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Sample records for ht-2 tokamak

  1. Plasma discharge in ferritic first wall vacuum vessel of the Hitachi Tokamak HT-2

    International Nuclear Information System (INIS)

    Abe, Mitsushi; Nakayama, Takeshi; Asano, Katsuhiko; Otsuka, Michio

    1997-01-01

    A tokamak discharge with ferritic material first wall was tried successfully. The Hitachi Tokamak HT-2 had a stainless steel SUS304 vacuum vessel and modified to have a ferritic plate first wall for experiments to investigate the possibility of ferritic material usage in magnetic fusion devices. The achieved vacuum pressure and times used for discharge cleaning was roughly identical with the stainless steel first wall or the original HT-2. We concluded that ferritic material vacuum vessel is possible for tokamaks. (author)

  2. Characteristics of disruptive plasma current decay in the HT-2 tokamak

    International Nuclear Information System (INIS)

    Abe, Mitsushi; Takeuchi, Kazuhiro; Otsuka, Michio

    1993-01-01

    Motions of plasma current channel and time evolutions of eddy current distribution on the vacuum vessel during disruptive plasma current decay were studied experimentally in the Hitachi tokamak HT-2. The plasmas are vertically elongated and circularly shaped plasmas. A disruptive plasma current decay has three phases. During the first phase, a large displacement of the plasma position without plasma current decay is observed. Rapid plasma current decay is observed during the second phase and the decay rate is roughly constant with time. The eddy current distribution is like that due to the shell effect which creates a poloidal field to reduce the plasma displacement. During the third phase, the plasma current decays exponentially. The second phase is observed in slightly elongated and high plasma current (> 20 kA) circularly shaped plasmas. The plasma current decay rates in the second phase depend on the plasma cross sectional shape, but they do not in the third phase. The magnetic axis moves from the plasma area to the vacuum vessel wall between the second and third phases. (author)

  3. Magnetic analysis including the field due to vacuum vessel eddy currents in the Hitachi Tokamak (HT-2)

    International Nuclear Information System (INIS)

    Abe, Mitsushi; Takeuchi, Kazuhiro; Fukumoto, Hideshi; Otsuka, Michio

    1989-01-01

    A magnetic analysis to determine plasma surface position is applied to the magnetic data of the Hitachi Tokamak (HT-2). The analysis takes account of toroidal eddy currents on the vacuum vessel wall. Magnetic probes in HT-2 are placed on both sides of the wall (plasma side and outside), making it possible to determine magnitudes of eddy currents which flow in the toroidal direction. The magnitudes of the coil currents and eddy currents are determined so as to reproduce the measured magnetic fields, and to reconstruct flux surfaces and plasma surface are reconstructed. Taking into account the eddy currents, the determination errors of the plasma surface position are reduced by up to 1/2.3 during start-up and terminating phases, compared with the case without eddy currents. (author)

  4. Tokamak

    International Nuclear Information System (INIS)

    Wesson, John.

    1996-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Malgorzata S. Martin-Gronert

    2016-04-01

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

  6. 5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats.

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Darya V. Bazovkina

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2014-01-03

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

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

    Science.gov (United States)

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

    2016-02-01

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

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

    International Nuclear Information System (INIS)

    Nonogaki, Katsunori; Nozue, Kana; Oka, Yoshitomo

    2006-01-01

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

  12. Activation of glucocorticoid receptors increases 5-HT2A receptor levels

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Kirkegaard, Lisbeth; Krey, Gesa

    2009-01-01

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

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

    Science.gov (United States)

    Diaz, Silvina Laura; Maroteaux, Luc

    2011-09-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    OpenAIRE

    2010-01-01

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

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

    International Nuclear Information System (INIS)

    Busatto, G.F.

    1996-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Henri O. Arola

    2017-04-01

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

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

    Science.gov (United States)

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

    2016-11-10

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

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

    Directory of Open Access Journals (Sweden)

    Markus Thamm

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

  20. 5HT2A receptor blockade in dorsomedial striatum reduces repetitive behaviors in BTBR mice.

