.; Arredondo, V.; Chavez, R.; Nieto, A.; Gonzalez, J.; Garza, A.; Estrada, I.; Jasso, E.; Acosta, C.; Briones, C.; Cavazos, G.; Martinez, J.; Morones, J.; Almaguer, J.; Fonck, R.

    2011-10-01

    The former spherical tokamak MEDUSA (Madison EDUcation Small Aspect.ratio tokamak, R < 0.14m, a < 0.10m, BT < 0.5T, Ip < 40kA, 3ms pulse) is currently being recomissioned at the Universidad Autónoma de Nuevo León, Mexico, as part of an agreement between the Faculties of Mech.-Elect. Eng. and Phy. Sci.-Maths. The main objective for having MEDUSA is to train students in plasma physics & technical related issues, aiming a full design of a medium size device (e.g. Tokamak-T). Details of technical modifications and a preliminary scientific programme will be presented. MEDUSA-MX will also benefit any developments in the existing Mexican Fusion Network. Strong liaison within national and international plasma physics communities is expected. New activities on plasma & engineering modeling are expected to be developed in parallel by using the existing facilities such as a multi-platform computer (Silicon Graphics Altix XE250, 128G RAM, 3.7TB HD, 2.7GHz, quad-core processor), ancillary graph system (NVIDIA Quadro FE 2000/1GB GDDR-5 PCI X16 128, 3.2GHz), and COMSOL Multiphysics-Solid Works programs.

  11. Interactive, multiobjective Bayesian optimization of tokamak scenarios

    NASA Astrophysics Data System (ADS)

    Urban, Jakub; Artaud, Jean-François

    2016-10-01

    Bayesian optimization is applied to tokamak scenario optimizations. The key advantages are 1) a reduced number of objective function evaluations, 2) no need for derivatives, and 3) the possibility to include a prior knowledge. This is of a great value for optimizing tokamak scenarios, where several (competing) objectives with often unknown magnitudes exist and the number of parameters is large (>10). The first two properties imply that Bayesian optimization is well suited for heavy, complex objective functions. Reusing previous iterations as priors for next optimization steps effectively enables interactive, multiobjective optimizations, regardless of whether a human decision maker is included or not. We show that these features make Bayesian optimization an outstanding tool for optimizing tokamak scenarios. Objective functions and constraints, targeting, e.g., fusion gain, flux consumption, coils currents limits or q-profile, can be assembled interactively. The optimized parameter vector may include actuators like plasma current or heating waveforms. We demonstrate the capabilities on optimizing ITER and DEMO-like scenarios, simulated by the METIS code.

  12. Tokamak Physics Experiment diagnostic plans (invited)

    NASA Astrophysics Data System (ADS)

    Medley, S. S.

    1995-01-01

    A superconducting Tokamak Physics Experiment (TPX) whose mission is to develop the scientific basis for a compact and continuously operating tokamak fusion reactor is being designed by an integrated U.S. national team. Key physics features such as strong shaping, a double-null poloidal divertor, full noninductive current drive, and current profile control capability will be used to explore improvements in energy confinement and beta limit scaling in high-aspect-ratio plasmas with a high bootstrap current fraction. Steady-state operation of TPX permits these studies to be extended to time scales significantly exceeding the global current-relaxation time and the plasma-wall equilibrium time. The diagnostic requirements are determined by the TPX mission and supporting objectives, such as optimization of plasma performance through active control of the current profile and of the plasma-wall interactions. Diagnostic measurements are needed to characterize the plasma behavior over the full range of conventional tokamak plasma parameters with appropriate spatial and temporal resolution as well as for control and monitoring of aspects of the machine operation such as the plasma position and shape, plasma current, vacuum vessel currents, electron density and temperature, and the divertor and limiter temperatures. In addition, several diagnostic capabilities that are especially critical for the TPX project will be discussed.

  13. LHCD Scenarios for Spherical Tokamak Plasmas

    SciTech Connect

    Takase, Y.; Ejiri, A.; Oosako, T.; Bonoli, P. T.; Wright, J. C.

    2007-09-28

    Noninductive plasma current start-up and sustainment are crucial issues for spherical tokamak reactors and other applications such as component test facility. It is widely recognized that the lower hybrid wave (the slow wave), which is most efficient in driving current, is not accessible to the core of a fully developed spherical tokamak plasma with very high dielectric constant. However, it may be useful in the initial plasma current ramp-up phase while the density is still low, where it is not practical to use other methods of noninductive current drive. Such a possibility is investigated theoretically for planned experiments on the TST-2 spherical tokamak at the University of Tokyo. The transmitters previously used for FWCD experiments on JFT-2M (200 MHz) are being prepared for this experiment. The combline antenna used for JFT-2M has been modified for use in TST-2. This antenna will be used to excite a unidirectional fast wave traveling in the toroidal direction with a toroidal mode number of 12 (corresponding to an initial parallel index of refraction of about 5). The fast wave can mode convert to the lower hybrid wave and drive current under some conditions. Examination of the dispersion relation indicates that there may be a suitable regime at relatively high field (0.3 T) and low density (<1x10{sup 19} m{sup -3})

  14. Spherical tokamaks with plasma centre-post

    NASA Astrophysics Data System (ADS)

    Ribeiro, Celso

    2013-10-01

    The metal centre-post (MCP) in tokamaks is a structure which carries the total toroidal field current and also houses the Ohmic heating solenoid in conventional or low aspect ratio (Spherical)(ST) tokamaks. The MCP and solenoid are critical components for producing the toroidal field and for the limited Ohmic flux in STs. Constraints for a ST reactor related to these limitations lead to a minimum plasma aspect ratio of 1.4 which reduces the benefit of operation at higher betas in a more compact ST reactor. Replacing the MCP is of great interest for reactor-based ST studies since the device is simplified, compactness increased, and maintenance reduced. An experiment to show the feasibility of using a plasma centre-post (PCP) is being currently under construction and involves a high level of complexity. A preliminary study of a very simple PCP, which is ECR(Electron Cyclotron Resonance)-assisted and which includes an innovative fuelling system based on pellet injection, has recently been reported. This is highly suitable for an ultra-low aspect ratio tokamak (ULART) device. Advances on this PCP ECR-assisted concept within a ULART and the associated fuelling system are presented here, and will include the field topology for the PCP ECR-assisted scheme, pellet ablation modeling, and a possible global equilibrium simulation. VIE-ITCR, IAEA-CRP contr.17592, National Instruments-Costa Rica.

  15. A simulation study of a controlled tokamak plasma

    NASA Astrophysics Data System (ADS)

    Fujii, N.; Niwa, Y.

    1980-03-01

    A tokamak circuit theory, including results of numerical simulation studies, is applied to a control system synthesized for a Joule heated tokamak plasma. The treatment is similar to that of Ogata and Ninomiya (1979) except that in this case a quadrupole field coil current is considered coexisting with image induced on a vacuum chamber.

  16. Advanced tokamak operating modes in TPX and ITER

    SciTech Connect

    Nevins, W.M.

    1994-12-31

    A program is described to develop the advanced tokamak physics required for an economic steady-state fusion reactor on existing (short-pulse) tokamak experiments; to extend these operating modes to long-pulse on TPX; and finally to demonstrate them in a long-pulse D-T plasma on ITER.

  17. Numerical investigations of plasma parameters in the COMPASS tokamak

    SciTech Connect

    Havlickova, E.; Zagorski, R.; Panek, R.

    2008-09-15

    A numerical investigation of plasma parameters in a diverter configuration of COMPASS tokamak is presented. The plasma parameters in the device are analyzed in the frame of the self-consistent description of the central plasma and edge region. The possibility of achieving high recycling and detached regimes in the boundary layer of the COMPASS tokamak is discussed.

  18. Fokker-Planck/Transport model for neutral beam driven tokamaks

    SciTech Connect

    Killeen, J.; Mirin, A.A.; McCoy, M.G.

    1980-01-01

    The application of nonlinear Fokker-Planck models to the study of beam-driven plasmas is briefly reviewed. This evolution of models has led to a Fokker-Planck/Transport (FPT) model for neutral-beam-driven Tokamaks, which is described in detail. The FPT code has been applied to the PLT, PDX, and TFTR Tokamaks, and some representative results are presented.

  19. Physics design requirements for the Tokamak Physics Experiment (TPX)

    SciTech Connect

    Neilson, G.H.; Goldston, R.J.; Jardin, S.C.; Reiersen, W.T.; Nevins, W.M.; Porkolab, M.; Ulrickson, M.

    1993-11-01

    The design of TPX is driven by physics requirements that follow from its mission. The tokamak and heating systems provide the performance and profile controls needed to study advanced steady state tokamak operating modes. The magnetic control systems provide substantial flexibility for the study of regimes with high beta and bootstrap current. The divertor is designed for high steady state power and particle exhaust.

  20. Advanced tokamak operating modes in TPX and ITER

    NASA Astrophysics Data System (ADS)

    Nevins, W. M.

    1994-09-01

    A program is described to develop the advanced tokamak physics required for an economic steady-state fusion reactor on existing (short-pulse) tokamak experiments; to extend these operating modes to long-pulse on TPX; and finally to demonstrate them in a long-pulse D-T plasma on ITER.

  1. Progress and prospects in understanding the physics of tokamak experiments

    SciTech Connect

    Hutchinson, I.

    1992-12-01

    A whistle-stop tour of the diverse physics of tokamak plasma confinement. This talk will illustrate the way in which fusion research on tokamaks has led to important and interesting physics results, and discuss some of the scientific challenges still ahead before fusion`s potential can be established.

  2. Recent progress on the Compact Ignition Tokamak (CIT)

    SciTech Connect

    Ignat, D.W.

    1987-01-01

    This report describes work done on the Compact Ignition Tokamak (CIT), both at the Princeton Plasma Physics Laboratory (PPPL) and at other fusion laboratories in the United States. The goal of CIT is to reach ignition in a tokamak fusion device in the mid-1990's. Scientific and engineering features of the design are described, as well as projected cost and schedule.

  3. Tokamak Physics Experiment (TPX) power supply design and development

    SciTech Connect

    Neumeyer, C.; Bronner, G.; Lu, E.; Ramakrishnan, S.

    1995-04-01

    The Tokamak Physics Experiment (TPX) is an advanced tokamak project aimed at the production of quasi-steady state plasmas with advanced shape, heating, and particle control. TPX is to be built at the Princeton Plasma Physics Laboratory (PPPL) using many of the facilities from the Tokamak Fusion Test Reactor (TFTR). TPX will be the first tokamak to utilize superconducting (SC) magnets in both the toroidal field (TF) and poloidal field (PF) systems. This new feature requires a departure from the traditional tokamak power supply schemes. This paper describes the plan for the adaptation of the PPPL/FTR power system facilities to supply TPX. Five major areas are addressed, namely the AC power system, the TF, PF and Fast Plasma Position Control (FPPC) power supplies, and quench protection for the TF and PF systems. Special emphasis is placed on the development of new power supply and protection schemes.

  4. Hybrid Fusion: The Only Viable Development Path for Tokamaks?

    NASA Astrophysics Data System (ADS)

    Manheimer, Wallace

    2009-03-01

    The world needs a great deal of carbon free energy, and soon, for civilization to continue. Fusion's goal is to develop such a carbon free energy source. For the last 4 decades, tokamaks have been the best magnetic fusion has to offer. But what if its development stops short of commercial fusion? This paper introduces `conservative design principles' for tokamaks. These are very simple, are reasonably based in theory, and have always constrained tokamak operation. Assuming they continue to do so, it is unlikely that tokamaks will ever make it as commercial reactors. This is independent of their confinement properties. However because of the large additional gain in hybrid fusion, tokamaks reactors look like they can make it as hybrid fuel producers, and provide large scale power by mid century or shortly thereafter.

  5. New arylpiperazinylalkyl derivatives of 8-alkoxy-purine-2,6-dione and dihydro[1,3]oxazolo[2,3-f]purinedione targeting the serotonin 5-HT1A /5-HT2A /5-HT7 and dopamine D2 receptors.

    PubMed

    Chłoń-Rzepa, Grażyna; Zagórska, Agnieszka; Bucki, Adam; Kołaczkowski, Marcin; Pawłowski, Maciej; Satała, Grzegorz; Bojarski, Andrzej J; Partyka, Anna; Wesołowska, Anna; Pękala, Elżbieta; Słoczyńska, Karolina

    2015-04-01

    To obtain potential antidepressants and/or antipsychotics, a series of new long-chain arylpiperazine derivatives of 8-alkoxy-purine-2,6-dione (10-24) and dihydro[1,3]oxazolo[2,3-f]purinedione (30-34) were synthesized and their serotonin (5-HT1A , 5-HT2A , 5-HT6 , 5-HT7 ) and dopamine (D2 ) receptor affinities were determined. The study allowed the identification of some potent 5-HT1A /5-HT7 /D2 ligands with moderate affinity for 5-HT2A sites. The binding mode of representative compounds from both chemical classes (11 and 31) in the site of 5-HT1A receptor was analyzed in computational studies. In functional in vitro studies, the selected compounds 15 and 16 showed antagonistic properties for the evaluated receptors. 8-Methoxy-7-{4-[4-(2-methoxyphenyl)-piperazin-1-yl]-butyl}-1,3-dimethyl-purine-2,6-dione (15) showed a lack of activity in terms and under the conditions of the forced swim, four plate and amphetamine-induced hyperactivity tests in mice, probably as a result of its high first pass effect in the liver.

  6. Mathematical modeling plasma transport in tokamaks

    SciTech Connect

    Quiang, Ji

    1997-01-01

    In this work, the author applied a systematic calibration, validation and application procedure based on the methodology of mathematical modeling to international thermonuclear experimental reactor (ITER) ignition studies. The multi-mode plasma transport model used here includes a linear combination of drift wave branch and ballooning branch instabilities with two a priori uncertain constants to account for anomalous plasma transport in tokamaks. A Bayesian parameter estimation method is used including experimental calibration error/model offsets and error bar rescaling factors to determine the two uncertain constants in the transport model with quantitative confidence level estimates for the calibrated parameters, which gives two saturation levels of instabilities. This method is first tested using a gyroBohm multi-mode transport model with a pair of DIII-D discharge experimental data, and then applied to calibrating a nominal multi-mode transport model against a broad database using twelve discharges from seven different tokamaks. The calibrated transport model is then validated on five discharges from JT-60 with no adjustable constants. The results are in a good agreement with experimental data. Finally, the resulting class of multi-mode tokamak plasma transport models is applied to the transport analysis of the ignition probability in a next generation machine, ITER. A reference simulation of basic ITER engineering design activity (EDA) parameters shows that a self-sustained thermonuclear burn with 1.5 GW output power can be achieved provided that impurity control makes radiative losses sufficiently small at an average plasma density of 1.2 X 1020/m3 with 50 MW auxiliary heating. The ignition probability of ITER for the EDA parameters, can be formally as high as 99.9% in the present context. The same probability for concept design activity (CDA) parameters of ITER, which has smaller size and lower current, is only 62.6%.

  7. Halo Current Simulations for Tokamak Plasmas

    NASA Astrophysics Data System (ADS)

    Paccagnella, R.; Strauss, H. R.; Torasso, R.; Park, W.; Jardin, S.; Breslau, J.; Pletzer, A.; Fu, G. Y.; Sugiyama, L.

    2003-10-01

    A 3D MHD multi-level code, M3D [1], has been used in this work to simulate a tokamak Vertical Displacement Event (VDE) scenario. These simulations are interesting both from the point of view of gaining physical insight on the plasma dynamics during a VDE or a disruption event and are also relevant in order to estimate the amount of non-axisymmetric torques on the vacuum chamber -- a particular important issue for next generation tokamak (like ITER) design. In this work we numerically simulate a single-null ITER-like plasma evolution using a nonlinear single-fluid model interfaced through thin shell resistive wall boundary conditions to the external vacuum solution. A complete reconstruction of the magnetic field time evolution is therefore possible in the plasma and vacuum regions. Work is in progress to benchmark the code with 2D simulations done with the TSC [2] code. We have previously verified the expected linear scaling of the vertical instability growth rate with the wall resistivity. We are studying the effect of different initial tokamak equilibria (i.e. with different q profiles) on the instability growth rate. We are also studying the nonlinear evolution of the VDE for different fault-scenarios involving the relative timing of the disruptive thermal quench and the loss of vertical control, and for different assumptions regarding the conductivity and width of the plasma halo region. An output of this work is a prediction of the Toroidal Peaking Factor (TPF) [3] of the halo currents and associated vessel forces characterizing the non-axisymmetric events. This work was supported in part by the USDOE. [1] PARK, W., et al., Phys.Plasmas 6, 1796 (1999). [2] Sayer, R.O., Peng, Y-K. M., Jardin, S. C., Kellman, A. G., Wesley, J. C., Nuclear Fusion 33, 969 (1993). [3] Pomphrey, N., Bialek, J., Park, W., Nuclear Fusion 38, 449 (1998).

  8. Industry roles in the Tokamak Physics Experiment

    SciTech Connect

    Thomassen, K.; Lang, D.; Schmidt, J.; Burger, A.

    1995-06-01

    There are several distinguishing features of the Tokamak Physics Experiment (TPX) to be found in the TPX program and in the organizations for constructing and operating the machine. Programmatically, TPX addresses several issues critical to the viability of magnetic fusion power plants. Organizationally, it is a multi-institutional partnership to construct and operate the machine and carry out its program mission. An important part of the construction partnership is the integrated industrial responsibility for design, R&D, and construction. The TPX physics design takes advantage of recent research on advanced tokamak operating modes achieved for time scales of the order of seconds that are consistent with continuous operation. This synergism of high performance (higher power density) modes with plasma current driven mostly by internal pressure (boot-strap effect) points toward tokamak power plants that will be cost-competitive and operate continuously. A large fraction of the project is subcontracted to industry. By policy, these contracts are at a high level in the project breakdown of work, giving contractors much of the overall responsibility for a given major system. That responsibility often includes design and R&D in addition to the fabrication of the system in question. Each contract is managed through one of three national laboratories: PPPL, LLNL, and ORNL. Separate contracts for system integration and construction management round out the industry involvement in the project. This integrated, major responsibility attracts high-level corporate attention within each company, which are major corporations with long-standing interest in fusion. Through the contracts already established on the TPX project, a new standard for industry involvement in fusion has been set, and these industries will be well prepared for future fusion projects.

  9. Electrostatic analysis of the tokamak edge plasma

    SciTech Connect

    Motley, R.W.

    1981-07-01

    The intrusion of an equipotential poloidal limiter into the edge plasma of a circular tokamak discharge distorts the axisymmetry in two ways: (1) it (partially) shorts out the top-to-bottom Pfirsch-Schlueter driving potentials, and (2) it creates zones of back current flow into the limiter. The resulting boundary mismatch between the outer layers and the inner axisymmetric Pfirsch-Schlueter layer provides free energy to drive the edge plasma unstable. Special limiters are proposed to symmetrize the edge plasma and thereby reduce the electrical and MHD activity in the boundary layer.

  10. Tokamak physics experiment: Diagnostic windows study

    SciTech Connect

    Merrigan, M.; Wurden, G.A.

    1995-11-01

    We detail the study of diagnostic windows and window thermal stress remediation in the long-pulse, high-power Tokamak Physics Experiment (TPX) operation. The operating environment of the TPX diagnostic windows is reviewed, thermal loads on the windows estimated, and cooling requirements for the windows considered. Applicable window-cooling technology from other fields is reviewed and its application to the TPX windows considered. Methods for TPX window thermal conditioning are recommended, with some discussion of potential implementation problems provided. Recommendations for further research and development work to ensure performance of windows in the TPX system are presented.

  11. Self-Organized Stationary States of Tokamaks

    DOE PAGES

    Jardin, S. C.; Ferraro, N.; Krebs, I.

    2015-11-17

    We demonstrate that in a 3D resistive magnetohydrodynamic (MHD) simulation, for some parameters it is possible to form a stationary state in a tokamak where a saturated interchange mode in the center of the discharge drives a near helical flow pattern that acts to non-linearly sustain the configuration by adjusting the central loop voltage through a dynamo action. This could explain the physical mechanism for maintaining stationary non-sawtoothing “hybrid” discharges, often referred to as “flux-pumping”.

  12. An efficient transport solver for tokamak plasmas

    DOE PAGES

    Park, Jin Myung; Murakami, Masanori; St. John, H. E.; ...

    2017-01-03

    A simple approach to efficiently solve a coupled set of 1-D diffusion-type transport equations with a stiff transport model for tokamak plasmas is presented based on the 4th order accurate Interpolated Differential Operator scheme along with a nonlinear iteration method derived from a root-finding algorithm. Here, numerical tests using the Trapped Gyro-Landau-Fluid model show that the presented high order method provides an accurate transport solution using a small number of grid points with robust nonlinear convergence.

  13. Overview of the Compact Ignition tokamak

    SciTech Connect

    Flanagan, C. A.; Peng, Yueng Kay Martin

    1986-01-01

    The Compact Ignition Tokamak (CIT) mission is to achieve ignition and provide the capability to experimentally study burning plasma behavior. A national team has developed a baseline concept including definition of the necessary research and development. The baseline concept satisfies the physics performance objectives established for the project and complies with defined design specifications. To ensure that the mission is achieved, the design requires large magnetic fields on axis (10 T) and use of large plasma currents (10 MA). The design is capable of accommodating significant auxiliary heating to enter the ignited regime. The CIT is designed to operate in plasma parameter regimes that a are directly relevant to future fusion power reactors.

  14. Energetic particles in spherical tokamak plasmas

    NASA Astrophysics Data System (ADS)

    McClements, K. G.; Fredrickson, E. D.

    2017-05-01

    Spherical tokamaks (STs) typically have lower magnetic fields than conventional tokamaks, but similar mass densities. Suprathermal ions with relatively modest energies, in particular beam-injected ions, consequently have speeds close to or exceeding the Alfvén velocity, and can therefore excite a range of Alfvénic instabilities which could be driven by (and affect the behaviour of) fusion α-particles in a burning plasma. STs heated with neutral beams, including the small tight aspect ratio tokamak (START), the mega amp spherical tokamak (MAST), the national spherical torus experiment (NSTX) and Globus-M, have thus provided an opportunity to study toroidal Alfvén eigenmodes (TAEs), together with higher frequency global Alfvén eigenmodes (GAEs) and compressional Alfvén eigenmodes (CAEs), which could affect beam current drive and channel fast ion energy into bulk ions in future devices. In NSTX GAEs were correlated with a degradation of core electron energy confinement. In MAST pulses with reduced magnetic field, CAEs were excited across a wide range of frequencies, extending to the ion cyclotron range, but were suppressed when hydrogen was introduced to the deuterium plasma, apparently due to mode conversion at ion-ion hybrid resonances. At lower frequencies fishbone instabilities caused fast particle redistribution in some MAST and NSTX pulses, but this could be avoided by moving the neutral beam line away from the magnetic axis or by operating the plasma at either high density or elevated safety factor. Fast ion redistribution has been observed during GAE avalanches on NSTX, while in both NSTX and MAST fast ions were transported by saturated kink modes, sawtooth crashes, resonant magnetic perturbations and TAEs. The energy dependence of fast ion redistribution due to both sawteeth and TAEs has been studied in Globus-M. High energy charged fusion products are unconfined in present-day STs, but have been shown in MAST to provide a useful diagnostic of beam ion

  15. Neoclassical Transport Properties of Tokamak Plasmas

    SciTech Connect

    Weyssow, B.

    2004-03-15

    The classical transport theory is strictly valid for a plasma in a homogeneous and stationary magnetic field. In the '60, experiments have shown that this theory does not apply as a local theory of transport in Tokamaks. It was shown that global geometric characteristics of the confining elements have a strong influence on the transport. Three regimes of collisionality are characteristic of the neoclassical transport theory: the banana regime (the electronic diffusion coefficient increases starting from zero), the plateau regime (the diffusion coefficient is almost independent of the collisionality) and the Pfirsch-Schlueter regime (the electronic diffusion coefficient again increases with the collisionality)

  16. 3D MHD Simulations of Tokamak Disruptions

    NASA Astrophysics Data System (ADS)

    Woodruff, Simon; Stuber, James

    2014-10-01

    Two disruption scenarios are modeled numerically by use of the CORSICA 2D equilibrium and NIMROD 3D MHD codes. The work follows the simulations of pressure-driven modes in DIII-D and VDEs in ITER. The aim of the work is to provide starting points for simulation of tokamak disruption mitigation techniques currently in the CDR phase for ITER. Pressure-driven instability growth rates previously observed in simulations of DIIID are verified; Halo and Hiro currents produced during vertical displacements are observed in simulations of ITER with implementation of resistive walls in NIMROD. We discuss plans to exercise new code capabilities and validation.

  17. Diamagnetic flux measurement in Aditya tokamak

    SciTech Connect

    Kumar, Sameer; Jha, Ratneshwar; Lal, Praveen; Hansaliya, Chandresh; Gopalkrishna, M. V.; Kulkarni, Sanjay; Mishra, Kishore

    2010-12-15

    Measurements of diamagnetic flux in Aditya tokamak for different discharge conditions are reported for the first time. The measured diamagnetic flux in a typical discharge is less than 0.6 mWb and therefore it has required careful compensation for various kinds of pick-ups. The hardware and software compensations employed in this measurement are described. We introduce compensation of a pick-up due to plasma current of less than 20 kA in short duration discharges, in which plasma pressure gradient is supposed to be negligible. The flux measurement during radio frequency heating is also presented in order to validate compensation.

  18. Diamagnetic flux measurement in Aditya tokamak.

    PubMed

    Kumar, Sameer; Jha, Ratneshwar; Lal, Praveen; Hansaliya, Chandresh; Gopalkrishna, M V; Kulkarni, Sanjay; Mishra, Kishore

    2010-12-01

    Measurements of diamagnetic flux in Aditya tokamak for different discharge conditions are reported for the first time. The measured diamagnetic flux in a typical discharge is less than 0.6 mWb and therefore it has required careful compensation for various kinds of pick-ups. The hardware and software compensations employed in this measurement are described. We introduce compensation of a pick-up due to plasma current of less than 20 kA in short duration discharges, in which plasma pressure gradient is supposed to be negligible. The flux measurement during radio frequency heating is also presented in order to validate compensation.

  19. Energetic particles in spherical tokamak plasmas

    DOE PAGES

    McClements, K. G.; Fredrickson, E. D.

    2017-03-21

    Spherical tokamaks (STs) typically have lower magnetic fields than conventional tokamaks, but similar mass densities. Suprathermal ions with relatively modest energies, in particular beam-injected ions, consequently have speeds close to or exceeding the Alfvén velocity, and can therefore excite a range of Alfvénic instabilities which could be driven by (and affect the behaviour of) fusion α-particles in a burning plasma. STs heated with neutral beams, including the small tight aspect ratio tokamak (START), the mega amp spherical tokamak (MAST), the national spherical torus experiment (NSTX) and Globus-M, have thus provided an opportunity to study toroidal Alfvén eigenmodes (TAEs), together withmore » higher frequency global Alfvén eigenmodes (GAEs) and compressional Alfvén eigenmodes (CAEs), which could affect beam current drive and channel fast ion energy into bulk ions in future devices. In NSTX GAEs were correlated with a degradation of core electron energy confinement. In MAST pulses with reduced magnetic field, CAEs were excited across a wide range of frequencies, extending to the ion cyclotron range, but were suppressed when hydrogen was introduced to the deuterium plasma, apparently due to mode conversion at ion–ion hybrid resonances. At lower frequencies fishbone instabilities caused fast particle redistribution in some MAST and NSTX pulses, but this could be avoided by moving the neutral beam line away from the magnetic axis or by operating the plasma at either high density or elevated safety factor. Fast ion redistribution has been observed during GAE avalanches on NSTX, while in both NSTX and MAST fast ions were transported by saturated kink modes, sawtooth crashes, resonant magnetic perturbations and TAEs. The energy dependence of fast ion redistribution due to both sawteeth and TAEs has been studied in Globus-M. High energy charged fusion products are unconfined in present-day STs, but have been shown in MAST to provide a useful diagnostic of

  20. Tokamak equilibria with reversed current density.

    PubMed

    Martynov, A A; Medvedev, S Yu; Villard, L

    2003-08-22

    Observations of nearly zero toroidal current in the central region of tokamaks (the "current hole") raises the question of the existence of toroidal equilibria with very low or reversed current in the core. The solutions of the Grad-Shafranov equilibrium equation with hollow toroidal current density profile including negative current density in the plasma center are investigated. Solutions of the corresponding eigenvalue problem provide simple examples of such equilibrium configurations. More realistic equilibria with toroidal current density reversal are computed using a new equilibrium problem formulation and computational algorithm which do not assume nested magnetic surfaces.

  1. Nonlinear gyrokinetic equations for tokamak microturbulence

    SciTech Connect

    Hahm, T.S.

    1988-05-01

    A nonlinear electrostatic gyrokinetic Vlasov equation, as well as Poisson equation, has been derived in a form suitable for particle simulation studies of tokamak microturbulence and associated anomalous transport. This work differs from the existing nonlinear gyrokinetic theories in toroidal geometry, since the present equations conserve energy while retaining the crucial linear and nonlinear polarization physics. In the derivation, the action-variational Lie perturbation method is utilized in order to preserve the Hamiltonian structure of the original Vlasov-Poisson system. Emphasis is placed on the dominant physics of the collective fluctuations in toroidal geometry, rather than on details of particle orbits. 13 refs.

  2. Viscosity in the edge of tokamak plasmas

    SciTech Connect

    Stacey, W.M.

    1993-05-01

    A fluid representation of viscosity has been incorporated into a set of fluid equations that are maximally ordered in the ``short-radial-gradient-scale-length`` (srgsl) ordering that is appropriate for the edge of tokamak plasmas. The srgsl ordering raises viscous drifts and other viscous terms to leading order and fundamentally alters the character of the fluid equations. A leasing order viscous drift is identified. Viscous-driven radial particle and energy fluxes in the scrape-off layer and divertor channel are estimated to have an order unity effect in reducing radial peaking of energy fluxes transported along the field lines to divertor collector plates.

  3. Viscosity in the edge of tokamak plasmas

    NASA Astrophysics Data System (ADS)

    Stacey, W. M.

    1993-05-01

    A fluid representation of viscosity has been incorporated into a set of fluid equations that are maximally ordered in the 'short radial gradient scale length' (srgsl) ordering that is appropriate for the edge of tokamak plasmas. The srgsl ordering raises viscous drifts and other viscous terms to leading order and fundamentally alters the character of the fluid equations. A leasing order viscous drift is identified. Viscous-driven radial particle and energy fluxes in the scrape-off layer and divertor channel are estimated to have an order unity effect in reducing radial peaking of energy fluxes transported along the field lines to divertor collector plates.

  4. Self-Organized Stationary States of Tokamaks

    SciTech Connect

    Jardin, S. C.; Ferraro, N.; Krebs, I.

    2015-11-17

    We demonstrate that in a 3D resistive magnetohydrodynamic (MHD) simulation, for some parameters it is possible to form a stationary state in a tokamak where a saturated interchange mode in the center of the discharge drives a near helical flow pattern that acts to non-linearly sustain the configuration by adjusting the central loop voltage through a dynamo action. This could explain the physical mechanism for maintaining stationary non-sawtoothing “hybrid” discharges, often referred to as “flux-pumping”.

  5. Dust divertor for a tokamak fusion reactor

    SciTech Connect

    Tang, X Z; Delzanno, G L

    2009-01-01

    Micron-size tungsten particulates find equilibrium position in the magnetized plasma sheath in the normal direction of the divertor surface, but are convected poloidally and toroidally by the sonic-ion-flow drag parallel to the divertor surface. The natural circulation of dust particles in the magnetized plasma sheath can be used to set up a flowing dust shield that absorbs and exhausts most of the tokamak heat flux to the divertor. The size of the particulates and the choice of materials offer substantial room for optimization.

  6. Electrostatic Dust Detection and Removal in Tokamaks

    NASA Astrophysics Data System (ADS)

    Hensley, R.; Skinner, C. H.; Roquemore, A. L.

    2006-10-01

    The inventory of in-vessel dust particles in next-step tokamaks will increase with the rise in stored energy and pulse duration. Dust levels will need to be measured and controlled for safety reasons and to avoid plasma contamination. A novel electrostatic dust detector has been developed with a sensitivity appropriate for the carbon dust levels expected in next-step devices.^23 Higher sensitivity is desired for real-time measurements in contemporary tokamaks that have less dust. We report on results from a larger area, more sensitive detector. A 2 x 2 circuit board has two interlocking combs of copper traces spaced by 25 microns and biased at 30-50 V. The carbon test dust is delivered to the circuit board by a mesh tray vibrated at 60 Hz. The impinging dust creates a short circuit and the resulting current pulse is recorded. We will present results on the dust detection sensitivity and dust removal efficiency of these new detectors in three environments: air, vacuum, and inert gas. ^2 C. Voinier et al., J. Nucl. Mater. 346 (2005) 266-271. ^3 C. Parker et al., PPPL Report, PPPL-4169.

  7. The Spherical Tokamak MEDUSA for Costa Rica

    NASA Astrophysics Data System (ADS)

    Ribeiro, Celso; Vargas, Ivan; Guadamuz, Saul; Mora, Jaime; Ansejo, Jose; Zamora, Esteban; Herrera, Julio; Chaves, Esteban; Romero, Carlos

    2012-10-01

    The former spherical tokamak (ST) MEDUSA (Madison EDUcation Small Aspect.ratio tokamak, R<0.14m, a<0.10m, BT<0.5T, Ip<40kA, 3ms pulse)[1] is in a process of donation to Costa Rica Institute of Technology. The main objective of MEDUSA is to train students in plasma physics /technical related issues which will help all tasks of the very low aspect ratio stellarator SCR-1(A≡R/>=3.6, under design[2]) and also the ongoing activities in low temperature plasmas. Courses in plasma physics at undergraduate and post-graduate joint programme levels are regularly conducted. The scientific programme is intend to clarify several issues in relevant physics for conventional and mainly STs, including transport, heating and current drive via Alfv'en wave, and natural divertor STs with ergodic magnetic limiter[3,4]. [1] G.D.Garstka, PhD thesis, University of Wisconsin at Madison, 1997 [2] L.Barillas et al., Proc. 19^th Int. Conf. Nucl. Eng., Japan, 2011 [3] C.Ribeiro et al., IEEJ Trans. Electrical and Electronic Eng., 2012(accepted) [4] C.Ribeiro et al., Proc. 39^th EPS Conf. Contr. Fusion and Plasma Phys., Sweden, 2012

  8. Constrained ripple optimization of Tokamak bundle divertors

    SciTech Connect

    Hively, L.M.; Rome, J.A.; Lynch, V.E.; Lyon, J.F.; Fowler, R.H.; Peng, Y-K.M.; Dory, R.A.

    1983-02-01

    Magnetic field ripple from a tokamak bundle divertor is localized to a small toroidal sector and must be treated differently from the usual (distributed) toroidal field (TF) coil ripple. Generally, in a tokamak with an unoptimized divertor design, all of the banana-trapped fast ions are quickly lost due to banana drift diffusion or to trapping between the 1/R variation in absolute value vector B ..xi.. B and local field maxima due to the divertor. A computer code has been written to optimize automatically on-axis ripple subject to these constraints, while varying up to nine design parameters. Optimum configurations have low on-axis ripple (<0.2%) so that, now, most banana-trapped fast ions are confined. Only those ions with banana tips near the outside region (absolute value theta < or equal to 45/sup 0/) are lost. However, because finite-sized TF coils have not been used in this study, the flux bundle is not expanded.

  9. TIBER: tokamak ignition/burn experimental research

    SciTech Connect

    Henning, C.D.; Logan, B.G.; Barr, W.L.; Bulmer, R.H.; Doggett, J.N.; Johnston, B.M.; Hoard, R.W.; Lee, J.D.; Miller, J.R.; Slack, D.S.; Schultz, J.H.

    1985-11-01

    As part of a continuing effort by the Office of Fusion Energy to define an ignition experiment, a superconducting tokamak has been designed with thin neutron shielding and aggressive magnet and plasma parameters. By so minimizing the inner radial dimensions of the tokamak center post, coil, and shielding region, the plasma major radius is reduced, with a corresponding reduction in device costs. The peak nuclear-heating rate in the superconducting TF coils is 22 mW/cmT, which results in a steady heat load of 50 kW to the cryogenic system. Fast-wave, lower-hybrid heating would be used to induce a 10-MA current in a moderate density plasma. Then pellet fueling would raise the density to achieve ignition as the current decays in a few hundred seconds. Steady-state current drive in subignited conditions permits a 0.8 MW/mS average wall loading to study plasma and nuclear engineering effects. 10 refs., 6 figs., 3 tabs.

  10. Magnetic diagnostics for the lithium tokamak experiment.

    PubMed

    Berzak, L; Kaita, R; Kozub, T; Majeski, R; Zakharov, L

    2008-10-01

    The lithium tokamak experiment (LTX) is a spherical tokamak with R(0)=0.4 m, a=0.26 m, B(TF) approximately 3.4 kG, I(P) approximately 400 kA, and pulse length approximately 0.25 s. The focus of LTX is to investigate the novel low-recycling lithium wall operating regime for magnetically confined plasmas. This regime is reached by placing an in-vessel shell conformal to the plasma last closed flux surface. The shell is heated and then coated with liquid lithium. An extensive array of magnetic diagnostics is available to characterize the experiment, including 80 Mirnov coils (single and double axis, internal and external to the shell), 34 flux loops, 3 Rogowskii coils, and a diamagnetic loop. Diagnostics are specifically located to account for the presence of a secondary conducting surface and engineered to withstand both high temperatures and incidental contact with liquid lithium. The diagnostic set is therefore fabricated from robust materials with heat and lithium resistance and is designed for electrical isolation from the shell and to provide the data required for highly constrained equilibrium reconstructions.

  11. The ARIES-I Tokamak Reactor Study

    SciTech Connect

    Najmabadi, F; Peng, Yueng Kay Martin

    1991-01-01

    The ARIES research program is a multi-institutional effort to develop several visions of tokamak reactors with enhanced economic, safety, and environmental features. Three ARIES visions are currently planned for the ARIES program. The ARIES-I design si a DT-burning reactor based on modest extrapolation from the present tokamak physics data base; ARIES-II is a DT-burning reactor which will employ potential advances in physics; and ARIES-III is a conceptual D-{sup 3}He reactor. The first design to be completed is ARIES-I, a 1000 MWe power reactor. The key features of ARIES-I are: (1) a passively safe and low environmental impact design because of choice of low activation material throughout the fusion power core, (2) an acceptable cost of electricity, (3) a plasma with performance as close as possible to present-day experimental achievements, (4) a high performance, low activation, SiC composite blanket cooled by He, and (5) an advanced Rankine power cycle as planned for near term coal-fired plants. The ARIES-I research has also identified key physics and technology areas with the highest leverage for achieving attractive fusion power system.

  12. RF Wave Propagation and Scattering in Tokamaks

    NASA Astrophysics Data System (ADS)

    Horton, Wendell; Goniche, Marc; Arefiev, Alex; Peysson, Yves; Ekedahl, Annika; InstituteFusion Studies Collaboration; IRFM CEA Collaboration

    2016-10-01

    The propagation, scattering and absorption of the lower hybrid and electron cyclotron RF waves used to control fusion plasmas is reviewed. Drift wave turbulence driven by the steep ion and electron temperature gradients in H-mode divertor tokamaks produces strong scattering of the RF waves used for heating and plasma currents drive Both the 3-5GHz lower-hybrid (LH) and the 170GHZ electron cyclotron (EC) waves experience scattering and diffraction as propagating through the statistically complex density of the plasma. Ray equations are used to calculate the spread of the rays and the associated change in the parallel phase, polarization and group velocity of the RF waves in the propagation through the fusion plasma. A Fokker Planck equation for the phase space of the RF plasmons is one method to describe the spread of the RF wave power in the complex geometry of a divertor tokamak using the ray tracing codes. The evolution of the electron distribution function from the resonant electron-wave interactions is summarized for several scenarios. The resulting X-ray spectrum is broaden giving better agreement with the measured X-ray spectrum than that calculated in the absence of the turbulent scattering of the RF waves. M. Goniche et al., and Tore Supra Team, Phys. Plasmas 21, 2014.

  13. The external kink mode in diverted tokamaks

    DOE PAGES

    Turnbull, Alan D.; Hanson, Jeremy M.; Turco, Francesca; ...

    2016-06-16

    Here, an explanation is provided for the disruptive instability in diverted tokamaks when the safety factor at the 95% poloidal flux surface, q95, is driven below 2.0. The instability is a resistive kink counterpart to the current-driven ideal mode that traditionally explained the corresponding disruption in limited cross-sections when qedge, the safety factor at the outermost closed flux surface, lies just below a rational value. Experimentally, external kink modes are observed in limiter configurations as the current in a tokamak is ramped up and qedge decreases through successive rational surfaces. For qedge < 2, the instability is always encountered andmore » is highly disruptive. However, diverted plasmas, in which qedge is formally infinite in the magnetohydrodynamic (MHD) model, have presented a longstanding difficulty since the theory would predict stability, yet, the disruptive limit occurs in practice when q95, reaches 2. It is shown from numerical calculations that a resistive kink mode is linearly destabilized by the rapidly increasing resistivity at the plasma edge when q95 < 2, but qedge >> 2. The resistive kink behaves much like the ideal kink with predominantly kink or interchange parity and no real sign of a tearing component. However, the growth rates scale with a fractional power of the resistivity near the q = 2 surface. The results have a direct bearing on the conventional edge cutoff procedures used in most ideal MHD codes, as well as implications for ITER and for future reactor options.« less

  14. Gyrokinetic simulation of microturbulence in EAST tokamak

    NASA Astrophysics Data System (ADS)

    Xiao, Yong; Zhang, Taige; Zhao, Chen

    2014-10-01

    A complete understanding of anomalous transport is critical for designing future magnetic fusion reactors. It is generally accepted that the micro-scale turbulence leads to anomalous transport. For low beta toroidal plasmas, the electrostatic modes may dominate and ion temperature gradient (ITG) mode and trapped electron mode (TEM) are two very important candidates accounting for ion and electron turbulent transport respectively. Recently the massively parallel gyrokinetic simulation has emerged as a major tool to investigate the nonlinear physics of the turbulent transport. The newly-developed capabilities enable the gyrokinetic code GTC to simulate the turbulent transport for real tokamak plasma shape and profiles. These capabilities include a new gyrokinetic Poisson solver and zonal flow solver suitable for general plasma shape and profiles, improvements on the conventional four-point gyroaverage and newly-developed nonuniform initial marker loading. The GTC code is now able to import experimental plasma profiles and equilibrium magnetic field that come from the EFIT or TRANSP equilibrium reconstruction. Linear and nonlinear gyrokinetic simulations are carried out with the new capabilities in GTC for the electron coherent mode (ECM) recently observed in the EAST tokamak (EAST shot # 38300). We found that in the pedestal region with strong electron temperature gradient, the unstable waves propagate in the electron diamagnetic direction, showing a trapped electron mode (TEM) feature. It is also found in the collisionless limit, the linear mode frequency is higher than that from the experiment.

  15. Predicting temperature and density profiles in tokamaks

    SciTech Connect

    Bateman, G.; Kritz, A.H.; Kinsey, J.E.; Redd, A.J.; Weiland, J.