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2018-02-27

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

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

    Science.gov (United States)

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

    2016-08-20

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-05-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wolfgang Blenau

    2017-05-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  11. Current radiosynthesis strategies for 5-HT2A receptor PET tracers

    DEFF Research Database (Denmark)

    Herth, Matthias M; Knudsen, Gitte M

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Twum eAnsah

    2011-06-01

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

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

    Science.gov (United States)

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

    2017-10-01

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

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

    International Nuclear Information System (INIS)

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

    1998-01-01

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

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Guan Kunliang

    2003-06-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2001-08-01

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

  2. 5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology

    DEFF Research Database (Denmark)

    Peng, Yao; Mccorvy, John D.; Harpsøe, Kasper

    2018-01-01

    Drugs frequently require interactions with multiple targets—via a process known as polypharmacology—to achieve their therapeutic actions. Currently, drugs targeting several serotonin receptors, including the 5-HT2C receptor, are useful for treating obesity, drug abuse, and schizophrenia. The comp...... the structural basis of polypharmacology at canonical GPCRs and illustrates how understanding characteristic patterns of ligand-receptor interaction and activation may ultimately facilitate drug design at multiple GPCRs....

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

    Directory of Open Access Journals (Sweden)

    Drew J. Puxty

    2017-07-01

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

  4. The 5-HT2A receptor binding pattern in the human brain is strongly genetically determined

    DEFF Research Database (Denmark)

    Pinborg, Lars H; Arfan, Haroon; Haugbol, Steven

    2007-01-01

    With the appropriate radiolabeled tracers, positron emission tomography (PET) enables in vivo human brain imaging of markers for neurotransmission, including neurotransmitter synthesis, receptors, and transporters. Whereas structural imaging studies have provided compelling evidence that the human...... brain anatomy is largely genetically determined, it is currently unknown to what degree neuromodulatory markers are subjected to genetic and environmental influence. Changes in serotonin 2A (5-HT(2A)) receptors have been reported to occur in various neuropsychiatric disorders and an association between...

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

    Science.gov (United States)

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

    2015-01-01

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

  6. 5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease

    OpenAIRE

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2011-04-01

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

  10. Continuous tokamaks

    International Nuclear Information System (INIS)

    Peng, Y.K.M.

    1978-04-01

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

  11. Tokamak experiments

    International Nuclear Information System (INIS)

    Robinson, D.C.

    1987-01-01

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

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

    Science.gov (United States)

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

    2010-11-11

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

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

    DEFF Research Database (Denmark)

    Ettrup, Anders; Palner, Mikael; Gillings, Nic

    2010-01-01

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

  14. 5-HT2A Serotonin Receptor Density in Adult Male Rats’ Hippocampus after Morphine-based Conditioned Place Preference

    Directory of Open Access Journals (Sweden)

    Rabie Mohammadi

    2016-07-01

    Conclusion: We concluded that the phenomenon of conditioned place preference induced by morphine can cause a significant increase in the number of serotonin 5-HT2A receptors in neurons of all areas of hippocampus.

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

    Science.gov (United States)

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

    2010-10-01

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

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

    Science.gov (United States)

    Nair, Sunila G; Gudelsky, Gary A

    2004-09-15

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

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

    OpenAIRE

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

    2014-01-01

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

  18. 5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease.

    Science.gov (United States)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    Science.gov (United States)

    Banks, Matthew L; Negus, S Stevens

    2017-04-01

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

  2. 5-HT2A receptor deficiency alters the metabolic and transcriptional, but not the behavioral, consequences of chronic unpredictable stress

    Directory of Open Access Journals (Sweden)

    Minal Jaggar

    2017-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhao-hui Xu

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

    2001-01-01

    Aim: The characteristics of 5HT 2 receptor binding were investigated in major depression in vivo using positron emission tomography and the radioligand F-18-altanserin. Methods: Twelve patients from families with high loading of depression living in a geographically restricted region were examined and compared with normal control subjects. At the time of the PET measurement all patients were remitted; in some of them remission was sustained by antidepressive medication. Binding potential was assessed by Logan's graphical analysis method. Results: The binding of F-18-altanserin was about 38% lower in patients than in healthy controls (p 2 receptors are altered in depression. We present evidence for a reduction of the receptor density, which might be usable as trait marker of subjects susceptible for depressive illness. (orig.) [de

  8. 4-(Phenylsulfonyl)piperidines: novel, selective, and bioavailable 5-HT(2A) receptor antagonists.