    1998-05-01

    A fixed combination of theory-based transport models, called the Multi-Mode Model, is used in the BALDUR [C. E. Singer {ital et al.}, Comput. Phys. Commun. {bold 49}, 275 (1988)] transport simulation code to predict the temperature and density profiles in tokamaks. The choice of the Multi-Mode Model has been guided by the philosophy of using the best transport theories available for the various modes of turbulence that dominate in different parts of the plasma. The Multi-Mode model has been found to provide a better match to temperature and density profiles than any of the other theory-based models currently available. A description and partial derivation of the Multi-Mode Model is presented, together with three new examples of simulations of the Tokamak Fusion Test Reactor (TFTR) [K. M. McGuire {ital et al.}, Phys. Plasmas {bold 2}, 2176 (1995)]. The first simulation shows the strong effect of recycling on the ion temperature profile in TFTR supershot simulations. The second simulation explores the effect of a plasma current ramp{emdash}where the plasma energy content changes slowly on the energy confinement time scale. The third simulation shows that the Multi-Mode Model reproduces the experimentally measured profiles when tritium is used as the hydrogenic isotope in L-mode (low confinement mode) plasmas. {copyright} {ital 1998 American Institute of Physics.}

  16. Rotation driven by fast ions in tokamaks

    SciTech Connect

    Thyagaraja, A.; Schwander, F.; McClements, K. G.

    2007-11-15

    Collective fast ion effects on flows in tokamaks are investigated analytically and numerically. A general analysis of noncollisional electrodynamic momentum transfer from fast ions to bulk plasma is presented, with polarization effects and dissipation in the bulk plasma taken into account. The analysis is illustrated using idealized simulations of fast ion orbits and radial electric fields in the Mega-Ampere Spherical Tokamak (MAST) [A. Sykes, R. J. Akers, L. C. Appel et al., Nucl. Fusion 41, 1423 (2001)], the Joint European Torus (JET) [P. H. Rebut et al., Nucl. Fusion 25, 1011 (1985)], and ITER [R. Aymar, P. Barabaschi, and Y. Shimomura, Plasma Phys. Controlled Fusion 44, 519 (2002)]. In the MAST simulation, prompt losses of beam ions injected counter to the plasma current drive up a radial electric field that saturates at a level such that beam ions subsequently injected are confined electrostatically. Although the actual radial electric fields in counterinjected MAST discharges are lower than this, the scenario explored in the simulation would be approached in MAST plasmas with sufficiently low collisionality. The JET simulation, although unrealistic, shows that a similar process could be driven by losses of fusion {alpha}-particles from a burning plasma. Test-particle simulations of {alpha}-particles in ITER suggest that performance-limiting instabilities such as neoclassical tearing modes and resistive wall modes could be affected significantly by flows associated with radial fast particle currents.

  17. Rotation driven by fast ions in tokamaks

    NASA Astrophysics Data System (ADS)

    Thyagaraja, A.; Schwander, F.; McClements, K. G.

    2007-11-01

    Collective fast ion effects on flows in tokamaks are investigated analytically and numerically. A general analysis of noncollisional electrodynamic momentum transfer from fast ions to bulk plasma is presented, with polarization effects and dissipation in the bulk plasma taken into account. The analysis is illustrated using idealized simulations of fast ion orbits and radial electric fields in the Mega-Ampère Spherical Tokamak (MAST) [A. Sykes, R. J. Akers, L. C. Appel et al., Nucl. Fusion 41, 1423 (2001)], the Joint European Torus (JET) [P. H. Rebut et al., Nucl. Fusion 25, 1011 (1985)], and ITER [R. Aymar, P. Barabaschi, and Y. Shimomura, Plasma Phys. Controlled Fusion 44, 519 (2002)]. In the MAST simulation, prompt losses of beam ions injected counter to the plasma current drive up a radial electric field that saturates at a level such that beam ions subsequently injected are confined electrostatically. Although the actual radial electric fields in counterinjected MAST discharges are lower than this, the scenario explored in the simulation would be approached in MAST plasmas with sufficiently low collisionality. The JET simulation, although unrealistic, shows that a similar process could be driven by losses of fusion α-particles from a burning plasma. Test-particle simulations of α-particles in ITER suggest that performance-limiting instabilities such as neoclassical tearing modes and resistive wall modes could be affected significantly by flows associated with radial fast particle currents.

  18. Midplane Faraday rotation: A tokamak densitometer

    NASA Astrophysics Data System (ADS)

    Jobes, F. C.

    1995-01-01

    The density in a tokamak can be determined by measuring the Faraday rotation of a laser directed tangent to the toroidal field. If there is a horizontal array of such beams, then ne(R) can be readily obtained with a simple Abel inversion about the center line of the tokamak. For a large machine, such as ITER, TPX, or JT-60, a 10.6 μm laser would be appropriate. If the machine operated at a full field of 10-50 T m and a peak density of 2.5×1020/m3, the rotation angle would be quite large—about 15°-75° per pass. An elegant measurement system can be made up from a single laser beam diffracted off a moving grating to form a fan of ˜10 probe beams. With the addition of a few optical components to the system, the return beams can be recombined and sent to a single detector. In the detector there is a separate frequency component for both the right and left hand component of each ray. These can be separated electronically to provide a reference and probe signal for each ray; the difference in phase between the two signals is twice the Faraday rotation angle.

  19. System studies for quasi-steady-state advanced physics tokamak

    SciTech Connect

    Reid, R.L.; Peng, Y.K.M.

    1983-11-01

    Parametric studies were conducted using the Fusion Engineering Design Center (FEDC) Tokamak Systems Code to investigate the impact of veriation in physics parameters and technology limits on the performance and cost of a low q/sub psi/, high beta, quasi-steady-state tokamak for the purpose of fusion engineering experimentation. The features and characteristics chosen from each study were embodied into a single Advanced Physics Tokamak design for which a self-consistent set of parameters was generated and a value of capital cost was estimated.

  20. /sup 3/He functions in tokamak-pumped laser systems

    SciTech Connect

    Jassby, D.L.

    1986-10-01

    /sup 3/He placed in an annular cell around a tokamak fusion generator can convert moderated fusion neutrons to energetic ions by the /sup 3/He(n,p)T reaction, and thereby excite gaseous lasants mixed with the /sup 3/He while simultaneously breeding tritium. The total /sup 3/He inventory is about 4 kg for large tokamak devices. Special configurations of toroidal-field magnets, neutron moderators and beryllium reflectors are required to permit nearly uniform neutron current into the laser cell with minimal attenuation. The annular laser radiation can be combined into a single output beam at the top of the tokamak.

  1. Effect of ICRF Heating on Single Particle Confinement in Tokamaks,

    DTIC Science & Technology

    1980-03-01

    80 K W WHANG. 6 .J MORALES N0001IG75C4476 W4CLASSIFlED PP"-73 ML IND 4, LAa4 5 057 Effect of ICRP Heating on Single Particle Confinement in Tokamaks ...bas =akapmwd a b 11 1Af b tmhmdin4 -2- ABSTRACT The simultaneous effect of ion heating and spatial diffusion due to ICRF heating in tokamak geometry... Tokamak confinement devices. Previous theoretical studies I1 2 of this topic have dealt with important questions related to the efficiency of the heating

  2. Nonlinear stabilization of tokamak microturbulence by fast ions.

    PubMed

    Citrin, J; Jenko, F; Mantica, P; Told, D; Bourdelle, C; Garcia, J; Haverkort, J W; Hogeweij, G M D; Johnson, T; Pueschel, M J

    2013-10-11

    Nonlinear electromagnetic stabilization by suprathermal pressure gradients found in specific regimes is shown to be a key factor in reducing tokamak microturbulence, augmenting significantly the thermal pressure electromagnetic stabilization. Based on nonlinear gyrokinetic simulations investigating a set of ion heat transport experiments on the JET tokamak, described by Mantica et al. [Phys. Rev. Lett. 107, 135004 (2011)], this result explains the experimentally observed ion heat flux and stiffness reduction. These findings are expected to improve the extrapolation of advanced tokamak scenarios to reactor relevant regimes.

  3. ECH by FEL and gyrotron sources on the Microwave Tokamak Experiment (MTX) tokamak

    SciTech Connect

    Stallard, B.W.; Turner, W.C.; Allen, S.L.; Byers, J.A.; Felker, B.; Fenstermacher, M.E.; Ferguson, S.W.; Hooper, E.G.; Thomassen, K.I.; Throop, A.L. ); Makowski, M.A. )

    1990-08-09

    The Microwave Tokamak Experiment (MTX) at LLNL is studying the physics of intense pulse ECH is a high-density tokamak plasma using a microwave FEL. Related technology development includes the FEL, a windowless quasi-optical transmission system, and other microwave components. Initial plasma experiments have been carried out at 140 GHz with single rf pulses generated using the ETA-II accelerator and the ELF wiggler. Peak power levels up to 0.2 GW and pulse durations up to 10 ns were achieved for injection into the plasma using as untapered wiggler. FEL pulses were transmitted over 33 m from the FEL to MTX using six mirrors mounted in a 50-cm-diam evacuated pipe. Measurements of the microwave beam and transmission through the plasma were carried out. For future rapid pulse experiments at high average power (4 GW peak power, 5kHz pulse rate, and {bar P} > 0.5 MW) using the IMP wiggler with tapered magnetic field, a gyrotron (140 GHz, 400 kW cw or up to 1 MW short pulse) is being installed to drive the FEL input or to directly heat the tokamak plasma at full gyrotron power. Quasi-optic techniques will be used to couple the gyrotron power. For direct plasma heating, the gyrotron will couple into the existing mirror transport system. Using both sources of rf generation, experiments are planned to investigate intense pulse absorption and tokamak physics, such as the ECH of a pellet-fueled plasma and plasma control using localized heating. 12 refs., 9 figs.

  4. ECH by FEL and gyrotron sources on the Microwave Tokamak Experiment (MTX) tokamak

    NASA Astrophysics Data System (ADS)

    Stallard, B. W.; Turner, W. C.; Allen, S. L.; Byers, J. A.; Felker, B.; Fenstermacher, M. E.; Ferguson, S. W.; Hooper, E. G.; Thomassen, K. I.; Throop, A. L.

    1990-08-01

    The Microwave Tokamak Experiment (MTX) at LLNL is studying the physics of intense pulse ECH is a high-density tokamak plasma using a microwave FEL. Related technology development includes the FEL, a windowless quasi-optical transmission system, and other microwave components. Initial plasma experiments have been carried out at 140 GHz with single RF pulses generated using the ETA-2 accelerator and the ELF wiggler. Peak power levels up to 0.2 GW and pulse durations up to 10 ns were achieved for injection into the plasma using as untapered wiggler. FEL pulses were transmitted over 33 m from the FEL to MTX using six mirrors mounted in a 50 cm diam evacuated pipe. Measurements of the microwave beam and transmission through the plasma were carried out. For future rapid pulse experiments at high average power (4 GW peak power, 5 kHz pulse rate, and bar P is greater than 0.5 MW) using the IMP wiggler with tapered magnetic field, a gyrotron (140 GHz, 400 kW CW or up to 1 MW short pulse) is being installed to drive the FEL input or to directly heat the tokamak plasma at full gyrotron power. Quasi-optic techniques will be used to couple the gyrotron power. For direct plasma heating, the gyrotron will couple into the existing mirror transport system. Using both sources of RF generation, experiments are planned to investigate intense pulse absorption and tokamak physics, such as the ECH of a pellet-fueled plasma and plasma control using localized heating.

  5. TFTR/JET INTOR workshop on plasma transport tokamaks

    SciTech Connect

    Singer, C.E.

    1985-01-01

    This report summarizes the proceedings of a Workshop on transport models for prediction and analysis of tokamak plasma confinement. Summaries of papers on theory, predictive modeling, and data analysis are included.

  6. On Stochastic Control of Tokamak and Artificial Intelligence

    NASA Astrophysics Data System (ADS)

    Rastovic, Danilo

    2007-12-01

    Instead of the theory of invariant manifolds and entropy reduction, the theory of fractional Brownian motions and artificiall neural networks is used for description of advanced methods for control of tokamak plasma behaviour.

  7. Tokamak reactor cost model based on STARFIRE/WILDCAT costing

    SciTech Connect

    Evans, K. Jr.

    1983-03-01

    A cost model is presented which is useful for survey and comparative studies of tokamak reactors. The model is heavily based on STARFIRE and WILDCAT costing guidelines, philosophies, and procedures and reproduces the costing for these devices quite accurately.

  8. Improvement of tokamak performance by injection of electrons

    SciTech Connect

    Ono, Masayuki

    1992-12-01

    Concepts for improving tokamak performance by utilizing injection of hot electrons are discussed. Motivation of this paper is to introduce the research work being performed in this area and to refer the interested readers to the literature for more detail. The electron injection based concepts presented here have been developed in the CDX, CCT, and CDX-U tokamak facilities. The following three promising application areas of electron injection are described here: 1. Non-inductive current drive, 2. Plasma preionization for tokamak start-up assist, and 3. Charging-up of tokamak flux surfaces for improved plasma confinement. The main motivation for the dc-helicity injection current drive is in its efficiency that, in theory, is independent of plasma density. This property makes it attractive for driving currents in high density reactor plasmas.

  9. Diagnosing transient plasma status: from solar atmosphere to tokamak divertor

    NASA Astrophysics Data System (ADS)

    Giunta, A. S.; Henderson, S.; O'Mullane, M.; Harrison, J.; Doyle, J. G.; Summers, H. P.

    2016-09-01

    This work strongly exploits the interdisciplinary links between astrophysical (such as the solar upper atmosphere) and laboratory plasmas (such as tokamak devices) by sharing the development of a common modelling for time-dependent ionisation. This is applied to the interpretation of solar flare data observed by the UVSP (Ultraviolet Spectrometer and Polarimeter), on-board the Solar Maximum Mission and the IRIS (Interface Region Imaging Spectrograph), and also to data from B2-SOLPS (Scrape Off Layer Plasma Simulations) for MAST (Mega Ampère Spherical Tokamak) Super-X divertor upgrade. The derived atomic data, calculated in the framework of the ADAS (Atomic Data and Analysis Structure) project, allow equivalent prediction in non-stationary transport regimes and transients of both the solar atmosphere and tokamak divertors, except that the tokamak evolution is about one thousand times faster.

  10. Cash boost for UK’s MAST tokamak

    NASA Astrophysics Data System (ADS)

    2017-06-01

    The Mega Amp Spherical Tokamak (MAST) at the Culham Centre for Fusion Energy in Oxfordshire, UK, has received £21m for a series of upgrades to study the best way to extract waste fuel from the plasma it contains.

  11. An emerging understanding of H-mode discharges in tokamaks

    SciTech Connect

    Groebner, R.J.

    1992-12-01

    A remarkable degree of consistency of experimental results from tokamaks throughout the world has developed with regard to the phenomenology of the transition from L-mode to H-mode confinement in tokamaks. The transition is initiated in a narrow layer at the plasma periphery where density fluctuations are suppressed and steep gradients of temperature and density form in a region with large first and second radial derivatives in the [upsilon][sub E][sup [yields

  12. Experimental observations and modelling of intrinsic rotation reversals in tokamaks

    NASA Astrophysics Data System (ADS)

    Camenen, Y.; Angioni, C.; Bortolon, A.; Duval, B. P.; Fable, E.; Hornsby, W. A.; McDermott, R. M.; Na, D. H.; Na, Y.-S.; Peeters, A. G.; Rice, J. E.

    2017-03-01

    The progress made in understanding spontaneous toroidal rotation reversals in tokamaks is reviewed and current ideas to solve this ten-year-old puzzle are explored. The paper includes a summarial synthesis of the experimental observations in AUG, C-Mod, KSTAR, MAST and TCV tokamaks, reasons why turbulent momentum transport is thought to be responsible for the reversals, a review of the theory of turbulent momentum transport and suggestions for future investigations.

  13. Design of a microwave calorimeter for the microwave tokamak experiment

    SciTech Connect

    Marinak, M. )

    1988-10-07

    The initial design of a microwave calorimeter for the Microwave Tokamak Experiment is presented. The design is optimized to measure the refraction and absorption of millimeter rf microwaves as they traverse the toroidal plasma of the Alcator C tokamak. Techniques utilized can be adapted for use in measuring high intensity pulsed output from a microwave device in an environment of ultra high vacuum, intense fields of ionizing and non-ionizing radiation and intense magnetic fields. 16 refs.

  14. Fast tomographic methods for the tokamak ISTTOK

    NASA Astrophysics Data System (ADS)

    Carvalho, P. J.; Thomsen, H.; Gori, S.; Toussaint, U. v.; Weller, A.; Coelho, R.; Neto, A.; Pereira, T.; Silva, C.; Fernandes, H.

    2008-04-01

    The achievement of long duration, alternating current discharges on the tokamak IST-TOK requires a real-time plasma position control system. The plasma position determination based on magnetic probes system has been found to be inadequate during the current inversion due to the reduced plasma current. A tomography diagnostic has been therefore installed to supply the required feedback to the control system. Several tomographic methods are available for soft X-ray or bolo-metric tomography, among which the Cormack and Neural networks methods stand out due to their inherent speed of up to 1000 reconstructions per second, with currently available technology. This paper discusses the application of these algorithms on fusion devices while comparing performance and reliability of the results. It has been found that although the Cormack based inversion proved to be faster, the neural networks reconstruction has fewer artifacts and is more accurate.

  15. Tearing mode analysis in tokamaks, revisited

    SciTech Connect

    Nishimura, Y.; Callen, J.D.; Hegna, C.C.

    1998-12-01

    A new {Delta}{sup {prime}} shooting code has been developed to investigate tokamak plasma tearing mode stability in a cylinder and large aspect ratio ({epsilon}{le}0.25) toroidal geometries, neglecting toroidal mode coupling. A different computational algorithm is used (shooting out from the singular surface instead of into it) to resolve the strong singularities at the mode rational surface, particularly in the presence of the finite pressure term. Numerical results compare favorably with Furth {ital et al.} [H. P. Furth {ital et al.}, Phys. Fluids {bold 16}, 1054 (1973)] results. The effects of finite pressure, which are shown to decrease {Delta}{sup {prime}}, are discussed. It is shown that the distortion of the flux surfaces by the Shafranov shift, which modifies the geometry metric elements, stabilizes the tearing mode significantly, even in a low-{beta} regime before the toroidal magnetic curvature effects come into play. {copyright} {ital 1998 American Institute of Physics.}

  16. Decommissioning of the Tokamak Fusion Test Reactor

    SciTech Connect

    E. Perry; J. Chrzanowski; C. Gentile; R. Parsells; K. Rule; R. Strykowsky; M. Viola

    2003-10-28

    The Tokamak Fusion Test Reactor (TFTR) at the Princeton Plasma Physics Laboratory was operated from 1982 until 1997. The last several years included operations with mixtures of deuterium and tritium. In September 2002, the three year Decontamination and Decommissioning (D&D) Project for TFTR was successfully completed. The need to deal with tritium contamination as well as activated materials led to the adaptation of many techniques from the maintenance work during TFTR operations to the D&D effort. In addition, techniques from the decommissioning of fission reactors were adapted to the D&D of TFTR and several new technologies, most notably the development of a diamond wire cutting process for complex metal structures, were developed. These techniques, along with a project management system that closely linked the field crews to the engineering staff who developed the techniques and procedures via a Work Control Center, resulted in a project that was completed safely, on time, and well below budget.

  17. Cooldown of the Compact Ignition Tokamak

    SciTech Connect

    Keeton, D.C.

    1987-08-01

    Cooldown of the Compact Ignition Tokamak (CIT) with the baseline liquid nitrogen cooling system was analyzed. On the basis of this analysis and present knowledge of the two-phase heat transfer, the current baseline CIT can be cooled down in about 1.5 h. An extensive heat transfer test program is recommended to reduce uncertainty in the heat transfer performance and to explore methods for minimizing the cooldown time. An alternate CIT cooldown system is described which uses a pressurized gaseous helium coolant in a closed-loop system. It is shown analytically that this system will cool down the CIT well within 1 h. Confidence in this analysis is sufficiently high that a heat transfer test program would not be necessary. The added cost of this alternate system is estimated to be about $5.3 million. This helium cooling system represents a reasonable backup approach to liquid nitrogen cooling of the CIT. 3 refs., 12 figs., 3 tabs.

  18. Diagnostics modules for tokamak disruption experiments

    SciTech Connect

    Nahm, M.L.; Buchanan, C.D.; Bourham, M.A.; Gilligan, J.G.

    1994-11-01

    Diagnostic modules equipped with various sensors can provide useful information on key parameters for disruption events, e.g. energy deposition, vapor shielding effect, plasma pressure and force distribution. The modules are, basically, DIMES samples (Divertor Materials Evaluation System) equipped with sensors, coupled to digitizing units and interfaced to a data acquisition system. The DIMES samples are part of the lower diverter diagnostics on the DIII-D tokamak. Three top-cap prototype diagnostics modules have been designed and fabricated. The initial testing and calibration have been performed using the SIRENS plasma gun at an energy deposition of 1 to 12 MJ/m{sup 2} over 0.1 to 1.0 ms, with a plasma pressure >100 MPa.

  19. Passive runaway electron suppression in tokamak disruptions

    SciTech Connect

    Smith, H. M.; Helander, P.

    2013-07-15

    Runaway electrons created in disruptions pose a serious problem for tokamaks with large current. It would be desirable to have a runaway electron suppression method which is passive, i.e., a method that does not rely on an uncertain disruption prediction system. One option is to let the large electric field inherent in the disruption drive helical currents in the wall. This would create ergodic regions in the plasma and increase the runaway losses. Whether these regions appear at a suitable time and place to affect the formation of the runaway beam depends on disruption parameters, such as electron temperature and density. We find that it is difficult to ergodize the central plasma before a beam of runaway current has formed. However, the ergodic outer region will make the Ohmic current profile contract, which can lead to instabilities that yield large runaway electron losses.

  20. Argonne Plasma Engineering Experiment (APEX) Tokamak

    SciTech Connect

    Norem, J.H.; Balka, L.J.; Kulovitz, E.E.; Magill, S.R.; McGhee, D.G.; Moretti, A.; Praeg, W.F.

    1981-03-01

    The Argonne Plasma Engineering Experiment (APEX) Tokamak was designed to provide hot plasmas for reactor-relevant experiments with rf heating (current drive) and plasma wall experiments, principally in-situ low-Z wall coating and maintenance. The device, sized to produce energetic plasmas at minimum cost, is small (R = 51 cm, r = 15 cm) but capable of high currents (100 kA) and long pulse durations (100 ms). A design using an iron central core with no return legs, pure tension tapewound toroidal field coils, digital radial position control, and UHV vacuum technology was used. Diagnostics include monochrometers, x-ray detectors, and a microwave interferometer and radiometer for density and temperature measurements. Stable 100 ms shots were produced with electron temperatures in the range 500 to 1000 eV. Initial results included studies of thermal desorption and recoating of wall materials.

  1. Tokamak Simulation Code modeling of NSTX

    SciTech Connect

    S.C. Jardin; S. Kaye; J. Menard; C. Kessel; A.H. Glasser

    2000-07-20

    The Tokamak Simulation Code [TSC] is widely used for the design of new axisymmetric toroidal experiments. In particular, TSC was used extensively in the design of the National Spherical Torus eXperiment [NSTX]. The authors have now benchmarked TSC with initial NSTX results and find excellent agreement for plasma and vessel currents and magnetic flux loops when the experimental coil currents are used in the simulations. TSC has also been coupled with a ballooning stability code and with DCON to provide stability predictions for NSTX operation. TSC has also been used to model initial CHI experiments where a large poloidal voltage is applied to the NSTX vacuum vessel, causing a force-free current to appear in the plasma. This is a phenomenon that is similar to the plasma halo current that sometimes develops during a plasma disruption.

  2. Toroidal microinstability studies of high temperature tokamaks

    SciTech Connect

    Rewoldt, G.; Tang, W.M.

    1989-07-01

    Results from comprehensive kinetic microinstability calculations are presented showing the effects of toroidicity on the ion temperature gradient mode and its relationship to the trapped-electron mode in high-temperature tokamak plasmas. The corresponding particle and energy fluxes have also been computed. It is found that, although drift-type microinstabilities persist over a wide range of values of the ion temperature gradient parameter /eta//sub i/ /equivalent to/ (dlnT/sub i//dr)/(dlnn/sub i//dr), the characteristic features of the dominant mode are those of the /eta//sub i/-type instability when /eta//sub i/ > /eta//sub ic/ /approximately/1.2 to 1.4 and of the trapped-electron mode when /eta//sub i/ < /eta//sub ic/. 16 refs., 7 figs.

  3. Control of Asymmetric Magnetic Perturbations in Tokamaks

    SciTech Connect

    Park, Jong-kyu; Schaffer, Michael J.; Menard, Jonathan E.; Boozer, Allen H.

    2007-10-03

    The sensitivity of tokamak plasmas to very small deviations from the axisymmetry of the magnetic field |δ→(over)Β/→(over)Β|≈ 10–4 is well known. What was not understood until very recently is the importance of the perturbation to the plasma equilibrium in assessing the effects of externally produced asymmetries in the magnetic field, even far from a stability limit. DIII-D and NSTX experiments find that when the deleterious effects of asymmetries are mitigated, the external asymmetric field was often made stronger and with an increased interaction with the magnetic field of the unperturbed equilibrium fields. This paper explains these counter intuitive results. The explanation using ideal perturbed equilibria has important implications for the control of field errors in all toroidal plasmas.

  4. Nusselt number scaling in tokamak plasma turbulence

    SciTech Connect

    Takeda, K.; Benkadda, S.; Hamaguchi, S.; Wakatani, M.

    2005-05-15

    Anomalous heat transport caused by ion temperature gradient (ITG) driven turbulence in tokamak plasmas is evaluated from numerical simulations of the two-dimensional (2D) partial-differential equations of the ITG model and of a reduced 1D version derived from a quasilinear approximation. In the strongly turbulent state, intermittent bursts of thermal transport are observed in both cases. In the strongly turbulent regime, the reduced model as well as the direct numerical simulation show that the Nusselt number Nu (normalized heat flux) scales with the normalized ion pressure gradient K{sub i} as Nu{proportional_to}K{sub i}{sup 1/3}. Since the Rayleigh number for ITG turbulence is proportional to K{sub i}, the Nusselt number scaling for ITG turbulence is thus similar to the classical thermal transport scaling for Rayleigh-Benard convections in neutral fluids.

  5. Control of asymmetric magnetic perturbations in tokamaks.

    PubMed

    Park, Jong-Kyu; Schaffer, Michael J; Menard, Jonathan E; Boozer, Allen H

    2007-11-09

    The sensitivity of tokamak plasmas to very small deviations from the axisymmetry of the magnetic field |deltaB/B| approximately 10{-4} is well known. What was not understood until very recently is the importance of the perturbation to the plasma equilibrium in assessing the effects of externally produced asymmetries in the magnetic field, even far from a stability limit. DIII-D and NSTX experiments find that when the deleterious effects of asymmetries are mitigated, the external asymmetric field was often made stronger and had an increased interaction with the magnetic field of the unperturbed equilibrium. This Letter explains these counterintuitive results. The explanation using ideal perturbed equilibria has important implications for the control of field errors in all toroidal plasmas.

  6. Transport bifurcation in a rotating tokamak plasma.

    PubMed

    Highcock, E G; Barnes, M; Schekochihin, A A; Parra, F I; Roach, C M; Cowley, S C

    2010-11-19

    The effect of flow shear on turbulent transport in tokamaks is studied numerically in the experimentally relevant limit of zero magnetic shear. It is found that the plasma is linearly stable for all nonzero flow shear values, but that subcritical turbulence can be sustained nonlinearly at a wide range of temperature gradients. Flow shear increases the nonlinear temperature gradient threshold for turbulence but also increases the sensitivity of the heat flux to changes in the temperature gradient, except over a small range near the threshold where the sensitivity is decreased. A bifurcation in the equilibrium gradients is found: for a given input of heat, it is possible, by varying the applied torque, to trigger a transition to significantly higher temperature and flow gradients.

  7. Fast tomographic methods for the tokamak ISTTOK

    SciTech Connect

    Carvalho, P. J.; Coelho, R.; Neto, A.; Pereira, T.; Silva, C.; Fernandes, H.; Gori, S.; Toussaint, U. v.

    2008-04-07

    The achievement of long duration, alternating current discharges on the tokamak IST-TOK requires a real-time plasma position control system. The plasma position determination based on magnetic probes system has been found to be inadequate during the current inversion due to the reduced plasma current. A tomography diagnostic has been therefore installed to supply the required feedback to the control system. Several tomographic methods are available for soft X-ray or bolo-metric tomography, among which the Cormack and Neural networks methods stand out due to their inherent speed of up to 1000 reconstructions per second, with currently available technology. This paper discusses the application of these algorithms on fusion devices while comparing performance and reliability of the results. It has been found that although the Cormack based inversion proved to be faster, the neural networks reconstruction has fewer artifacts and is more accurate.

  8. Anisotropic pressure tokamak equilibrium and stability considerations

    SciTech Connect

    Salberta, E.R.; Grimm, R.C.; Johnson, J.L.; Manickam, J.; Tang, W.M.

    1987-02-01

    Investigation of the effect of pressure anisotropy on tokamak equilibrium and stability is made with an MHD model. Realistic perpendicular and parallel pressure distributions, P/sub perpendicular/(psi,B) and P/sub parallel/(psi,B), are obtained by solving a one-dimensional Fokker-Planck equation for neutral beam injection to find a distribution function f(E, v/sub parallel//v) at the position of minimum field on each magnetic surface and then using invariance of the magnetic moment to determine its value at each point on the surface. The shift of the surfaces of constant perpendicular and parallel pressure from the flux surfaces depends strongly on the angle of injection. This shift explains the observed increase or decrease in the stability conditions. Estimates of the stabilizing effect of hot trapped ions indicates that a large fraction must be nonresonant and thus decoupled from the bad curvature before it becomes important.

  9. Equilibrium properties on the EAST superconducting tokamak

    NASA Astrophysics Data System (ADS)

    Qian, J. P.; Wan, B. N.; Lao, L. L.; Shen, B.; Sabbagh, S. A.; Menard, J.; Sun, Y. W.; Duan, Y. M.; Li, J. H.; Xiao, B. J.; Gong, X. Z.; Gong

    2009-06-01

    The Experimental Advanced Superconducting Tokamak (EAST) has a major radius of R0 = 1.75 m and a midplane halfwidth of 0.5 m. It has been operated with a toroidal magnetic field B0 = 2 T and Ip ≤ 500 kA. The evolution of the plasma equilibrium is analysed between discharges by Equilibrium Fitting Code (EFIT). Limiter, single-null and double-null diverted configurations have been produced. A plasma elongation in the range 1.3 ≤ κ ≤ 1.9 and a triangularity in the range 0.1 ≤ δ ≤ 0.55 have been sustained. The operation space of elongated discharges is also presented based on the EAST database.

  10. Neutral Beam Injection in the Electric Tokamak

    NASA Astrophysics Data System (ADS)

    Gourdain, P.-A.; Carter, T. A.; Gauvreau, J.-L.; Grossman, A.; Lafonteese, D. J.; Pace, D. C.; Schmitz, L. W.; Taylor, R. J.; White, A. E.; Yates, T. F.

    2004-11-01

    The Electric Tokamak (ET) at UCLA (Bt=0.25T, R=5m, a=1m, Te(0)=300eV, tau(0)=1s) is now running long shots (5s). A new development program was started last year to include a neutral beam in the daily operations of the machine. As a result, a 10kV neutral beam injector was built to deal with plasma and measurement issues. The design and parameters of the beam are discussed. The source is based on an RF generated plasma, with a single extraction grid providing an accel-decel configuration. Plasma neutralization efficiency is also presented. Co- or counter injection is now possible using a single beam. The construction of a second beam is planned for simultaneous co- and counter injections for toroidal momentum input control. Plasma toroidal and poloidal rotation, particle diffusion and current drive effects will be presented.

  11. Instrumentation and controls of an ignited tokamak

    SciTech Connect

    Becraft, W.R.; Golzy, J.; Houlberg, W.A.; Kukielka, C.A.; Onega R.J.; Raju, G.V.S.; Stone, R.S.

    1980-10-01

    The instrumentation and controls (I and C) of an ignited plasma magnetically confined in a tokamak configuration needs increased emphasis in the following areas: (1) physics implications for control; (2) plasma shaping/position control; and (3) control to prevent disruptive instabilities. This document reports on the FY 1979 efforts in these and other areas. Also presented are discusssions in the areas of: (1) diagnostics suitable for the Engineering Test Facility (ETF); and (2) future research and development (R and D) needs. The appendices focus attention on some preliminary ideas about the measurement of the deuteron-triton (D-T) ratio in the plasma, synchrotron radiation, and divertor control. Finally, an appendix documenting the thermal consequences to the first wall of a MPD is presented.

  12. Plasma rotation in the PDX tokamak

    SciTech Connect

    Brau, K.; Bitter, M.; Goldston, R.J.; Manos, D.; McGuire, K.; Suckewer, S.

    1983-06-01

    Toroidal and poloidal rotation has been measured in the Poloidal Divertor Experiment (PDX) tokamak in ohmic- and neutral-beam-heated plasmas in a variety of discharge conditions and in both circular and diverted configurations. Rotation velocities were deduced from Doppler shifts of magnetic dipole (M1) lines and lines of optically allowed transitions in the visible and uv regions, from K/sub ..cap alpha../ emission, and also from an array of magnetic pickup loops. Poloidal and toroidal rotation velocities in ohmically heated discharges were unusually less than 3 x 10/sup 5/ cm/sec. Near the plasma edge the toroidal-rotation velocity varies with poloidal angle both before and during neutral-beam injection. No systematic poloidal rotation was observed during neutral-beam injection centered about or displaced 10 cm from the horizontal midplane, which implies that the poloidal damping time tau/sub theta/ < 0.5 tau/sub ii/, consistent with theoretical estimates.

  13. A lithium deposition system for tokamak devices*

    NASA Astrophysics Data System (ADS)

    Graziul, Christopher; Majeski, Richard; Kaita, Robert; Hoffman, Daniel; Timberlake, John; Card, David

    2002-11-01

    The production of a lithium deposition system using commercially available components is discussed. This system is intended to provide a fresh lithium wall coating between discharges in a tokamak. For this purpose, a film 100-200 Å thick is sufficient to ensure that the plasma interacts solely with the lithium. A test system consisting of a lithium evaporator and a deposition monitor has been designed and constructed to investigate deposition rates and coverage. A Thermionics 3kW e-gun is used to rapidly evaporate small amounts of solid lithium. An Inficon XTM/2 quartz deposition monitor then measures deposition rate at varying distances, positions and angles relative to the e-gun crucible. Initial results from the test system will be presented. *Supported by US DOE contract #DE-AC02-76CH-03073

  14. Status of ECRH project on EAST Tokamak

    SciTech Connect

    Wang, Xiaojie; Liu, Fukun; Shan, Jiafang; Xu, Handong; Wu, Dajun; Li, Bo; Zhang, Jiang; Huang, Yiyun; Tang, Yunying; Xu, Weiye; Hu, Huaichuan; Wang, Jian; Xu, Li; Wei, Wei

    2014-02-12

    A 140GHz electron cyclotron resonance heating and current drive (EC H and CD) project for EAST Tokamak is launched in 2011 with a total power of 4MW and pulse length of 100 s. The main objectives of the system are to provide central H and CD, assist start-up and control of MHD activities. The system comprises four gyrotrons each with nominal output power of 1MW at 140GHz. The RF power, transmitted through four evacuated corrugated waveguides will be injected into plasma from the low field side (radial port). The front steering equatorial launcher directs the RF beam over ±25° toroidally and scans over 38° poloidally. At present, the construction of the first 1MW system is undergoing for the expected campaign in the end of 2013. In this paper, the current status of the development and the design of the 140-GHz ECRH system are presented.

  15. TRAIL: a tokamak rail gun limiter

    SciTech Connect

    Yu, W.S.; Powell, J.R.; Usher, J.L.

    1980-01-01

    An attractive new limiter concept is investigated. The TRAIL (Tokamak Rail Gun Limiter) system impacts a stream of moderate velocity pellets (100 to 200 m/sec through the plasma edge region to absorb energy and define the plasma boundary. The pellets are recycled, after cooling, to the injector in an E-M mass accelerator. Heat fluxes of approx. 30,000 W/cm/sup 2/ can be readily accommodated by the pellets, with very low recirculating power requirements (approx. 0.1%) for the accelerator. The mass accelerator velocity requirements are well within the present state-of-the-art (several km/sec). Accelerators injecting pellets at approx. 1 km/sec can be used to control local plasma temperature and current profiles and to act as energy absorbers to shut down the plasma without damage to the first wall if a plasma disruption occurs.

  16. Tokamak current driven by poloidally asymmetric fueling

    SciTech Connect

    Helander, P.; Fueloep, T.; Lisak, M.

    2006-10-15

    It is shown that poloidally asymmetric particle transport or fueling in a tokamak generally produces an electric current parallel to the magnetic field, in particular if the transport or fueling is up-down asymmetric. For instance, a current arises in the edge region if most particle transport across the last closed flux surface occurs in the midplane while most refueling comes from recycling near the X-point. This current is negative relative to the bulk plasma current (and thus stabilizing to peeling modes) if the ion drift is toward the X-point, and changes direction if the magnetic field is reversed. However, this current appears to be smaller than the pedestal bootstrap current under typical conditions.

  17. Transport Bifurcation in a Rotating Tokamak Plasma

    SciTech Connect

    Highcock, E. G.; Barnes, M.; Schekochihin, A. A.; Parra, F. I.; Roach, C. M.; Cowley, S. C.

    2010-11-19

    The effect of flow shear on turbulent transport in tokamaks is studied numerically in the experimentally relevant limit of zero magnetic shear. It is found that the plasma is linearly stable for all nonzero flow shear values, but that subcritical turbulence can be sustained nonlinearly at a wide range of temperature gradients. Flow shear increases the nonlinear temperature gradient threshold for turbulence but also increases the sensitivity of the heat flux to changes in the temperature gradient, except over a small range near the threshold where the sensitivity is decreased. A bifurcation in the equilibrium gradients is found: for a given input of heat, it is possible, by varying the applied torque, to trigger a transition to significantly higher temperature and flow gradients.

  18. Vertically stabilized elongated cross-section tokamak

    DOEpatents

    Sheffield, George V.

    1977-01-01

    This invention provides a vertically stabilized, non-circular (minor) cross-section, toroidal plasma column characterized by an external separatrix. To this end, a specific poloidal coil means is added outside a toroidal plasma column containing an endless plasma current in a tokamak to produce a rectangular cross-section plasma column along the equilibrium axis of the plasma column. By elongating the spacing between the poloidal coil means the plasma cross-section is vertically elongated, while maintaining vertical stability, efficiently to increase the poloidal flux in linear proportion to the plasma cross-section height to achieve a much greater plasma volume than could be achieved with the heretofore known round cross-section plasma columns. Also, vertical stability is enhanced over an elliptical cross-section plasma column, and poloidal magnetic divertors are achieved.

  19. Gas Fuelling System for SST-1Tokamak

    NASA Astrophysics Data System (ADS)

    Dhanani, Kalpesh; Raval, D. C.; Khan, Ziauddin; Semwal, Pratibha; George, Siju; Paravastu, Yuvakiran; Thankey, Prashant; Khan, M. S.; Pradhan, Subrata

    2017-04-01

    SST-1 Tokamak, the first Indian Steady-state Superconducting experimental device is at present under operation in the Institute for Plasma Research. For plasma break down & initiation, piezoelectric valve based gas feed system is implemented as a primary requirement due to its precise control, easy handling, low construction and maintenance cost and its flexibility in the selection of the working gas. Hydrogen gas feeding with piezoelectric valve is used in the SST-1 plasma experiments. The piezoelectric valves used in SST-1 are remotely driven by a PXI based platform and are calibrated before each SST-1 plasma operation with precise control. This paper will present the technical development and the results of the gas fuelling system of SST-1.

  20. Nonlinear lower hybrid modeling in tokamak plasmas

    SciTech Connect

    Napoli, F.; Schettini, G.; Castaldo, C.; Cesario, R.

    2014-02-12

    We present here new results concerning the nonlinear mechanism underlying the observed spectral broadening produced by parametric instabilities occurring at the edge of tokamak plasmas in present day LHCD (lower hybrid current drive) experiments. Low frequency (LF) ion-sound evanescent modes (quasi-modes) are the main parametric decay channel which drives a nonlinear mode coupling of lower hybrid (LH) waves. The spectrum of the LF fluctuations is calculated here considering the beating of the launched LH wave at the radiofrequency (RF) operating line frequency (pump wave) with the noisy background of the RF power generator. This spectrum is calculated in the frame of the kinetic theory, following a perturbative approach. Numerical solutions of the nonlinear LH wave equation show the evolution of the nonlinear mode coupling in condition of a finite depletion of the pump power. The role of the presence of heavy ions in a Deuterium plasma in mitigating the nonlinear effects is analyzed.

  1. Resistive edge mode instability in stellarator and tokamak geometries

    SciTech Connect

    Mahmood, M. Ansar; Rafiq, T.; Persson, M.; Weiland, J.

    2008-09-15

    Geometrical effects on linear stability of electrostatic resistive edge modes are investigated in the three-dimensional Wendelstein 7-X stellarator [G. Grieger et al., Plasma Physics and Controlled Nuclear Fusion Research 1990 (International Atomic Energy Agency, Vienna, 1991), Vol. 3, p. 525] and the International Thermonuclear Experimental Reactor [Progress in the ITER Physics Basis, Nucl. Fusion 7, S1, S285 (2007)]-like equilibria. An advanced fluid model is used for the ions together with the reduced Braghinskii equations for the electrons. Using the ballooning mode representation, the drift wave problem is set as an eigenvalue equation along a field line and is solved numerically using a standard shooting technique. A significantly larger magnetic shear and a less unfavorable normal curvature in the tokamak equilibrium are found to give a stronger finite-Larmor radius stabilization and a more narrow mode spectrum than in the stellarator. The effect of negative global magnetic shear in the tokamak is found to be stabilizing. The growth rate on a tokamak magnetic flux surface is found to be comparable to that on a stellarator surface with the same global magnetic shear but the eigenfunction in the tokamak is broader than in the stellarator due to the presence of large negative local magnetic shear (LMS) on the tokamak surface. A large absolute value of the LMS in a region of unfavorable normal curvature is found to be stabilizing in the stellarator, while in the tokamak case, negative LMS is found to be stabilizing and positive LMS destabilizing.

  2. Resistive edge mode instability in stellarator and tokamak geometries

    NASA Astrophysics Data System (ADS)

    Mahmood, M. Ansar; Rafiq, T.; Persson, M.; Weiland, J.

    2008-09-01

    Geometrical effects on linear stability of electrostatic resistive edge modes are investigated in the three-dimensional Wendelstein 7-X stellarator [G. Grieger et al., Plasma Physics and Controlled Nuclear Fusion Research 1990 (International Atomic Energy Agency, Vienna, 1991), Vol. 3, p. 525] and the International Thermonuclear Experimental Reactor [Progress in the ITER Physics Basis, Nucl. Fusion 7, S1, S285 (2007)]-like equilibria. An advanced fluid model is used for the ions together with the reduced Braghinskii equations for the electrons. Using the ballooning mode representation, the drift wave problem is set as an eigenvalue equation along a field line and is solved numerically using a standard shooting technique. A significantly larger magnetic shear and a less unfavorable normal curvature in the tokamak equilibrium are found to give a stronger finite-Larmor radius stabilization and a more narrow mode spectrum than in the stellarator. The effect of negative global magnetic shear in the tokamak is found to be stabilizing. The growth rate on a tokamak magnetic flux surface is found to be comparable to that on a stellarator surface with the same global magnetic shear but the eigenfunction in the tokamak is broader than in the stellarator due to the presence of large negative local magnetic shear (LMS) on the tokamak surface. A large absolute value of the LMS in a region of unfavorable normal curvature is found to be stabilizing in the stellarator, while in the tokamak case, negative LMS is found to be stabilizing and positive LMS destabilizing.