    Science.gov (United States)

    Fletcher, Stephen R; Burkamp, Frank; Blurton, Peter; Cheng, Susan K F; Clarkson, Robert; O'Connor, Desmond; Spinks, Daniel; Tudge, Matthew; van Niel, Monique B; Patel, Smita; Chapman, Kerry; Marwood, Rose; Shepheard, Sara; Bentley, Graham; Cook, Gina P; Bristow, Linda J; Castro, Jose L; Hutson, Peter H; MacLeod, Angus M

    2002-01-17

    On the basis of a spirocyclic ether screening lead, a series of acyclic sulfones have been identified as high-affinity, selective 5-HT(2A) receptor antagonists. Bioavailability lacking in the parent, 1-(2-(2,4-difluorophenyl)ethyl)-4-(phenylsulfonyl)piperidine (12), was introduced by using stability toward rat liver microsomes as a predictor of bioavailability. By this means, the 4-cyano- and 4-carboxamidophenylsulfonyl derivatives 26 and 31 were identified as orally bioavailable, brain-penetrant analogues suitable for evaluation in animal models. Bioavailability was also attainable by N substitution leading to the N-phenacyl derivative 35. IKr activity detected through counterscreening was reduced to insignificant levels in vivo with the latter compound.

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

    Science.gov (United States)

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

    2014-01-03

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

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

    DEFF Research Database (Denmark)

    Ísberg, Vignir; Balle, Thomas; Sander, Tommy

    2011-01-01

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

  11. Tokamak COMPASS

    Czech Academy of Sciences Publication Activity Database

    Řípa, Milan; Křenek, Petr

    2011-01-01

    Roč. 17, č. 1 (2011), s. 32-34 ISSN 1210-4612 Institutional research plan: CEZ:AV0Z20430508 Keywords : fusion * tokamak * Compass * Golem * Institute of Plasma Physics AVCR v.v * NBI * diagnostics Subject RIV: BL - Plasma and Gas Discharge Physics

  12. Cortical and subcortical 5-HT2A receptor binding in neuroleptic-naive first-episode schizophrenic patients

    DEFF Research Database (Denmark)

    Erritzoe, David; Rasmussen, Hans; Kristiansen, Klaus Nyegaard

    2008-01-01

    MRIs and PET images. The cerebellum was used as a reference region. The binding potential of specific tracer binding (BP(p)) was used as the outcome measure. No significant difference was seen in cortical receptor distribution between patients and controls. An increase in 5-HT(2A) receptor binding...

  13. Acute social defeat does not alter cerebral 5-HT2A receptor binding in male Wistar rats

    DEFF Research Database (Denmark)

    Visser, Anniek K D; Meerlo, Peter; Ettrup, Anders

    2014-01-01

    suppressed growth, but did not affect anxiety-like behavior in an open field test. A positron emission tomography scan with the 5-HT2A R tracer [11C]MDL 100907 1 day and 3 weeks after defeat did not show significant changes in receptor binding. To verify these results, [3H]MDL 100907 binding assays were...

  14. Fingerprint-Based Machine Learning Approach to Identify Potent and Selective 5-HT2BR Ligands

    Directory of Open Access Journals (Sweden)

    Krzysztof Rataj

    2018-05-01

    Full Text Available The identification of subtype-selective GPCR (G-protein coupled receptor ligands is a challenging task. In this study, we developed a computational protocol to find compounds with 5-HT2BR versus 5-HT1BR selectivity. Our approach employs the hierarchical combination of machine learning methods, docking, and multiple scoring methods. First, we applied machine learning tools to filter a large database of druglike compounds by the new Neighbouring Substructures Fingerprint (NSFP. This two-dimensional fingerprint contains information on the connectivity of the substructural features of a compound. Preselected subsets of the database were then subjected to docking calculations. The main indicators of compounds’ selectivity were their different interactions with the secondary binding pockets of both target proteins, while binding modes within the orthosteric binding pocket were preserved. The combined methodology of ligand-based and structure-based methods was validated prospectively, resulting in the identification of hits with nanomolar affinity and ten-fold to ten thousand-fold selectivities.