  3. A programmatic framework for the Tokamak Physics Experiment (TPX)

    SciTech Connect

    Thomassen, K.I. ); Goldston, R.J. ); Neilson, G.H. )

    1993-09-01

    Significant advances have been made in the confinement of reactor-grade plasmas, so that the authors are now preparing for experiments at the [open quotes]power breakeven[close quotes] level in the JET and TFTR experiments. In ITER the authors will extend the performance of tokamaks into the burning plasma regime, develop the technology of fusion reactors, and produce over a gigawatt of fusion power. Besides taking these crucial steps toward the technical feasibility of fusion, the authors must also take steps to ensure its economic acceptability. The broad requirements for economically attractive tokamak reactors based on physics advancements have been set forth in a number of studies. An advanced physics data base is emerging from a physics program of concept improvement using existing tokamaks around the world. This concept improvements program is emerging as the primary focus of the US domestic tokamak program, and a key element of that program is the proposed Tokamak Physics Experiment (TPX). With TPX the authors can develop the scientific data base for compact, continuously-operating fusion reactors, using advanced steady-state control techniques to improve plasma performance. The authors can develop operating techniques needed to ensure the success of ITER and provide first-time experience with several key fusion reactor technologies. This paper explains the relationships of TPX to the current US fusion physics program, to the ITER program, and to the development of an attractive tokamak demonstration plant for this next stage in the fusion program.

  4. The external kink mode in diverted tokamaks

    SciTech Connect

    Turnbull, Alan D.; Hanson, Jeremy M.; Turco, Francesca; Ferraro, Nathaniel M.; Lanctot, Matthew J.; Lao, Lang L.; Strait, Edward J.; Piovesan, Paolo; Martin, Piero

    2016-06-16

    Here, an explanation is provided for the disruptive instability in diverted tokamaks when the safety factor at the 95% poloidal flux surface, q95, is driven below 2.0. The instability is a resistive kink counterpart to the current-driven ideal mode that traditionally explained the corresponding disruption in limited cross-sections when qedge, the safety factor at the outermost closed flux surface, lies just below a rational value. Experimentally, external kink modes are observed in limiter configurations as the current in a tokamak is ramped up and qedge decreases through successive rational surfaces. For qedge < 2, the instability is always encountered and is highly disruptive. However, diverted plasmas, in which qedge is formally infinite in the magnetohydrodynamic (MHD) model, have presented a longstanding difficulty since the theory would predict stability, yet, the disruptive limit occurs in practice when q95, reaches 2. It is shown from numerical calculations that a resistive kink mode is linearly destabilized by the rapidly increasing resistivity at the plasma edge when q95 < 2, but qedge >> 2. The resistive kink behaves much like the ideal kink with predominantly kink or interchange parity and no real sign of a tearing component. However, the growth rates scale with a fractional power of the resistivity near the q = 2 surface. The results have a direct bearing on the conventional edge cutoff procedures used in most ideal MHD codes, as well as implications for ITER and for future reactor options.

  5. Self-organized stationary states of tokamaks

    NASA Astrophysics Data System (ADS)

    Jardin, Stephen

    2015-11-01

    We report here on a nonlinear mechanism that forms and maintains a self-organized stationary (sawtooth free) state in tokamaks. This process was discovered by way of extensive long-time simulations using the M3D-C1 3D extended MHD code in which new physics diagnostics have been added. It is well known that most high-performance modes of tokamak operation undergo ``sawtooth'' cycles, in which the peaking of the toroidal current density triggers a periodic core instability which redistributes the current density. However, certain modes of operation are known, such as the ``hybrid'' mode in DIII-D, ASDEX-U, JT-60U and JET, and the long-lived modes in NSTX and MAST, which do not experience this cycle of instability. Empirically, it is observed that these modes maintain a non-axisymmetric equilibrium which somehow limits the peaking of the toroidal current density. The physical mechanism responsible for this has not previously been understood, but is often referred to as ``flux-pumping,'' in which poloidal flux is redistributed in order to maintain q0 >1. In this talk, we show that in long-time simulations of inductively driven plasmas, a steady-state magnetic equilibrium may be obtained in which the condition q0 >1 is maintained by a dynamo driven by a stationary marginal core interchange mode. This interchange mode, unstable because of the pressure gradient in the ultra-low shear region in the center region, causes a (1,1) perturbation in both the electrostatic potential and the magnetic field, which nonlinearly cause a (0,0) component in the loop voltage that acts to sustain the configuration. This hybrid mode may be a preferred mode of operation for ITER. We present parameter scans that indicate when this sawtooth-free operation can be expected.

  6. Plasma diagnostics for the compact ignition tokamak

    SciTech Connect

    Medley, S.S.; Young, K.M.

    1988-06-01

    The primary mission of the Compact Ignition Tokamak (CIT) is to study the physics of alpha-particle heating in an ignited D-T plasma. A burn time of about 10 /tau//sub E/ is projected in a divertor configuration with baseline machine design parameters of R=2.10 m, 1=0.65 m, b=1.30 m, I/sub p/=11 MA, B/sub T/=10 T and 10-20 MW of auxiliary rf heating. Plasma temperatures and density are expected to reach T/sub e/(O) /approximately/20 keV, T/sub i/(O) /approximately/30 keV, and n/sub e/(O) /approximately/ 1 /times/ 10/sup 21/m/sup /minus/3/. The combined effects of restricted port access to the plasma, the presence of severe neutron and gamma radiation backgrounds, and the necessity for remote of in-cell components create challenging design problems for all of the conventional diagnostic associated with tokamak operations. In addition, new techniques must be developed to diagnose the evolution in space, time, and energy of the confined alpha distribution as well as potential plasma instabilities driven by collective alpha-particle effects. The design effort for CIT diagnostics is presently in the conceptual phase with activity being focused on the selection of a viable diagnostic set and the identification of essential research and development projects to support this process. A review of these design issues and other aspects impacting the selection of diagnostic techniques for the CIT experiment will be presented. 28 refs., 10 figs., 2 tabs.

  7. Dust Studies in DIII-D Tokamak

    SciTech Connect

    Rudakov, D L; West, W P; Groth, M; Yu, J H; Boedo, J A; Bray, B D; Brooks, N H; Fenstermacher, M E; Hollmann, E M; Hyatt, A W; Krasheninnikov, S I; Lasnier, C J; Moyer, R A; Pigarov, A Y; Smirnov, R; Solomon, W M; Wong, C C

    2008-04-15

    Studies of submicron dust using Mie scattering from Nd:YAG lasers and video data of micron to sub-millimeter sized dust on DIII-D tokamak have provided the first data of dust sources and transport during tokamak discharges. During normal operation on DIII-D dust observation rates are low, a few events per discharge or less. The net carbon content of the dust corresponds to a carbon atom density a few orders of magnitude below the core impurity density. Statistical analysis of Mie data collected over months of operation reveal correlation of increased dust rate with increased heating power and impulsive wall loading due to edge localized modes (ELMs) and disruptions. Generation of significant amounts of dust by disruptions is confirmed by the camera data. However, dust production by disruptions alone is insufficient to account for estimated in-vessel dust inventory in DIII-D. After an extended entry vent, thousands of dust particles are observed by cameras in the first 2-3 plasma discharges. Individual particles moving at velocities up to {approx}300 m/s, breakup of larger particles into pieces, and collisions of particles with walls are observed. After {approx}70 discharges, dust levels are reduced to a few events per discharge. In order to calibrate diagnostics and benchmark modeling, milligram amounts of micron-sized carbon dust have been injected into DIII-D discharges, leading to the core carbon density increase by a factor of 2-3. Following injection, dust trajectories in the divertor are mostly in the toroidal direction, consistent with the ion drag force. Dust from the injection is observed in the outboard midplane by a fast framing camera. The observed trajectories and velocities of the dust particles are in qualitative agreement with modeling by the 3D DustT code.

  8. Vertical compact torus injection into the STOR-M tokamak

    NASA Astrophysics Data System (ADS)

    Liu, Dazhi

    Central fuelling is a fundamental issue in the next generation tokamak-ITER (International Thermonuclear Experimental Reactor). It is essential for optimization of the bootstrap current which is proportional to the pressure gradient of trapped particles. The conventional fusion reactor fuelling techniques, such as gas puffing and cryogenic pellet injection, are considered inadequate to fulfill this goal due to premature ionization caused by high plasma temperature and density. Compact Torus (CT) injection is a promising fuelling technique for central fuelling a reactor-grade tokamak. An accelerated CT is expected to penetrate into the core region and deposit fuel there provided the CT kinetic energy density exceeds the magnetic energy density in a target plasma. This process is complicated and involves CT penetration into an external magnetic field, a CT stopping mechanism, magnetic reconnection, and excitation of plasma waves. CTs can be injected at different angles with respect to the tokamak toroidal magnetic field, either horizontally or vertically. Normally, CTs are injected radially in the mid-plane of a tokamak. In this configuration, CTs will undergo a decelerating force due to the gradient of the tokamak toroidal magnetic field. CTs will stop inside the tokamak chamber or bunce back depending on the relation between kinetic energy density of injected CTs and the tokamak toroidal magnetic field energy density. In the case of vertical injection, deeper penetration is expected due to the absence of the gradient of the tokamak toroidal field in that direction. Experimental investigations on vertical CT injection into a tokamak will be of great significance. The aim of this thesis is to experimentally investigate the feasibility of vertical CT injection into a tokamak and effects of CTs on tokamak plasma confinements. The Saskatchewan Torus-Modified (STOR-M) tokamak is currently the only tokamak equipped with a CT injector in the world. Vertical CT injection

  9. LONG PULSE ADVANCED TOKAMAK DISCHARGES IN THE DIII-D TOKAMAK

    SciTech Connect

    P.I. PETERSEN

    2002-06-01

    One of the main goals for the DIII-D research program is to establish an advanced tokamak plasma with high bootstrap current fraction that can be sustained in-principle steady-state. Substantial progress has been made in several areas during the last year. The resistive wall mode stabilization has been done with spinning plasmas in which the plasma pressure has been extended well above the no-wall beta limit. The 3/2 neoclassical tearing mode has been stabilized by the injection of ECH into the magnetic islands, which drives current to substitute the missing bootstrap current. In these experiments either the plasma was moved or the toroidal field was changed to overlap the ECCD resonance with the location of the NTMs. Effective disruption mitigation has been obtained by massive noble gas injection into shots where disruptions were deliberately triggered. The massive gas puff causes a fast and clean current quench with essentially all the plasma energy radiated fairly uniformly to the vessel walls. The run-away electrons that are normally seen accompanying disruptions are suppressed by the large density of electrons still bound on the impurity nuclei. Major elements required to establish integrated, long-pulse, advanced tokamak operations have been achieved in DIII-D: {beta}{sub T} = 4.2%, {beta}{sub p} = 2, f{sub BS} = 65%, and {beta}{sub N}H{sub 89} = 10 for 600 ms ({approx} 4{tau}{sub E}). The next challenge is to integrate the different elements, which will be the goal for the next five years when additional control will be available. Twelve resistive wall mode coils are scheduled to be installed in DIII-D during the summer of 2003. The future plans include upgrading the tokamak pulse length capability and increasing the ECH power, to control the current profile evolution.

  10. Magnetic Flux Reconstruction Methods for Shaped Tokamaks

    NASA Astrophysics Data System (ADS)

    Tsui, Chi-Wa.

    The use of a variational method permits the Grad -Shafranov (GS) equation to be solved by reducing the problem of solving the 2D non-linear partial differential equation to the problem of minimizing a function of several variables. This high speed algorithm approximately solves the GS equation given a pararmeterization of the plasma boundary and the current profile (p^' and FF^' functions). We treat the current profile parameters as unknowns. The goal is to reconstruct the internal magnetic flux surfaces of a tokamak plasma and the toroidal current density profile from the external magnetic measurements. This is a classic problem of inverse equilibrium determination. The current profile parameters can be evaluated by several different matching procedures. We found that the matching of magnetic flux and field at the probe locations using the Biot-Savart law and magnetic Green's function provides a robust method of magnetic reconstruction. The matching of poloidal magnetic field on the plasma surface provides a unique method of identifying the plasma current profile. However, the power of this method is greatly compromised by the experimental errors of the magnetic signals. The Casing Principle (60) provides a very fast way to evaluate the plasma contribution to the magnetic signals. It has the potential of being a fast matching method. We found that the performance of this method is hindered by the accuracy of the poloidal magnetic field computed from the equilibrium solver. A flux reconstruction package have been implemented which integrates a vacuum field solver using a filament model for the plasma, a multi-layer perceptron neural network as a interface, and the volume integration of plasma current density using Green's functions as a matching method for the current profile parameters. The flux reconstruction package is applied to compare with the ASEQ and EFIT data. The results are promising. Also, we found that some plasmas in the tokamak Alcator C-Mod lie

  11. Magnetic control of magnetohydrodynamic instabilities in tokamaks

    NASA Astrophysics Data System (ADS)

    Strait, E. J.

    2015-02-01

    Externally applied, non-axisymmetric magnetic fields form the basis of several relatively simple and direct methods to control magnetohydrodynamic (MHD) instabilities in a tokamak, and most present and planned tokamaks now include a set of non-axisymmetric control coils for application of fields with low toroidal mode numbers. Non-axisymmetric applied fields are routinely used to compensate small asymmetries ( δB /B ˜10-3 to 10-4 ) of the nominally axisymmetric field, which otherwise can lead to instabilities through braking of plasma rotation and through direct stimulus of tearing modes or kink modes. This compensation may be feedback-controlled, based on the magnetic response of the plasma to the external fields. Non-axisymmetric fields are used for direct magnetic stabilization of the resistive wall mode—a kink instability with a growth rate slow enough that feedback control is practical. Saturated magnetic islands are also manipulated directly with non-axisymmetric fields, in order to unlock them from the wall and spin them to aid stabilization, or position them for suppression by localized current drive. Several recent scientific advances form the foundation of these developments in the control of instabilities. Most fundamental is the understanding that stable kink modes play a crucial role in the coupling of non-axisymmetric fields to the plasma, determining which field configurations couple most strongly, how the coupling depends on plasma conditions, and whether external asymmetries are amplified by the plasma. A major advance for the physics of high-beta plasmas ( β = plasma pressure/magnetic field pressure) has been the understanding that drift-kinetic resonances can stabilize the resistive wall mode at pressures well above the ideal-MHD stability limit, but also that such discharges can be very sensitive to external asymmetries. The common physics of stable kink modes has brought significant unification to the topics of static error fields at low

  12. Magnetic control of magnetohydrodynamic instabilities in tokamaks

    SciTech Connect

    Strait, Edward J.

    2014-11-24

    Externally applied, non-axisymmetric magnetic fields form the basis of several relatively simple and direct methods to control magnetohydrodynamic (MHD) instabilities in a tokamak, and most present and planned tokamaks now include a set of non-axisymmetric control coils for application of fields with low toroidal mode numbers. Non-axisymmetric applied fields are routinely used to compensate small asymmetries ( δB/B ~ 10-3 to 10-4) of the nominally axisymmetric field, which otherwise can lead to instabilities through braking of plasma rotation and through direct stimulus of tearing modes or kink modes. This compensation may be feedback-controlled, based on the magnetic response of the plasma to the external fields. Non-axisymmetric fields are used for direct magnetic stabilization of the resistive wall mode — a kink instability with a growth rate slow enough that feedback control is practical. Saturated magnetic islands are also manipulated directly with non-axisymmetric fields, in order to unlock them from the wall and spin them to aid stabilization, or position them for suppression by localized current drive. Several recent scientific advances form the foundation of these developments in the control of instabilities. Most fundamental is the understanding that stable kink modes play a crucial role in the coupling of non-axisymmetric fields to the plasma, determining which field configurations couple most strongly, how the coupling depends on plasma conditions, and whether external asymmetries are amplified by the plasma. A major advance for the physics of high-beta plasmas ( β = plasma pressure/magnetic field pressure) has been the understanding that drift-kinetic resonances can stabilize the resistive wall mode at pressures well above the ideal-MHD stability limit, but also that such discharges can be very sensitive to external asymmetries. The common physics of stable kink modes has brought significant unification to the topics of static

  13. Magnetic control of magnetohydrodynamic instabilities in tokamaks

    DOE PAGES

    Strait, Edward J.

    2014-11-24

    Externally applied, non-axisymmetric magnetic fields form the basis of several relatively simple and direct methods to control magnetohydrodynamic (MHD) instabilities in a tokamak, and most present and planned tokamaks now include a set of non-axisymmetric control coils for application of fields with low toroidal mode numbers. Non-axisymmetric applied fields are routinely used to compensate small asymmetries ( δB/B ~ 10-3 to 10-4) of the nominally axisymmetric field, which otherwise can lead to instabilities through braking of plasma rotation and through direct stimulus of tearing modes or kink modes. This compensation may be feedback-controlled, based on the magnetic response of themore » plasma to the external fields. Non-axisymmetric fields are used for direct magnetic stabilization of the resistive wall mode — a kink instability with a growth rate slow enough that feedback control is practical. Saturated magnetic islands are also manipulated directly with non-axisymmetric fields, in order to unlock them from the wall and spin them to aid stabilization, or position them for suppression by localized current drive. Several recent scientific advances form the foundation of these developments in the control of instabilities. Most fundamental is the understanding that stable kink modes play a crucial role in the coupling of non-axisymmetric fields to the plasma, determining which field configurations couple most strongly, how the coupling depends on plasma conditions, and whether external asymmetries are amplified by the plasma. A major advance for the physics of high-beta plasmas ( β = plasma pressure/magnetic field pressure) has been the understanding that drift-kinetic resonances can stabilize the resistive wall mode at pressures well above the ideal-MHD stability limit, but also that such discharges can be very sensitive to external asymmetries. The common physics of stable kink modes has brought significant unification to the topics of static error fields

  14. Magnetic control of magnetohydrodynamic instabilities in tokamaks

    SciTech Connect

    Strait, E. J.

    2015-02-15

    Externally applied, non-axisymmetric magnetic fields form the basis of several relatively simple and direct methods to control magnetohydrodynamic (MHD) instabilities in a tokamak, and most present and planned tokamaks now include a set of non-axisymmetric control coils for application of fields with low toroidal mode numbers. Non-axisymmetric applied fields are routinely used to compensate small asymmetries (δB/B∼10{sup −3} to 10{sup −4}) of the nominally axisymmetric field, which otherwise can lead to instabilities through braking of plasma rotation and through direct stimulus of tearing modes or kink modes. This compensation may be feedback-controlled, based on the magnetic response of the plasma to the external fields. Non-axisymmetric fields are used for direct magnetic stabilization of the resistive wall mode—a kink instability with a growth rate slow enough that feedback control is practical. Saturated magnetic islands are also manipulated directly with non-axisymmetric fields, in order to unlock them from the wall and spin them to aid stabilization, or position them for suppression by localized current drive. Several recent scientific advances form the foundation of these developments in the control of instabilities. Most fundamental is the understanding that stable kink modes play a crucial role in the coupling of non-axisymmetric fields to the plasma, determining which field configurations couple most strongly, how the coupling depends on plasma conditions, and whether external asymmetries are amplified by the plasma. A major advance for the physics of high-beta plasmas (β = plasma pressure/magnetic field pressure) has been the understanding that drift-kinetic resonances can stabilize the resistive wall mode at pressures well above the ideal-MHD stability limit, but also that such discharges can be very sensitive to external asymmetries. The common physics of stable kink modes has brought significant unification to the topics of static error

  15. Basic Physics of Tokamak Transport Final Technical Report.

    SciTech Connect

    Sen, Amiya K.

    2014-05-12

    The goal of this grant has been to study the basic physics of various sources of anomalous transport in tokamaks. Anomalous transport in tokamaks continues to be one of the major problems in magnetic fusion research. As a tokamak is not a physics device by design, direct experimental observation and identification of the instabilities responsible for transport, as well as physics studies of the transport in tokamaks, have been difficult and of limited value. It is noted that direct experimental observation, identification and physics study of microinstabilities including ITG, ETG, and trapped electron/ion modes in tokamaks has been very difficult and nearly impossible. The primary reasons are co-existence of many instabilities, their broadband fluctuation spectra, lack of flexibility for parameter scans and absence of good local diagnostics. This has motivated us to study the suspected tokamak instabilities and their transport consequences in a simpler, steady state Columbia Linear Machine (CLM) with collisionless plasma and the flexibility of wide parameter variations. Earlier work as part of this grant was focused on both ITG turbulence, widely believed to be a primary source of ion thermal transport in tokamaks, and the effects of isotope scaling on transport levels. Prior work from our research team has produced and definitively identified both the slab and toroidal branches of this instability and determined the physics criteria for their existence. All the experimentally observed linear physics corroborate well with theoretical predictions. However, one of the large areas of research dealt with turbulent transport results that indicate some significant differences between our experimental results and most theoretical predictions. Latter years of this proposal were focused on anomalous electron transport with a special focus on ETG. There are several advanced tokamak scenarios with internal transport barriers (ITB), when the ion transport is reduced to

  16. Initial boronization of the DIII-D tokamak

    SciTech Connect

    Phillips, J.; Hodapp, T.; Holtrop, K.; Jackson, G.; Winter, J.