  15. Stimulation of 5-HT2A receptors recovers sensory responsiveness in acute spinal neonatal rats.

    Science.gov (United States)

    Swann, Hillary E; Kauer, Sierra D; Allmond, Jacob T; Brumley, Michele R

    2017-02-01

    Quipazine is a 5-HT 2A -receptor agonist that has been used to induce motor activity and promote recovery of function after spinal cord injury in neonatal and adult rodents. Sensory stimulation also activates sensory and motor circuits and promotes recovery after spinal cord injury. In rats, tail pinching is an effective and robust method of sacrocaudal sensory afferent stimulation that induces motor activity, including alternating stepping. In this study, responsiveness to a tail pinch following treatment with quipazine (or saline vehicle control) was examined in spinal cord transected (at midthoracic level) and intact neonatal rats. Rat pups were secured in the supine posture with limbs unrestricted. Quipazine or saline was administered intraperitoneally and after a 10-min period, a tail pinch was administered. A 1-min baseline period prior to tail-pinch administration and a 1-min response period postpinch was observed and hind-limb motor activity, including locomotor-like stepping behavior, was recorded and analyzed. Neonatal rats showed an immediate and robust response to sensory stimulation induced by the tail pinch. Quipazine recovered hind-limb movement and step frequency in spinal rats back to intact levels, suggesting a synergistic, additive effect of 5-HT-receptor and sensory stimulation in spinal rats. Although levels of activity in spinal rats were restored with quipazine, movement quality (high vs. low amplitude) was only partially restored. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2011-03-01

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

  19. 5-HT2C receptor involvement in the control of persistence in the reinforced spatial alternation animal model of obsessive-compulsive disorder.

    Science.gov (United States)

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

    2013-04-15

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

  20. 4-[125I]iodo-(2,5-dimethoxy)phenylisopropylamine and [3H]ketanserin labeling of 5-hydroxytryptamine2 (5HT2) receptors in mammalian cells transfected with a rat 5HT2 cDNA: Evidence for multiple states and not multiple 5HT2 receptor subtypes

    International Nuclear Information System (INIS)

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

    1990-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  2. The 5-HT2C receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

    NARCIS (Netherlands)

    Janssen, Paddy Kc; Schaik, Ron van; Olivier, Berend|info:eu-repo/dai/nl/073067199; Waldinger, Marcel D|info:eu-repo/dai/nl/163958564

    2014-01-01

    It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2C receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2C receptor gene

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  4. Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells.

    Science.gov (United States)

    Galindo, Liliana; Moreno, Estefanía; López-Armenta, Fernando; Guinart, Daniel; Cuenca-Royo, Aida; Izquierdo-Serra, Mercè; Xicota, Laura; Fernandez, Cristina; Menoyo, Esther; Fernández-Fernández, José M; Benítez-King, Gloria; Canela, Enric I; Casadó, Vicent; Pérez, Víctor; de la Torre, Rafael; Robledo, Patricia

    2018-01-02

    Cannabinoid CB1 receptors (CB 1 R) and serotonergic 2A receptors (5HT 2A R) form heteromers in the brain of mice where they mediate the cognitive deficits produced by delta-9-tetrahydrocannabinol. However, it is still unknown whether the expression of this heterodimer is modulated by chronic cannabis use in humans. In this study, we investigated the expression levels and functionality of CB 1 R-5HT 2A R heteromers in human olfactory neuroepithelium (ON) cells of cannabis users and control subjects, and determined their molecular characteristics through adenylate cyclase and the ERK 1/2 pathway signaling studies. We also assessed whether heteromer expression levels correlated with cannabis consumption and cognitive performance in neuropsychological tests. ON cells from controls and cannabis users expressed neuronal markers such as βIII-tubulin and nestin, displayed similar expression levels of genes related to cellular self-renewal, stem cell differentiation, and generation of neural crest cells, and showed comparable Na + currents in patch clamp recordings. Interestingly, CB 1 R-5HT 2A R heteromer expression was significantly increased in cannabis users and positively correlated with the amount of cannabis consumed, and negatively with age of onset of cannabis use. In addition, a negative correlation was found between heteromer expression levels and attention and working memory performance in cannabis users and control subjects. Our findings suggest that cannabis consumption regulates the formation of CB 1 R-5HT 2A R heteromers, and may have a key role in cognitive processing. These heterodimers could be potential new targets to develop treatment alternatives for cognitive impairments.

  5. (11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand

    DEFF Research Database (Denmark)

    Andersen, Valdemar L; Hansen, Hanne D; Herth, Matthias M

    2015-01-01

    ]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs...