    1991-10-01

    A system has been installed to deposit a thin film of elemental boron to the walls of the D3-D tokamak, in order to reduce the influx of impurities during plasma discharges. Subsequently new regimes of substantially tokamak energy confinement were obtained. The deposition of the boron layer is achieved during a glow-discharge session using a helium-diborane age mixture and a film of {approx}100 nm is deposited. The boronization system includes special storage and handling precautions for the diborane, a delivery and metering system for the glow-discharge, modifications to the tokamak's residual gas analyzer system, and a dedicated system for handling and neutralizing the exhaust gas from the tokamak. Tokamak discharges with similar parameters before and after boronization are used to characterize the effects of the boron film. Nickel has been reduced by a factor of 30, while impurities such as oxygen and carbon are reduced fivefold. A system of pulsing the flow discharge has been developed in order to improve the uniformity of the film applied.

  17. Magnetic Start-up Inducement in NOVILLO Tokamak

    NASA Astrophysics Data System (ADS)

    Melendez-Lugo, Leandro; Chavez, Esteban; Barocio, Samuel R.; Flores, Angel; Cruz, Guillermo J.; Guadalupe Olayo, M.

    2000-10-01

    Most tokamak devices require one or more breakdown assistance systems, such as particles or ECRH radiation, in order to develop plasma discharges by increasing the probabilities of ionization. In smaller tokamaks filament preionization traditionally primes the start-up, reducing the required amounts of loop voltage and OHT flux consumption. Yet, the latter not only may result obtrusive to the operational access but also its incandescence contributes to raise the plasma impurity levels. A new vertical field profile, superimposed to the stray field component parallel to the equilibrium field, has been created in NOVILLO tokamak by means of two additional compensation poloidal coils. Such arrangement of the vertical field profiles, with an 1/R-dependence, has been found adequate to achieve the plasma breakdown without any preionization system. Furthermore, evidence has been gathered indicating that tokamak discharges achieved by vertical stray field modification instead of preionization allow to operate with higher prefill pressure and therefore to create denser plasmas at standard loop voltage levels. A technique like the one presented here may prove suitable to accomplish dependable discharges on large tokamaks while saving costs considerably. Likewise this technique is feasible to be applied successfully in general toroidal gas breakdown and arcing processes.

  18. Power supplies and quench protection for the Tokamak Physics Experiment

    SciTech Connect

    Neumeyer, C.L.

    1994-07-01

    The Tokamak Physics Experiment (TPX) is an advanced tokamak project aimed at the production of quasi-steady state plasmas with advanced shape, heating, and particle control. TPX is to be built at the Princeton Plasma Physics Laboratory (PPPL) using many of the facilities from the Tokamak Fusion Test Reactor (TFTR). First plasma is scheduled for the year 2000. TPX will be the first tokamak to utilize superconducting (SC) magnets in both the toroidal field (TF) and poloidal field (PF) systems. This is a new feature which requires not only a departure from the traditional tokamak power supply schemes but also that ultra-reliable quench protection devices be used to rapidly discharge the stored energy from the magnets in the event of a quench. This paper describes the plan and basis for the adaptation and augmentation of the PPPL/TFTR power system facilities to supply TPX. Following a description of the basic operational requirements, four major areas are addressed, namely the AC power system, the TF power supply, the PF power supply, and quench protection for the TF and PF systems.

  19. Power supplies and quench protection for the Tokamak Physics Experiment

    SciTech Connect

    Neumeyer, C.L.

    1994-11-01

    The Tokamak Physics Experiment (TPX) is an advanced tokamak project aimed at the production of quasi-steady state plasmas with advanced shape, heating, and particle control. TPX is to be built at the Princeton Plasma Physics Laboratory (PPPL) using many of the facilities from the Tokamak Fusion Test Reactor (TFTR). First plasma is scheduled for the year 2000. TPX will be the first tokamak to utilize superconducting (SC) magnets in both the toroidal field (TF) and poloidal field (PF) systems. This is a new feature which requires not only a departure from the traditional tokamak power supply schemes but also that ultra-reliable quench protection devices be used to rapidly discharge the stored energy from the magnets in the event of a quench. This paper describes the plan and basis for the adaptation and augmentation of the PPPL/TFTR power system facilities to supply TPX. Following a description of the basic operational requirements, four major areas are addressed, namely the AC power system, the TF power supply, the PF power supply, and quench protection for the TF and PF systems.

  20. Excess-density-driven snakes in tokamaks

    NASA Astrophysics Data System (ADS)

    Aydemir, A. Y.; Shaing, K. C.; Waelbroeck, F. L.

    2011-10-01

    ``Snakes'' refer to sinusoidal patterns observed on space-time plots of soft-X-ray signals in tokamak plasmas. They are generally attributed to persistent and localized density perturbations that form at a rational surface after pellet injection (Weller, JET 1987), and Parker, Alcator-C 1987), or impurity accumulation (Naujoks, ASDEX 1996, Delgado-Aparicio, C-Mod 2011). It is not clear whether all snake observations have a unique origin. A likely explanation is that material trapped inside an island driven by a temperature hole leads to the observed soft-X-ray signals (Wesson 1995). More recently, it has been suggested that they could be the result of saturated nonlinear internal kinks in low, or reversed-shear geometries (Cooper 2011). We have started an examination of some of these issues using ideas from neoclassical transport theory (Shaing 2007) in conjunction with various magnetohydrodynamic models. In a RMHD model, we demonstrated that excess-density-driven bootstrap current can stabilize a resistive m = 1 island at a small amplitude, leaving a radially and poloidally localized snake-like structure. Extension of this work to more sophisticated models that include diamagnetic effects, and possibly more realistic geometries, will be presented. This research was supported by the Office of Fusion Energy Science of the U.S. Department of Energy.

  1. Tearing mode analysis in tokamaks, revisited

    SciTech Connect

    Nishimura, Y.; Callen, J.D.; Hegna, C.C.

    1997-12-01

    A new {Delta}{prime} shooting code has been developed to investigate tokamak plasma tearing mode stability in a cylinder and large aspect ratio ({epsilon} {le} 0.25) toroidal geometries, neglecting toroidal mode coupling. A different computational algorithm is used (shooting out from the singular surface instead of into it) to resolve the strong singularities at the mode rational surface, particularly in the presence of finite pressure term. Numerical results compare favorably with Furth et al. results. The effects of finite pressure, which are shown to decrease {Delta}{prime}, are discussed. It is shown that the distortion of the flux surfaces by the Shafranov shift, which modifies the geometry metric element stabilizes the tearing mode significantly, even in a low {beta} regime before the toroidal magnetic curvature effects come into play. Double tearing modes in toroidal geometries are examined as well. Furthermore, m {ge} 2 tearing mode stability criteria are compared with three dimensional initial value MHD simulation by the FAR code.

  2. Neoclassical transport of impurtities in tokamak plasmas

    SciTech Connect

    Hirshman, S.P.; Sigmar, D.J.

    1981-05-01

    Tokamak plasmas are inherently comprised of multiple ion species. This is due to wall-bred impurities and, in future reactors, will result from fusion-born alpha particles. Relatively small concentrations of highly charged non-hydrogenic impurities can strongly influence plasma transport properties whenever n/sub I/e/sub I//sup 2//n/sub H/e/sup 2/ greater than or equal to (m/sub e//m/sub H/)/sup 1/2/. The determination of the complete neoclassical Onsager matrix for a toroidally confined multispecies plasma, which provides the linear relation between the surface averaged radial fluxes and the thermodynamic forces (i.e., gradients of density and temperature, and the parallel electric field), is reviewed. A closed set of one-dimensional moment equations is presented for the time evolution of thermodynamic and magnetic field quantities which results from collisional transport of the plasma and two dimensional motion of the magnetic flux surface geometry. The effects of neutral beam injection on the equilibrium and transport properties of a toroidal plasma are consistently included.

  3. Divertor design for the Tokamak Physics Experiment

    SciTech Connect

    Hill, D.N.; Braams, B.; Brooks, J.N.

    1994-05-01

    In this paper we discuss the present divertor design for the planned TPX tokamak, which will explore the physics and technology of steady-state (1000s pulses) heat and particle removal in high confinement (2--4{times} L-mode), high beta ({beta}{sub N} {ge} 3) divertor plasmas sustained by non-inductive current drive. The TPX device will operate in the double-null divertor configuration, with actively cooled graphite targets forming a deep (0.5 m) slot at the outer strike point. The peak heat flux on, the highly tilted (74{degrees} from normal) re-entrant (to recycle ions back toward the separatrix) will be in the range of 4--6 MW/m{sup 2} with 18 MW of neutral beams and RF heating power. The combination of active pumping and gas puffing (deuterium plus impurities), along with higher heating power (45 MW maximum) will allow testing of radiative divertor concepts at ITER-like power densities.

  4. Ionization balance in EBIT and tokamak plasmas

    NASA Astrophysics Data System (ADS)

    Peacock, N. J.; Barnsley, R.; O'Mullane, M. G.; Tarbutt, M. R.; Crosby, D.; Silver, J. D.; Rainnie, J. A.

    2001-01-01

    The equilibrium state in tokamak core plasmas has been studied using the relative intensities of resonance x-ray lines, for example Lyα (H-like), "w" (He-like), and "q" (Li-like) from test ions such as Ar+15, Ar+16, and Ar+17. A full spatial analysis involves comparison of the line intensities with ion diffusion calculations, including relevant atomic rates. A zero-dimensional model using a global ion loss rate approximation has also been demonstrated by comparison with the data collected from a Johann configuration spectrometer with a charged coupled device (CCD) detector. Since the lines are nearly monoenergetic, their intensities are independent of the instrument sensitivity and are directly proportional to the ion abundances. This method has recently been applied to Ar in the Oxford electron beam ion trap (EBIT) with a beam energy in the range 3-10 keV. Taking into account the cross sections for monoenergetic electron collisions and polarization effects, model calculations agree with the observed line ratios at 4.1 keV beam energy. This work will be expanded to provide nomograms of ionization state versus line intensity ratios as a function of EBIT beam energy.

  5. Forced magnetic reconnection in Tokamak plasmas

    NASA Astrophysics Data System (ADS)

    Cole, Andrew Joseph

    This dissertation addresses two related problems in the study of forced magnetic reconnection in Tokamak plasmas. First, a recent controversy concerning a model forced magnetic reconnection problem, the Taylor problem, has been resolved. The criticisms of Ishizawa and Tokuda [21] concerning the original analysis of Hahm and Kulsrud [17] are shown to be unwarranted, both analytically and numerically. Second, one possible reason for the discrepancy between recent experimental [29] and previous theoretical [13] scaling of the critical error-field penetration threshold with device parameters is addressed. The theory in question is entirely based on a single-fluid MHD (magnetohydrodynamical) treatment of the plasma. As is well-known, high temperature plasmas are far better modeled using the drift-MHD ordering.[18] Hence we develop a drift-MHD theory of error-field penetration. Although two new drift-MHD plasma response regimes are identified, the overall threshold scaling with device parameters is not altogether different from that predicted by single-fluid MHD.

  6. Quasicoherent modes on the COMPASS tokamak

    NASA Astrophysics Data System (ADS)

    Melnikov, A. V.; Markovic, T.; Eliseev, L. G.; Adámek, J.; Aftanas, M.; Bilkova, P.; Boehm, P.; Gryaznevich, M.; Imrisek, M.; Lysenko, S. E.; Medvedev, S. Y.; Panek, R.; Peterka, M.; Seidl, J.; Stefanikova, E.; Stockel, J.; Weinzettl, V.; the COMPASS Team

    2015-06-01

    Multiple quasicoherent electromagnetic modes with steady-state frequency and different nature and location were observed in the COMPASS tokamak (R = 0.56 m, = 0.2 m) at Bt = 1.14 T with Co-NBI (PNBI = 0.2-0.5 MW, Eb = 32 keV) at frequencies 5 kHz < f < 250 kHz. Modes were observed in both low and high confinement (L- and H-modes) plasmas. Lower frequency modes with f < 50 kHz were identified as low m tearing and kink MHD modes, while higher frequency modes with 50 kHz < f < 250 kHz were considered as having Alfvénic nature. Unexpectedly, such modes were only observed in the H-mode, both in neutral beam injector-assisted and Ohmic, so the mode driving force is not yet clear. Using the linear MHD code KINX, we initially identified the observed mode with a ballooning structure is as beta induced Alfvén eigenmode (BAE) with m, n < 5, while an antiballooning mode is initially identified as toroidal Alfvén eigenmode (TAE) with m, n < 9.

  7. Thermo-Oxidation of Tokamak Carbon Dust

    SciTech Connect

    J.W. Davis; B.W.N. Fitzpatrick; J.P. Sharpe; A.A. Haasz

    2008-04-01

    The oxidation of dust and flakes collected from the DIII-D tokamak, and various commercial dust specimens, has been measured at 350 ºC and 2.0 kPa O2 pressure. Following an initial small mass loss, most of the commercial dust specimens showed very little effect due to O2 exposure. Similarly, dust collected from underneath DIII-D tiles, which is thought to comprise largely Grafoil™ particulates, also showed little susceptibility to oxidation at this temperature. However, oxidation of the dust collected from tile surfaces has led to ~ 18% mass loss after 8 hours; thereafter, little change in mass was observed. This suggests that the surface dust includes some components of different composition and/or structure – possibly fragments of codeposited layers. The oxidation of codeposit flakes scraped form DIII-D upper divertor tiles showed an initial 25% loss in mass due to heating in vacuum, and the gradual loss of 30-38% mass during the subsequent 24 hours exposure to O2. This behavior is significantly different from that observed for the oxidation of thinner DIII-D codeposit specimens which were still adhered to tile surfaces, and this is thought to be related to the low deuterium content (D/C ~ 0.03 – 0.04) of the flakes.

  8. ELM experimental study on the EAST Tokamak

    NASA Astrophysics Data System (ADS)

    Liu, Zixi; Gao, Xiang; Xu, Xueqiao; Li, Jiangang; EAST Team

    2013-10-01

    Atypical Type III ELM is observed on EAST tokamak. This type of ELM has MHD precursor and high collisionality at the edge, and also the threshold power is close to the scaling law. But the frequency of the ELM does not decrease with the injected power. Power threshold is lower with the molybdenum wall in double null (DN) on EAST. Considering the effects of the plasma surface (S) to the threshold power, Double Null has the lowest power threshold. Better energy confinement has been observed in DN compared to Single-null (SN) at same power loss. But with the same power loss, Upper Single Null (USN) with the grad-B drift pointing backwards the active X-point (favorable direction) on EAST has the lower energy confinement time than Lower Single Null (LSN). Low Hybrid Wave (LHW) can mitigate ELMs. The power deposition should be near the edge in the H-mode phase. Not only the LHW decreases the max gradient of the density in the pedestal region, but also brings the density oscillations. Low X-point configurations in Lower single null have a lower power threshold. The low X-point discharges on EAST is closer to the DN. Approaching to the DN configuration should be the reason of the lower power threshold caused by the lower X-point on EAST.

  9. Global Geodesic Acoustic Modes in Tokamak Plasmas

    NASA Astrophysics Data System (ADS)

    Sorokina, Ekaterina; Ilgisonis, Viktor; Lakhin, Vladimir; Smolyakov, Andrey; Khalzov, Ivan

    2010-11-01

    Global Geodesic Acoustic Modes (GGAM) in Tokamak Plasmas are investigated in the framework of reduced ideal MHD. The axisymmetric eigenvalue problem for perturbed pressure and electrostatic potential is formulated as a recurrent set of equations for poloidal Fourier harmonics. For uniform safety factor q and temperature profile with a maximum at radius r=r0!=0 the analytical solution of this eigenvalue problem is obtained for a truncated set of equations taking into account the m=0 and m=2 poloidal harmonics of potential and the m=1 harmonic of pressure. This solution exists in wide range of βq^2. It is shown both analytically and numerically that the higher harmonics of pressure (m=3) and electrostatic potential (m=4) reduce the range of the parameters, in which GGAM exist, due to the resonance with continuum spectrum. The domain of GGAM existence in the (βq^2, r0)-plane is represented. Higher poloidal harmonics (m>4) are shown to weakly affect the GAM spectrum and do not lead to the appearance of other global eigenmodes. The work is supported in part by grant RBRF 10-02-01302 and by Ministry of Education and Science of the RF, contract 1.5-508-008-045.

  10. Nonlinear fishbone dynamics in spherical tokamaks

    NASA Astrophysics Data System (ADS)

    Wang, Feng; Fu, G. Y.; Shen, Wei

    2017-01-01

    Linear and nonlinear kinetic-MHD hybrid simulations have been carried out to investigate linear stability and nonlinear dynamics of beam-driven fishbone instability in spherical tokamak plasmas. Realistic NSTX parameters with finite toroidal rotation were used. The results show that the fishbone is driven by both trapped and passing particles. The instability drive of passing particles is comparable to that of trapped particles in the linear regime. The effects of rotation are destabilizing and a new region of instability appears at higher q min (>1.5) values, q min being the minimum of safety factor profile. In the nonlinear regime, the mode saturates due to flattening of beam ion distribution, and this persists after initial saturation while mode frequency chirps down in such a way that the resonant trapped particles move out radially and keep in resonance with the mode. Correspondingly, the flattening region of beam ion distribution expands radially outward. A substantial fraction of initially non-resonant trapped particles become resonant around the time of mode saturation and keep in resonance with the mode as frequency chirps down. On the other hand, the fraction of resonant passing particles is significantly smaller than that of trapped particles. Our analysis shows that trapped particles provide the main drive to the mode in the nonlinear regime.

  11. Tokamak L/H mode transition

    SciTech Connect

    Tsui, K. H.; Navia, C. E.

    2012-01-15

    Through the non field-aligned rotational tokamak equilibrium of a divergence-free plasma flow with a pair of transformed plasma variables w-vector{sub *}=({mu}{rho}){sup 1/2}{nu}-vector and {mu}p{sub *}=({mu}p+w{sub *}{sup 2}/2)[K. H. Tsui, Phys. Plasmas 18, 072502 (2011)], a preliminary understanding of the L/H equilibrium transition is proposed through a feedback cycle, where the higher plasma flux due to external drives enters the rotational Grad-Shafranov equation through the velocity dependent poloidal plasma {beta} to generate the H equilibrium. This H rotational mode has the characteristics of higher normal electric field and plasma pressure. Coupled to the transport properties of E-vector x B-vector drift transport barrier leading to a higher plasma pressure, this makes the H mode a self-sustained equilibrium. The higher plasma {beta} then feeds back to the equilibrium and completes the feedback loop.

  12. Physics aspects of the Compact Ignition Tokamak

    SciTech Connect

    Post, D.; Bateman, G.; Houlberg, W.; Bromberg, L.; Cohn, D.; Colestock, P.; Hughes, M.; Ignat, D.; Izzo, R.; Jardin, S.

    1986-11-01

    The Compact Ignition Tokamak (CIT) is a proposed modest-size ignition experiment designed to study the physics of alpha-particle heating. The basic concept is to achieve ignition in a modest-size minimum cost experiment by using a high plasma density to achieve the condition of ntau/sub E/ approx. 2 x 10/sup 20/ sec m/sup -3/ required for ignition. The high density requires a high toroidal field (10 T). The high toroidal field allows a large plasma current (10 MA) which improves the energy confinement, and provides a high level of ohmic heating. The present CIT design also has a gigh degree of elongation (k approx. 1.8) to aid in producing the large plasma current. A double null poloidal divertor and a pellet injector are part of the design to provide impurity and particle control, improve the confinement, and provide flexibility for impurity and particle control, improve the confinement, and provide flexibility for improving the plasma profiles. Since auxiliary heating is expected to be necessary to achieve ignition, 10 to 20 MW of Ion Cyclotron Radio Frequency (ICRF) is to be provided.

  13. Zonal flows in tokamaks with anisotropic pressure

    SciTech Connect

    Ren, Haijun

    2014-04-15

    Zonal flows (ZFs) in a tokamak plasma with anisotropic pressure are investigated. The dynamics of perpendicular and parallel pressures are determined by the Chew-Goldberger-Low double equations and low-β condition is adopted, where β is the ratio of plasma pressure to the magnetic field pressure. The dispersion relation is analytically derived and illustrates two branches of ZFs. The low frequency zonal flow (LFZF) branch becomes unstable when χ, the ratio of the perpendicular pressure to the parallel one, is greater than a threshold value χ{sub c}, which is about 3.8. In the stable region, its frequency increases first and then decreases with increasing χ. For χ = 1, the frequency of LFZF agrees well with the experimental observation. For the instability, the growth rate of LFZF increases with χ. The geodesic acoustic mode branch is shown to be always stable with a frequency increasing with χ. The safety factor is shown to diminish the frequencies of both branches or the growth rate of LFZF.

  14. Fast bolometric measurements on the TCV tokamak

    NASA Astrophysics Data System (ADS)

    Furno, I.; Weisen, H.; Mlynar, J.; Pitts, R. A.; Llobet, X.; Marmillod, Ph.; Pochon, G. P.

    1999-12-01

    The design and first results are presented from a bolometric diagnostic with high temporal resolution recently installed on the TCV tokamak. The system consists of two pinhole cameras viewing the plasma from above and below at the same toroidal location. Each camera is equipped with an AXUV-16ELO linear array of 16 p-n junction photodiodes, characterized by a flat spectral sensitivity from ultraviolet to x-ray energies, a high temporal response (<0.5 μs), and insensitivity to low-energy neutral particles emitted by the plasma. This high temporal resolution allows the study of transient phenomena such as fast magnetohydrodynamic (MHD) activity hitherto inaccessible with standard bolometry. In the case of purely electromagnetic radiation, good agreement has been found when comparing results from the new diagnostic with those from a standard metal foil bolometer system. This comparison has also revealed that the contribution of neutrals to the foil bolometer measurements can be extremely important under certain operating conditions, precluding the application of tomographic techniques for reconstruction of the radiation distribution.

  15. Construction of the Lithium Tokamak Experiment (LTX)

    NASA Astrophysics Data System (ADS)

    Kozub, Thomas; Majeski, Richard; Kaita, Robert; Berzak, Laura; Lundberg, Daniel; Strickler, Trevor; Woolley, Robert; Zakharov, Leonid

    2008-11-01

    The Lithium Tokamak eXperiment (LTX)* will investigate the low recycling operating regime for magnetically confined plasmas using liquid lithium plasma facing surfaces. The engineering design and machine fabrication process will be presented. The most significant new feature of the LTX machine is the installation of a heated copper toroidal shell that will be operated at 300 C to 500 C. Its stainless steel plasma-facing liner will be internally coated with an evaporated layer of liquid lithium. The shell is comprised of four quadrants that have been fabricated in-house from explosively bonded stainless steel on copper to conform closely to the outer plasma flux surface. All internal components of the LTX machine have been designed and built to meet the simultaneous requirements for liquid lithium compatibility, high temperature operation, and electrical isolation. These requirements have led to unique design features, such as the method of supporting the shell quadrants, and construction of the new internal poloidal field coils. *Supported by US DOE contract #DE-AC02-76CH-03073

  16. Industry roles in the Tokamak Physics Experiment

    SciTech Connect

    Thomassen, K.I.

    1994-09-01

    The Tokamak Physics Experiment (TPX) is the first major fusion project opportunity in many years for US industry. Both the TPX management and the Department of Energy`s Office of Fusion Energy are committed to creating industry roles that are integrated throughout the project and that appropriately use the capabilities they offer. To address industry roles in TPX it is first appropriate to describe the collaborative national approach taken for this program. The Director of the Princeton Plasma Physics Laboratory (PPPL) was asked by DOE to set up this national team structure, and the current senior management positions and delegated responsibilities reflect that approach. While reporting lines and delegated roles are clear in the organization chart for TPX, one way to view, it, different from that of the individuals responsible upward through this management structure for various elements of the project, is through institutional responsibilities to the senior management team. In this view the management team relies on several national laboratories, each using industry contracts for major sub-systems and components, to execute the project. These responsibilities for design and for contracting are listed, showing that all major contracts will come through three national laboratories, forming teams for their responsible activities.

  17. Divertor design for the tokamak physics experiment

    NASA Astrophysics Data System (ADS)

    Hill, D. N.; Braams, B.; Brooks, J. N.; Ruzic, D. N.; Ulrickson, M.; Werley, K. A.; Campbell, R.; Goldston, R.; Kaiser, T.; Neilson, G. H.; Mioduszewski, P.; Rensink, M. E.; Rognlien, T. D.

    1995-04-01

    In this paper we discuss the divertor design for the planned TPX tokamak, which will explore the physics and technology of steady state (1000 s pulses) heat and particle removal in high confinement (up to 4 × L-mode), high beta (up to βN = 5) divertor plasmas sustained by non-inductive current drive. TPX will operate in the double-null divertor configuration, with actively cooled graphite targets forming a deep (0.57 m) slot at the outer strike point. The peak heat flux on the highly tilted (74° from normal) re-entrant divertor plate (tilted to recycle ions back toward the separatrix) will be in the range of 4-6 MW/m 2 with 17.5 MW of auxiliary heating power. The combination of pumping and gas puffing (D 2 plus impurities), along with higher heating power (45 MW maximum) will allow testing of radiative divertor concepts at ITER-like power densities.

  18. Divertor design for the Tokamak Physics Experiment

    NASA Astrophysics Data System (ADS)

    Hill, D. N.; Braams, B.; Brooks, J. N.; Ruzic, D. N.; Ulrickson, M.; Werley, K. A.; Campbell, R.; Goldston, R.; Kaiser, T.; Nellson, G. H.

    1994-05-01

    In this paper we discuss the present divertor design for the planned TPX tokamak, which will explore the physics and technology of steady-state (1000s pulses) heat and particle removal in high confinement (2-4 x L-mode), high beta (beta(sub N) greater than or equal to 3) divertor plasmas sustained by non-induct ive current drive. The TPX device will operate in the double-null divertor configuration, with actively cooled graphite targets forming a deep (0.5 m) slot at the outer strike point. The peak heat flux on, the highly tilted (74 deg) from normal) re-entrant (to recycle ions back toward the separatrix) will be in the range of 4-6 MW/sq m with 18 MW of neutral beams and RF heating power. The combination of active pumping and gas puffing (deuterium plus impurities), along with higher heating power (45 MW maximum) will allow testing of radiative divertor concepts at ITER-like power densities.

  19. Nonlinear fishbone dynamics in spherical tokamaks

    SciTech Connect

    Wang, Feng; Fu, G. Y.; Shen, Wei

    2016-11-22

    Linear and nonlinear kinetic-MHD hybrid simulations have been carried out to investigate linear stability and nonlinear dynamics of beam-driven fishbone instability in spherical tokamak plasmas. Realistic NSTX parameters with finite toroidal rotation were used. Our results show that the fishbone is driven by both trapped and passing particles. The instability drive of passing particles is comparable to that of trapped particles in the linear regime. The effects of rotation are destabilizing and a new region of instability appears at higher q min (>1.5) values, q min being the minimum of safety factor profile. In the nonlinear regime, the mode saturates due to flattening of beam ion distribution, and this persists after initial saturation while mode frequency chirps down in such a way that the resonant trapped particles move out radially and keep in resonance with the mode. Correspondingly, the flattening region of beam ion distribution expands radially outward. Furthermore, a substantial fraction of initially non-resonant trapped particles become resonant around the time of mode saturation and keep in resonance with the mode as frequency chirps down. On the other hand, the fraction of resonant passing particles is significantly smaller than that of trapped particles. Finally, our analysis shows that trapped particles provide the main drive to the mode in the nonlinear regime.

  20. Nonlinear fishbone dynamics in spherical tokamaks

    SciTech Connect

    Wang, Feng; Fu, G.Y.; Shen, Wei

    2017-01-01

    Linear and nonlinear kinetic-MHD hybrid simulations have been carried out to investigate linear stability and nonlinear dynamics of beam-driven fishbone instability in spherical tokamak plasmas. Realistic NSTX parameters with finite toroidal rotation were used. The results show that the fishbone is driven by both trapped and passing particles. The instability drive of passing particles is comparable to that of trapped particles in the linear regime. The effects of rotation are destabilizing and a new region of instability appears at higher q min (>1.5) values, q min being the minimum of safety factor profile. In the nonlinear regime, the mode saturates due to flattening of beam ion distribution, and this persists after initial saturation while mode frequency chirps down in such a way that the resonant trapped particles move out radially and keep in resonance with the mode. Correspondingly, the flattening region of beam ion distribution expands radially outward. A substantial fraction of initially non-resonant trapped particles become resonant around the time of mode saturation and keep in resonance with the mode as frequency chirps down. On the other hand, the fraction of resonant passing particles is significantly smaller than that of trapped particles. Our analysis shows that trapped particles provide the main drive to the mode in the nonlinear regime.

  1. Nonlinear fishbone dynamics in spherical tokamaks

    DOE PAGES

    Wang, Feng; Fu, G. Y.; Shen, Wei

    2016-11-22

    Linear and nonlinear kinetic-MHD hybrid simulations have been carried out to investigate linear stability and nonlinear dynamics of beam-driven fishbone instability in spherical tokamak plasmas. Realistic NSTX parameters with finite toroidal rotation were used. Our results show that the fishbone is driven by both trapped and passing particles. The instability drive of passing particles is comparable to that of trapped particles in the linear regime. The effects of rotation are destabilizing and a new region of instability appears at higher q min (>1.5) values, q min being the minimum of safety factor profile. In the nonlinear regime, the mode saturatesmore » due to flattening of beam ion distribution, and this persists after initial saturation while mode frequency chirps down in such a way that the resonant trapped particles move out radially and keep in resonance with the mode. Correspondingly, the flattening region of beam ion distribution expands radially outward. Furthermore, a substantial fraction of initially non-resonant trapped particles become resonant around the time of mode saturation and keep in resonance with the mode as frequency chirps down. On the other hand, the fraction of resonant passing particles is significantly smaller than that of trapped particles. Finally, our analysis shows that trapped particles provide the main drive to the mode in the nonlinear regime.« less

  2. Zonal flows in tokamaks with anisotropic pressure

    NASA Astrophysics Data System (ADS)

    Ren, Haijun

    2014-04-01

    Zonal flows (ZFs) in a tokamak plasma with anisotropic pressure are investigated. The dynamics of perpendicular and parallel pressures are determined by the Chew-Goldberger-Low double equations and low-β condition is adopted, where β is the ratio of plasma pressure to the magnetic field pressure. The dispersion relation is analytically derived and illustrates two branches of ZFs. The low frequency zonal flow (LFZF) branch becomes unstable when χ, the ratio of the perpendicular pressure to the parallel one, is greater than a threshold value χc, which is about 3.8. In the stable region, its frequency increases first and then decreases with increasing χ. For χ = 1, the frequency of LFZF agrees well with the experimental observation. For the instability, the growth rate of LFZF increases with χ. The geodesic acoustic mode branch is shown to be always stable with a frequency increasing with χ. The safety factor is shown to diminish the frequencies of both branches or the growth rate of LFZF.

  3. Sensitivity of predictive tokamak plasma transport simulations

    SciTech Connect

    Redd, A.J.; Kritz, A.H.; Bateman, G.; Kinsey, J.E.

    1997-06-01

    The sensitivity of our time-dependent simulations of low confinement (L-mode) discharges to variations in initial profiles and time-dependent boundary conditions has been explored. These time-dependent tokamak plasma simulations were performed using a theory-based Multi-mode transport model that includes ion temperature gradient (ITG) and trapped electron modes (TEM), kinetic and resistive ballooning modes and neoclassical modes. The density and temperature profiles predicted in our simulations of L-mode discharges are found to be robust, even with significant variations in the initial or boundary conditions. Although transport associated with a single mode can be strongly affected by local changes in plasma parameters resulting from changes in the boundary conditions, the total transport remains largely unchanged because of compensation by other transport modes. The sensitivity of the predicted temperature and density profiles to a variation in the Multi-mode model is also examined. When the Dominguez-Waltz theory of transport driven by ITG and TEM modes is replaced in the Multi-mode model by the Weiland description, we find that the predictions of the Weiland model more closely match the experimental data. {copyright} {ital 1997 American Institute of Physics.}

  4. Tokamak power system studies at ANL

    SciTech Connect

    Baker, C.C.; Ehst, D.A.; Brooks, J.N.; Evans, K. Jr.

    1986-06-01

    The following features, in particular, have been examined: (a) large aspect ratio (A approx. = 6), which may ease maintenance; (b) high beta (..beta.. greater than or equal to 0.20) without indentation, which brings the maximum toroidal field down to about 6 to 7 T; (c) low toroidal current (I approx. = 4MA), which reduces the cost of the current drive and equilibrium field system; and (d) steady state operation with current density control via fast and slow wave current drive. The key to high beta operation with low toroidal current lies in utilizing second stability regime equilibria with the required current distributions produced by an appropriate selection of wave driver frequencies and power spectra. The ray tracing and current drive calculation is self-consistent with the actual magnetic fields they produce in the plasma. The impurity control activities in TPSS have emphasized the self-pumping concept as applied to using the entire first wall or ''slot'' limiters. The blanket design effort has emphasized liquid metal and Flibe concepts. The reference concept is a liquid lithium/vanadium, self-cooled configuration. Overall, there exists a number of major design improvements which will substantially improve the attractiveness of tokamak reactors.

  5. A cross-tokamak neural network disruption predictor for the JET and ASDEX Upgrade tokamaks

    NASA Astrophysics Data System (ADS)

    Windsor, C. G.; Pautasso, G.; Tichmann, C.; Buttery, R. J.; Hender, T. C.; EFDA Contributors, JET; ASDEX Upgrade Team

    2005-05-01

    First results are reported on the prediction of disruptions in one tokamak, based on neural networks trained on another tokamak. The studies use data from the JET and ASDEX Upgrade devices, with a neural network trained on just seven normalized plasma parameters. In this way, a simple single layer perceptron network trained solely on JET correctly anticipated 67% of disruptions on ASDEX Upgrade in advance of 0.01 s before the disruption. The converse test led to a 69% success rate in advance of 0.04 s before the disruption in JET. Only one overall time scaling parameter is allowed between the devices, which can be introduced from theoretical arguments. Disruption prediction performance based on such networks trained and tested on the same device shows even higher success rates (JET, 86%; ASDEX Upgrade, 90%), despite the small number of inputs used and simplicity of the network. It is found that while performance for networks trained and tested on the same device can be improved with more complex networks and many adjustable weights, for cross-machine testing the best approach is a simple single layer perceptron. This offers the basis of a potentially useful technique for large future devices such as ITER, which with further development might help to reduce disruption frequency and minimize the need for a large disruption campaign to train disruption avoidance systems.

  6. Development of frequency modulation reflectometer for Korea Superconducting Tokamak Advanced Research tokamak

    NASA Astrophysics Data System (ADS)

    Seo, Seong-Heon; Park, Jinhyung; Wi, H. M.; Lee, W. R.; Kim, H. S.; Lee, T. G.; Kim, Y. S.; Kang, Jin-Seob; Bog, M. G.; Yokota, Y.; Mase, A.

    2013-08-01

    Frequency modulation reflectometer has been developed to measure the plasma density profile of the Korea Superconducting Tokamak Advanced Research tokamak. Three reflectometers are operating in extraordinary polarization mode in the frequency range of Q band (33.6-54 GHz), V band (48-72 GHz), and W band (72-108 GHz) to measure the density up to 7 × 1019 m-3 when the toroidal magnetic field is 2 T on axis. The antenna is installed inside of the vacuum vessel. A new vacuum window is developed by using 50 μm thick mica film and 0.1 mm thick gold gasket. The filter bank of low pass filter, notch filter, and Faraday isolator is used to reject the electron cyclotron heating high power at attenuation of 60 dB. The full frequency band is swept in 20 μs. The mixer output is directly digitized with sampling rate of 100 MSamples/s. The phase is obtained by using wavelet transform. The whole hardware and software system is described in detail and the measured density profile is presented as a result.

  7. Development of frequency modulation reflectometer for Korea Superconducting Tokamak Advanced Research tokamak

    SciTech Connect

    Seo, Seong-Heon; Wi, H. M.; Lee, W. R.; Kim, H. S.; Lee, T. G.; Kim, Y. S.; Park, Jinhyung; Kang, Jin-Seob; Bog, M. G.; Yokota, Y.; Mase, A.

    2013-08-15

    Frequency modulation reflectometer has been developed to measure the plasma density profile of the Korea Superconducting Tokamak Advanced Research tokamak. Three reflectometers are operating in extraordinary polarization mode in the frequency range of Q band (33.6–54 GHz), V band (48–72 GHz), and W band (72–108 GHz) to measure the density up to 7 × 10{sup 19} m{sup −3} when the toroidal magnetic field is 2 T on axis. The antenna is installed inside of the vacuum vessel. A new vacuum window is developed by using 50 μm thick mica film and 0.1 mm thick gold gasket. The filter bank of low pass filter, notch filter, and Faraday isolator is used to reject the electron cyclotron heating high power at attenuation of 60 dB. The full frequency band is swept in 20 μs. The mixer output is directly digitized with sampling rate of 100 MSamples/s. The phase is obtained by using wavelet transform. The whole hardware and software system is described in detail and the measured density profile is presented as a result.

  8. Development of frequency modulation reflectometer for Korea Superconducting Tokamak Advanced Research tokamak.

    PubMed

    Seo, Seong-Heon; Park, Jinhyung; Wi, H M; Lee, W R; Kim, H S; Lee, T G; Kim, Y S; Kang, Jin-Seob; Bog, M G; Yokota, Y; Mase, A

    2013-08-01

    Frequency modulation reflectometer has been developed to measure the plasma density profile of the Korea Superconducting Tokamak Advanced Research tokamak. Three reflectometers are operating in extraordinary polarization mode in the frequency range of Q band (33.6-54 GHz), V band (48-72 GHz), and W band (72-108 GHz) to measure the density up to 7 × 10(19) m(-3) when the toroidal magnetic field is 2 T on axis. The antenna is installed inside of the vacuum vessel. A new vacuum window is developed by using 50 μm thick mica film and 0.1 mm thick gold gasket. The filter bank of low pass filter, notch filter, and Faraday isolator is used to reject the electron cyclotron heating high power at attenuation of 60 dB. The full frequency band is swept in 20 μs. The mixer output is directly digitized with sampling rate of 100 MSamples/s. The phase is obtained by using wavelet transform. The whole hardware and software system is described in detail and the measured density profile is presented as a result.

  9. Prospects for pilot plants based on the tokamak, spherical tokamak and stellarator

    NASA Astrophysics Data System (ADS)

    Menard, J. E.; Bromberg, L.; Brown, T.; Burgess, T.; Dix, D.; El-Guebaly, L.; Gerrity, T.; Goldston, R. J.; Hawryluk, R. J.; Kastner, R.; Kessel, C.; Malang, S.; Minervini, J.; Neilson, G. H.; Neumeyer, C. L.; Prager, S.; Sawan, M.; Sheffield, J.; Sternlieb, A.; Waganer, L.; Whyte, D.; Zarnstorff, M.

    2011-10-01

    A potentially attractive next-step towards fusion commercialization is a pilot plant, i.e. a device ultimately capable of small net electricity production in as compact a facility as possible and in a configuration scalable to a full-size power plant. A key capability for a pilot-plant programme is the production of high neutron fluence enabling fusion nuclear science and technology (FNST) research. It is found that for physics and technology assumptions between those assumed for ITER and nth-of-a-kind fusion power plant, it is possible to provide FNST-relevant neutron wall loading in pilot devices. Thus, it may be possible to utilize a single facility to perform FNST research utilizing reactor-relevant plasma, blanket, coil and auxiliary systems and maintenance schemes while also targeting net electricity production. In this paper three configurations for a pilot plant are considered: the advanced tokamak, spherical tokamak and compact stellarator. A range of configuration issues is considered including: radial build and blanket design, magnet systems, maintenance schemes, tritium consumption and self-sufficiency, physics scenarios and a brief assessment of research needs for the configurations.

  10. A method for determining poloidal coil configurations for tokamak devices

    SciTech Connect

    Evans, K. Jr.

    1990-12-01

    This paper presents a method for obtaining the locations and currents of the poloidal coil systems for a tokamak, given an desirable magnetohydrodynamic equilibrium for the device. The method involves a simultaneous minimization of the match to the desired poloidal field and the stored energy in the coils, subject to the constraints necessary to achieve decoupling of the equilibrium and inductive-current-drive (ohmic-heating) systems and to achieve a given coupling of the current-drive system with the plasma. A compendium of mutual and self-inductance formulas as they apply to tokamak systems is presented, as well as examples of how the method has been used in the design of several tokamaks. Finally, a user manual for a computer code that implements this method is provided. 14 refs., 11 figs., 1 tab.

  11. Runaway electrons in a tokamak: A free-electron maser

    SciTech Connect

    Kurzan, B.; Steuer, K.

    1997-04-01

    In ohmic divertor plasma discharges of the ASDEX upgrade tokamak containing a small population of runaway electrons, fluctuating emission in the microwave region with a very narrow bandwidth is observed. The radiation can be explained by relativistic runaway electrons, which are captured in a ripple resonance of the tokamak and are thus made monoenergetic enough that they can undergo the collective instability of a free-electron maser. From the frequency of the maser, the energy of the runaway electrons, and from the linewidth and energy per radiation pulse, the particle density of the runaway electrons is determined locally. Observing this maser radiation is thus a different diagnostic for runaway electrons in tokamaks. {copyright} {ital 1997} {ital The American Physical Society}

  12. Driven magnetic reconnection in the COMPASS-C tokamak

    SciTech Connect

    Morris, A.W.; Carolan, P.G.; Fitzpatrick, R.; Hender, T.C.; Todd, T.N. , Abingdon, Oxon )

    1992-02-01

    The question of the influence of nonaxisymmetric field perturbations on tokamaks is investigated. Recent experiments in the COMPASS-C tokamak (in {ital Proceedings} {ital of} {ital the} 15{ital th} {ital Symposium} {ital on} {ital Fusion} {ital Technology}, Utrecht (North-Holland, Amsterdam, 1989), Vol. 1, p. 361) with externally applied helical fields reveal that magnetic islands do not appear until the applied field exceeds a certain value, when plasma rotation and confinement are affected. A new resistive magnetohydrodynamic model including plasma rotation now provides an explanation of this threshold, and is quantitatively consistent with experimental results in Ohmic plasmas. The results indicate the tolerable error fields in future tokamaks. The effects of perturbations with various poloidal and toroidal mode numbers have been studied.

  13. Texas Experimental Tokamak. Technical progress report, April 1990--April 1993

    SciTech Connect

    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.

  14. Tokamak dust particle size and surface area measurement

    SciTech Connect

    Carmack, W.J.; Smolik, G.R.; Anderl, R.A.; Pawelko, R.J.; Hembree, P.B.

    1998-07-01

    The INEEL has analyzed a variety of dust samples from experimental tokamaks: General Atomics` DII-D, Massachusetts Institute of Technology`s Alcator CMOD, and Princeton`s TFTR. These dust samples were collected and analyzed because of the importance of dust to safety. The dust may contain tritium, be activated, be chemically toxic, and chemically reactive. The INEEL has carried out numerous characterization procedures on the samples yielding information useful both to tokamak designers and to safety researchers. Two different methods were used for particle characterization: optical microscopy (count based) and laser based volumetric diffraction (mass based). Surface area of the dust samples was measured using Brunauer, Emmett, and Teller, BET, a gas adsorption technique. The purpose of this paper is to present the correlation between the particle size measurements and the surface area measurements for tokamak dust.

  15. Prospects and status of low-aspect-ratio tokamaks

    SciTech Connect

    Peng, Y.K.M.