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

    Science.gov (United States)

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

    2016-01-01

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

  7. Studies To Examine Potential Tolerability Differences between the 5-HT2C Receptor Selective Agonists Lorcaserin and CP-809101.

    Science.gov (United States)

    Higgins, Guy A; Silenieks, Leonardo B; Patrick, Amy; De Lannoy, Ines A M; Fletcher, Paul J; Parker, Linda A; MacLusky, Neil J; Sullivan, Laura C; Chavera, Teresa A; Berg, Kelly A

    2017-05-17

    Lorcaserin (LOR) is a selective 5-HT 2C receptor agonist that has been FDA approved as a treatment for obesity. The most frequently reported side-effects of LOR include nausea and headache, which can be dose limiting. We have previously reported that in the rat, while LOR produced unconditioned signs characteristic of nausea/malaise, the highly selective 5-HT 2C agonist CP-809101 (CP) produced fewer equivalent signs. Because this may indicate a subclass of 5-HT 2C agonists having better tolerability, the present studies were designed to further investigate this apparent difference. In a conditioned gaping model, a rodent test of nausea, LOR produced significantly higher gapes compared to CP consistent with it having higher emetogenic properties. Subsequent studies were designed to identify features of each drug that may account for such differences. In rats trained to discriminate CP-809101 from saline, both CP and LOR produced full generalization suggesting a similar interoceptive cue. In vitro tests of functional selectivity designed to examine signaling pathways activated by both drugs in CHO (Chinese hamster ovary) cells expressing h5-HT 2C receptors failed to identify evidence for biased signaling differences between LOR and CP. Thus, both drugs showed similar profiles across PLC, PLA 2 , and ERK signaling pathways. In studies designed to examine pharmacokinetic differences between LOR and CP, while drug plasma levels correlated with increasing dose, CSF levels did not. CSF levels of LOR increased proportionally with dose; however CSF levels of CP plateaued from 6 to 12 mg/kg. Thus, the apparently improved tolerability of CP likely reflects a limit to CNS levels attained at relatively high doses.

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

    Science.gov (United States)

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

    2006-01-01

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

  9. Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice.

    Science.gov (United States)

    Moreno, José L; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C; González-Maeso, Javier

    2013-03-01

    Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT(2A) agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT(2A) receptor-dependent hallucinogenic effects of LSD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice

    Science.gov (United States)

    Moreno, José L.; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C.; González-Maeso, Javier

    2013-01-01

    Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT2A receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24 mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5 mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [3H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT2A agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT2A receptor-dependent hallucinogenic effects of LSD. PMID:23333599

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

    Science.gov (United States)

    Walker, Ellen A; Foley, John J

    2010-03-01

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

  12. 5-HT2a receptor in mPFC influences context-guided reconsolidation of object memory in perirhinal cortex

    Science.gov (United States)

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

    2018-01-01

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

  13. Obesitas dan hubungannya dengan polimorfisme gena promoter 5-HT2A, tekanan darah, profil lipid, kadar glukosa, dan malondialdehid

    Directory of Open Access Journals (Sweden)

    Pramudji Hastuti

    2011-10-01

    Full Text Available Background: Obesity among adults has risen significantly in the world-cutting across all ages, racial and ethnic groups and gender. The 5-HT 2A receptor is crucially involved in regulation of body weight and the appetite. Disturbances in the distribution and or gene regulation of the postsynaptic 5-HT2A receptor are implicated in the pathophysiology of conditions such as obesity, coronary heart disease, high blood pressure, diabetes, stroke dan some cancers. Objective: To test the association between obesity with polymorphism of promoter -1438G→A 5-HT2A receptors gene, blood pressure, lipid profiles, levels of blood glucose and malondialdehyde (MDA. Method: This cross-sectional study included thirty six unrelated obese young people (BMI ≥ 30 recruited from populations in Yogyakarta and 36 controls with age matched with BMI ≤ 25. Statistical differences between blood pressure, lipid profiles, glucose and MDA levels were assessed by t-test and genotypes by Chi square test. Results: There were no significant difference in blood pressure lipid profile, level of glucose and MDA in obese group compared with control (p>0,05. Allele A and G frequency in obese group 25% and 75% respectively, and controls 22.2% and 77.8% respectively, and no significant difference in all two groups, but G allele had higher risk to obese than A allele. Conclusion: These data indicated G allele was mild risk factor for obesity.