    1994-12-31

    The prospects for the low-aspect-ratio (A) tokamak to fulfill the requirements of viable fusion power plants are considered relative to the present status in data and modeling. Desirable physics and design features for an attractive Blanket Test Facility and power reactors are estimated for low-A tokamaks based on calculations improved with the latest data from small pioneering experiments. While these experiments have confirmed some of the recent predictions for low-A, they also identify the remaining issues that require verification before reliable projections can be made for these deuterium-tritium applications. The results show that the low-A regime of small size, modest field, and high current offers a path complementary to the standard and high A tokamaks in developing the full potential of fusion power.

  16. The engineering design of the Tokamak Physics Experiment (TPX)

    SciTech Connect

    Reiersen, W.T.

    1994-09-01

    The Tokamak Physics Experiment (TPX) is designed to develop the scientific basis for a compact and continuously operating tokamak fusion reactor. TPX has a long pulse (1000s) capability, can accommodate high divertor heat loads, has a flexible poloidal field (PF) system, and auxiliary heating and current drive systems that make it an ideal test bed for development of attractive reactor concepts. The design incorporates superconducting magnets in both the toroidal field (TF) and poloidal field (PF) systems. Long pulse deuterium operation will produce 6 {times} 10{sup 21} neutrons per year requiring remote maintenance of the in-vessel hardware. This paper provides an overview of the TPX design with the emphasis on developments in the tokamak design since the Conceptual Design Review (CDR) in March, 1993.

  17. Saturated internal instabilities in advanced-tokamak plasmas

    NASA Astrophysics Data System (ADS)

    Hua, M.-D.; Chapman, I. T.; Pinches, S. D.; Hastie, R. J.; MAST Team

    2010-06-01

    "Advanced tokamak" (AT) scenarios were developed with the aim of reaching steady-state operation in future potential tokamak fusion power plants. AT scenarios exhibit non-monotonic to flat safety factor profiles (q, a measure of the magnetic field line pitch), with the minimum q (qmin) slightly above an integer value (qs). However, it has been predicted that these q profiles are unstable to ideal magnetohydrodynamic instabilities as qmin approaches qs. These ideal instabilities, observed and diagnosed as such for the first time in MAST plasmas with AT-like q profiles, have far-reaching consequences like confinement degradation, flattening of the toroidal core rotation or enhanced fast ion losses. These observations motivate the stability analysis of advanced-tokamak plasmas, with a view to provide guidance for stability thresholds in AT scenarios. Additionally, the measured rotation damping is compared to the self-consistently calculated predictions from neoclassical toroidal viscosity theory.

  18. Stochastic modeling of plasma mode forecasting in tokamak

    NASA Astrophysics Data System (ADS)

    Saadat, Sh.; Salem, M.; Ghoranneviss, M.; Khorshid, P.

    2012-04-01

    The structure of magnetohydrodynamic (MHD) modes has always been an interesting study in tokamaks. The mode number of tokamak plasma is the most important parameter, which plays a vital role in MHD instabilities. If it could be predicted, then the time of exerting external fields, such as feedback fields and Resonance Helical Field, could be obtained. Autoregressive Integrated Moving Average (ARIMA) and Seasonal Autoregressive Integrated Moving Average are useful models to predict stochastic processes. In this paper, we suggest using ARIMA model to forecast mode number. The ARIMA model shows correct mode number (m = 4) about 0.5 ms in IR-T1 tokamak and equations of Mirnov coil fluctuations are obtained. It is found that the recursive estimates of the ARIMA model parameters change as the plasma mode changes. A discriminator function has been proposed to determine plasma mode based on the recursive estimates of model parameters.

  19. Bootstrap currents in radio-frequency-driven tokamak equilibria

    SciTech Connect

    Hsiao, Ming-Yuan; Ehst, D.A.; Evans, K. Jr.

    1988-05-01

    Interest in the bootstrap current arising from neoclassical transport in tokamaks has increased recently in view of certain experimental observations. In this study, the bootstrap current is calculated for a number of rf current-driven tokamaks. Two-dimensional, self-consistent, steady-state tokamak MHD equilibria are obtained by including both the transport-driven bootstrap current and the externally driven rf current. The self-consistency is acomplished by iterating between two-dimensional MHD equilibrium calculations and the current calculations (including bootstrap and rf ray-tracing). Calculations for other reactor parameters of interest are also carried out. It is found that for reactor-grade plasmas, the bootstrap current contribution to the toroidal current is, in general, important. An approxiamte scaling law for GAMMA, based on parametric survey performed, is also obtained. 16 refs., 8 figs., 1 tab.

  20. Hybrid Method for Tokamak MHD Equilibrium Configuration Reconstruction

    NASA Astrophysics Data System (ADS)

    He, Hong-Da; Dong, Jia-Qi; Zhang, Jin-Hua; Jiang, Hai-Bin

    2007-02-01

    A hybrid method for tokamak MHD equilibrium configuration reconstruction is proposed and employed in the modified EFIT code. This method uses the free boundary tokamak equilibrium configuration reconstruction algorithm with one boundary point fixed. The results show that the position of the fixed point has explicit effects on the reconstructed divertor configurations. In particular, the separatrix of the reconstructed divertor configuration precisely passes the required position when the hybrid method is used in the reconstruction. The profiles of plasma parameters such as pressure and safety factor for reconstructed HL-2A tokamak configurations with the hybrid and the free boundary methods are compared. The possibility for applications of the method to swing the separatrix strike point on the divertor target plate is discussed.

  1. Ripple-induced energetic particle loss in tokamaks

    NASA Astrophysics Data System (ADS)

    White, R. B.; Goldston, R. J.; Redi, M. H.; Budny, R. V.

    1996-08-01

    The threshold for stochastic transport of high energy trapped particles in a tokamak due to toroidal field ripple is calculated by explicit construction of primary resonances, and a numerical examination of the route to chaos. Critical field ripple amplitude is determined for loss. The expression is given in magnetic coordinates and makes no assumptions regarding shape or up-down symmetry. An algorithm is developed including the effects of prompt axisymmetic orbit loss, ripple trapping, convective banana flow, and stochastic ripple loss, which gives accurate ripple loss predictions for representative Tokamak Fusion Test Reactor [R. Hawryluk, Plasma Phys. Controlled Fusion 33, 1509 (1991)] and International Thermonuclear Experimental Reactor [K. Tomabechi, Proceedings of the 12th International Conference on Plasma Physics and Controlled Nuclear Fusion Research (International Atomic Energy Agency, Vienna, 1989), Vol. 3, p. 214] equilibria. The algorithm is extended to include the effects of collisions and drag, allowing rapid estimation of alpha particle loss in tokamaks.

  2. Fusion Plasma Theory: Task 3, Auxiliary radiofrequency heating of tokamaks

    SciTech Connect

    Scharer, J.E.

    1992-01-01

    The research performed under this grant during the past year has been concentrated on the following several key tokamak ICRF (Ion Cyclotron Range of Frequencies) coupling, heating and current drive issues: Efficient coupling during the L- to H- mode transition by analysis and computer simulation of ICRF antennas; analysis of ICRF cavity-backed coil antenna coupling to plasma edge profiles including fast and ion Bernstein wave coupling for heating and current drive; benchmarking the codes to compare with current JET, D-IIID and ASDEX experimental results and predictions for advanced tokamaks such as BPX and SSAT (Steady-State Advanced Tokamak); ICRF full-wave field solutions, power conservation, heating analyses and minority ion current drive; and the effects of fusion alpha particle or ion tail populations on the ICRF absorption. Research progress, publications, and conference and workshop presentations are summarized in this report.

  3. The Dynamic Mutation Characteristics of Thermonuclear Reaction in Tokamak

    PubMed Central

    Li, Jing; Quan, Tingting; Zhang, Wei; Deng, Wei

    2014-01-01

    The stability and bifurcations of multiple limit cycles for the physical model of thermonuclear reaction in Tokamak are investigated in this paper. The one-dimensional Ginzburg-Landau type perturbed diffusion equations for the density of the plasma and the radial electric field near the plasma edge in Tokamak are established. First, the equations are transformed to the average equations with the method of multiple scales and the average equations turn to be a Z2-symmetric perturbed polynomial Hamiltonian system of degree 5. Then, with the bifurcations theory and method of detection function, the qualitative behavior of the unperturbed system and the number of the limit cycles of the perturbed system for certain groups of parameter are analyzed. At last, the stability of the limit cycles is studied and the physical meaning of Tokamak equations under these parameter groups is given. PMID:24892099

  4. The dynamic mutation characteristics of thermonuclear reaction in Tokamak.

    PubMed

    Li, Jing; Quan, Tingting; Zhang, Wei; Deng, Wei

    2014-01-01

    The stability and bifurcations of multiple limit cycles for the physical model of thermonuclear reaction in Tokamak are investigated in this paper. The one-dimensional Ginzburg-Landau type perturbed diffusion equations for the density of the plasma and the radial electric field near the plasma edge in Tokamak are established. First, the equations are transformed to the average equations with the method of multiple scales and the average equations turn to be a Z 2-symmetric perturbed polynomial Hamiltonian system of degree 5. Then, with the bifurcations theory and method of detection function, the qualitative behavior of the unperturbed system and the number of the limit cycles of the perturbed system for certain groups of parameter are analyzed. At last, the stability of the limit cycles is studied and the physical meaning of Tokamak equations under these parameter groups is given.

  5. Joint Experiments on the Tokamaks CASTOR and T-10

    SciTech Connect

    Oost, G. van; Peleman, P.; Gryaznevich, M.; Malaquias, A.; Mank, G.; Berta, M.; Brotankova, J.; Dejarnac, R.; Dufkova, E.; Duran, I.; Hron, M.; Sentkerestiova, J.; Stoeckel, J.; Weinzettl, V.; Zajac, J.; Budaev, V.

    2008-04-07

    Small tokamaks may significantly contribute to the better understanding of phenomena in a wide range of fields such as plasma confiement and energy transport; plasma stability in different magnetic configurations; plasma turbulence and its impact on local and global plasma parameters; processes at the plasma edge and plasma-wall interaction; scenarios of additional heating and non-inductive current drive; new methods of plasma profile and parameter control; development of novel plasma diagnostics; benchmarking of new numerical codes and so on. Furthermore, due to the compactness, flexibility, low operation costs and high skill of their personnel small tokamaks are very convenient to develop and test new materials and technologies. Small tokamaks are suitable and important for broad international cooperation, providing the necessary environment and manpower to conduct dedicated joint research programmes. In addition, the experimental work on small tokamaks is very appropriate for the education of students, scientific activities of post-graduate students and for the training of personnel for large tokamaks. The first Joint (Host Laboratory) Experiment (JE1) has been carried out in 2005 on the CASTOR tokamak at the IPP Prague, Czech Republic. It was jointly organized by the IPP-ASCR and KFKI HAC, Budapest, involved 20 scientists from 7 countries and was supported through the IAEA and the ICTP, Trieste. The objective of JE1 was to perform studies of plasma edge turbulence and plasma confinement. Following the success of JE1, JE2 has been performed on T-10 at RRC 'Kurchatov Institute' in Moscow; 30 scientists from 13 countries participated in this experiment. This experiment aimed to continue JE1 turbulence studies, now extending them to the plasma core. Results of JE1 and JE2 will be overviewed and compared.

  6. Fractal structure of films deposited in a tokamak

    SciTech Connect

    Budaev, V. P.; Khimchenko, L. N.

    2007-04-15

    The surface of amorphous films deposited in the T-10 tokamak was studied in a scanning tunnel microscope. The surface relief on a scale from 10 nm to 100 {mu}m showed a stochastic surface topography and revealed a hierarchy of grains. The observed variety of irregular structures of the films was studied within the framework of the concept of scale invariance using the methods of fractal geometry and statistical physics. The experimental probability density distribution functions of the surface height variations are close in shape to the Cauchy distribution. The stochastic surface topography of the films is characterized by a Hurst parameter of H = 0.68-0.85, which is evidence of a nontrivial self-similarity of the film structure. The fractal character and porous structure of deposited irregular films must be considered as an important issue related to the accumulation of tritium in the ITER project. The process of film growth on the surface of tokamak components exposed to plasma has been treated within the framework of the general concept of inhomogeneous surface growth. A strong turbulence of the edge plasma in tokamaks can give rise to fluctuations in the incident flux of particles, which leads to the growth of fractal films with grain dimensions ranging from nano-to micrometer scale. The shape of the surface of some films found in the T-10 tokamak has been interpreted using a model of diffusion-limited aggregation (DLA). The growth of films according to the discrete DLA model was simulated using statistics of fluctuations observed in a turbulent edge plasma of the T-10 tokamak. The modified DLA model reproduces well the main features of the surface of some films deposited in tokamaks.

  7. A self-consistent model of an isothermal tokamak

    NASA Astrophysics Data System (ADS)

    McNamara, Steven; Lilley, Matthew

    2014-10-01

    Continued progress in liquid lithium coating technologies have made the development of a beam driven tokamak with minimal edge recycling a feasibly possibility. Such devices are characterised by improved confinement due to their inherent stability and the suppression of thermal conduction. Particle and energy confinement become intrinsically linked and the plasma thermal energy content is governed by the injected beam. A self-consistent model of a purely beam fuelled isothermal tokamak is presented, including calculations of the density profile, bulk species temperature ratios and the fusion output. Stability considerations constrain the operating parameters and regions of stable operation are identified and their suitability to potential reactor applications discussed.

  8. DIII-D tokamak long range plan. Revision 3

    SciTech Connect

    1992-08-01

    The DIII-D Tokamak Long Range Plan for controlled thermonuclear magnetic fusion research will be carried out with broad national and international participation. The plan covers: (1) operation of the DIII-D tokamak to conduct research experiments to address needs of the US Magnetic Fusion Program; (2) facility modifications to allow these new experiments to be conducted; and (3) collaborations with other laboratories to integrate DIII-D research into the national and international fusion programs. The period covered by this plan is 1 November 19983 through 31 October 1998.

  9. Accessibility of second regions of stability in tokamaks

    SciTech Connect

    Manickam, J.

    1985-12-01

    Second regions of stability to the ideal ballooning modes have been shown to exist in large-aspect-ratio circular and small-aspect-ratio bean-shaped tokamaks. We report on the existence of these second stability regions in finite-aspect-ratio dee-shaped tokamaks. We also report on the discovery of a second-stable region with respect to the n = 1 external kink mode in a bean-shaped plasma. The role of the shear and current profile in determining these regions of parameter space are discussed. 13 refs., 6 figs.

  10. TIBER: Tokamak Ignition/Burn Experimental Research. Final design report

    SciTech Connect

    Henning, C.D.; Logan, B.G.; Barr, W.L.; Bulmer, R.H.; Doggett, J.N.; Johnson, B.M.; Lee, J.D.; Hoard, R.W.; Miller, J.R.; Slack, D.S.

    1985-11-01

    The Tokamak Ignition/Burn Experimental Research (TIBER) device is the smallest superconductivity tokamak designed to date. In the design plasma shaping is used to achieve a high plasma beta. Neutron shielding is minimized to achieve the desired small device size, but the superconducting magnets must be shielded sufficiently to reduce the neutron heat load and the gamma-ray dose to various components of the device. Specifications of the plasma-shaping coil, the shielding, coaling, requirements, and heating modes are given. 61 refs., 92 figs., 30 tabs. (WRF)

  11. Current Status and Future Technical Challenges for Tokamak Magnets

    SciTech Connect

    Martovetsky, N; Minervini, J; Okuno, K; Salpiero, E; Filatov, O

    2002-11-11

    Magnet technology for fusion in the last decade has been focusing mostly on the development of magnets for tokamaks--the most advanced fusion concept at the moment. The largest and the most complex tokamak under development is ITER. To demonstrate adequate design approaches to large magnets for ITER and to develop industrial capabilities, two large model coils and three insert coils, all using full-scale conductor, were built and tested by the international collaboration during 1994-2002. The status of the magnet technology and directions of future developments are discussed in this paper.

  12. What is the fate of runaway positrons in tokamaks?

    DOE PAGES

    Liu, Jian; Qin, Hong; Fisch, Nathaniel J.; ...

    2014-06-19

    In this study, massive runaway positrons are generated by runaway electrons in tokamaks. The fate of these positrons encodes valuable information about the runaway dynamics. The phase space dynamics of a runaway position is investigated using a Lagrangian that incorporates the tokamak geometry, loop voltage, radiation and collisional effects. It is found numerically that runaway positrons will drift out of the plasma to annihilate on the first wall, with an in-plasma annihilation possibility less than 0.1%. The dynamics of runaway positrons provides signatures that can be observed as diagnostic tools.

  13. Fusion-product transport in axisymmetric tokamaks: losses and thermalization

    SciTech Connect

    Hively, L.M.

    1980-01-01

    High-energy fusion-product losses from an axisymmetric tokamak plasma are studied. Prompt-escape loss fluxes (i.e. prior to slowing down) are calculated including the non-separable dependence of flux as a function of poloidal angle and local angle-of-incidence at the first wall. Fusion-product (fp) thermalization and heating are calculated assuming classical slowing down. The present analytical model describes fast ion orbits and their distribution function in realistic, high-..beta.., non-circular tokamak equilibria. First-orbit losses, trapping effects, and slowing-down drifts are also treated.

  14. The role of spherical torus in clarifying tokamak physics

    SciTech Connect

    Morris, A. W.; Peng, Yueng Kay Martin

    1999-01-01

    The spherical tokamak (ST) provides a unique environment in which to perform complementary and exacting tests of the tokamak physics required for a burning plasma experiment of any aspect ratio, while also having the potential for long-term fusion applications in its own right. New experiments are coming on-line in the UK (MAST), USA (NSTX, Pegasus), Russia (Globus-M), Brazil (ETE) and elsewhere, and the status of these devices will be reported, along with newly-analysed data from START. Those physics issues where the ST provides an opportunity to remove degeneracy in the databases or clarify one s understanding will be emphasized.

  15. Steady state self-induced current in tokamak

    SciTech Connect

    Gott, Yu. V.; Yurchenko, E. I.

    2009-11-15

    A model, which may make it possible to self-consistently calculate the self-driven current in tokamaks taking into account asymmetry and bootstrap currents, is presented. It is shown that the described self-driven current can provide steady-state tokamak operation without the seed current produced with the help of additional methods. The total self-consistent, self-driven current does not depend on magnetic field magnitude and is proportional to the square root from plasma pressure. The experimental data obtained in the National Spherical Torus Experiment are satisfactorily described by this model.

  16. Resistive demountable toroidal-field coils for tokamak reactors

    SciTech Connect

    Jassby, D.L.; Jacobsen, R.A.; Kalnavarns, J.; Masson, L.S.; Sekot, J.P.

    1981-07-01

    Readily demountable TF (toroidal-field) coils allow complete access to the internal components of a tokamak reactor for maintenance of replacement. The requirement of readily demountable joints dictates the use of water-cooled resistive coils, which have a host of decisive advantages over superconducting coils. Previous papers have shown that resistive TF coils for tokamak reactors can operate in the steady state with acceptable power dissipation (typically, 175 to 300 MW). This paper summarizes results of parametric studies of size optimization of rectangular TF coils and of a finite-element stress analysis, and examines several candidate methods of implementing demountable joints for rectangular coils constructed of plate segments.

  17. Adaptive grid finite element model of the tokamak scrapeoff layer

    SciTech Connect

    Kuprat, A.P.; Glasser, A.H.

    1995-07-01

    The authors discuss unstructured grids for application to transport in the tokamak edge SOL. They have developed a new metric with which to judge element elongation and resolution requirements. Using this method, the authors apply a standard moving finite element technique to advance the SOL equations while inserting/deleting dynamically nodes that violate an elongation criterion. In a tokamak plasma, this method achieves a more uniform accuracy, and results in highly stretched triangular finite elements, except near separatrix X-point where transport is more isotropic.

  18. Kinetic Energy Principle And Neoclassical Toroidal Torque In Tokamaks

    SciTech Connect

    Jong-Kyu Park

    2011-11-07

    It is shown that when tokamaks are perturbed the kinetic energy principle is closely related to the neoclassical toroidal torque by the action invariance of particles. Especially when tokamaks are perturbed from scalar pressure equilibria, the imaginary part of the potential energy in the kinetic energy principle is equivalent to the toroidal torque by the Neoclassical Toroidal Viscosity (NTV). A unified description therefore should be made for both physics. It is also shown in this case that the potential energy operator can be self-adjoint and thus the stability calculation can be simplified by minimizing the potential energy

  19. Internal Magnetic Configuration Measured by ECE Imaging on EAST Tokamak

    NASA Astrophysics Data System (ADS)

    Xu, Ming; Wen, Yizhi; Xie, Jinlin; Yu, Changxuan; Gao, Bingxi; Xu, Xiaoyuan; Liu, Wandong; Hu, Liqun; Sun, Youwen; Qian, Jinping; Wan, Baonian

    2013-12-01

    ECE imaging (electron cyclotron emission imaging) is an important diagnostic which can give 2D imaging of temperature fluctuation in the core of tokamak. A method based on ECE imaging is introduced which can give the information of the position of magnetic axis and the structure of internal magnetic surface for EAST tokamak. The EFIT equilibrium reconstruction is not reliable due to the absence of important core diagnostic at the initial phase for EAST, so the information given by ECE imaging could help to improve the accuracy of EFIT equilibrium reconstruction.

  20. Resonant-cavity ICRF coupler for large tokamaks

    SciTech Connect

    Perkins, F.W.; Kluge, R.F.

    1983-04-01

    A new resonant-cavity ICRF coupler is proposed for large tokamaks. The design features a novel resonant cavity, an rf magnetic-field orientation that effectively radiates fast Alfven waves, matching to 40 ..cap omega.. transmission lines, and an electric-field orientation so that the strongest rf electric fields are orthogonal to the main toroidal magnetic field thereby benefitting from magnetic insulation. As a result, the power handling capability is excellent. For the case of the Big-Dee Doublet III tokamak, a single 35 cm x 50 cm coupler can launch 20 MW of fast Alfven waves. Extrapolation to fusion reactor parameters is straightforward.