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

    Science.gov (United States)

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

    2017-06-01

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

  15. Association of 5-HT2A receptor gene polymorphisms with gastrointestinal disorders in Egyptian children with autistic disorder.

    Science.gov (United States)

    Abdelrahman, Hadeel M; Sherief, Laila M; Alghobashy, Ashgan A; Abdel Salam, Sanaa M; Hashim, Haitham M; Abdel Fattah, Nelly R; Mohamed, Randa H

    2014-11-12

    Gastrointestinal disturbances (GID) are frequently reported in children with autism spectrum disorders (ASD). Recently, mounting evidence suggests that there may be a genetic link for autism with gastrointestinal disturbances. We aimed to investigate whether there were any association between the -1438A/G, 102T/C and His452Tyr polymorphisms of the serotonin 2A receptor gene (5-HT2A) in Egyptian children with ASD and GID. Eighty children with autistic disorder and 100 healthy control children were examined. -1438A/G, 102T/C and His452Tyr polymorphisms of 5-HT2A were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Significant increase of the G allele and the GG genotype of the -1438A/G polymorphism was observed in children with autism than control, but there were no significant differences in the frequencies either of the 102T/C genotype or His452Tyr genotype between the two groups. There was a significant increase of homozygote A allele of the -1438A/G and CC genotype of the 102T/C polymorphism in ASD children with GID. This study supports the possible involvement of the 5-HT2A receptor in the development of ASD and associated GID. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Distribution of 5HT2A receptors in the human brain: Comparison of data in vivo and post mortem

    International Nuclear Information System (INIS)

    Forutan, F.; Estalji, S.; Beu, M.; Nikolaus, S.; Vosberg, H.; Mueller-Gaertner, H.W.; Larisch, R.; Hamacher, K.; Coenen, H.H.

    2002-01-01

    Aim: The study presented here firstly compars the distribution of the binding potential of the serotonin-5HT 2A receptor as measured in vivo with data of receptor density taken from literature. Secondly, the sensitivity of the method to detect gradual differences in receptor densities is evaluated. Methods: Positron emission tomography (PET) studies were carried out in 6 healthy volunteers using the selective serotonin-5HT 2A ligand 18 F-altanserin. The binding potential was quantified in 12 regions using Logan's graphical method and the equilibrium method. These data were compared to the distribution of receptor density as taken from literature. Results: The binding data in vivo correlated to autoradiography data (post mortem) with r = 0.83 (Pearson regression coefficient; p 18 F-altanserin and PET in healthy volunteers and the true autoradiographically determined distribution of 5HT 2A receptors in human brains. The in vivo method seems to be sensitive enough to detect changes in receptor density of more than 18%. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Bruno Pierre Guiard

    2015-03-01

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

  18. Varennes Tokamak

    International Nuclear Information System (INIS)

    Cumyn, P.B.

    A consortium of five organizations under the leadership of IREQ, the Institute de Recherche d'Hydro-Quebec has completed a conceptual design study for a tokamak device, and in January 1981 its construction was authorized with funding being provided principally by Hydro-Quebec and the National Research Council, as well as by the Ministre d'Education du Quebec and Natural Sciences and Engineering Research Council of Canada (NSERC). The device will form the focus of Canada's magnetic-fusion program and will be located in IREQ's laboratories in Varennes. Presently the machine layout is being finalized from the physics point of view and work has started on equipment design and specification. The Tokamak de Varennes will be an experimental device, the purpose of which is to study plasma and other fusion related phenomena. In particular it will study: 1. Plasma impurities and plasma/liner interaction; 2. Long pulse or quasi-continuous operation using plasma rampdown and eventually plasma current reversal in order to maintain the plasma; and 3. Advanced diagnostics

  19. Tokamak physics

    International Nuclear Information System (INIS)

    Haines, M.G.

    1984-01-01

    The physical conditions required for breakeven in thermonuclear fusion are derived, and the early conceptual ideas of magnetic confinement and subsequent development are followed, leading to present-day large scale tokamak experiments. Confinement and diffusion are developed in terms of particle orbits, whilst magnetohydrodynamic stability is discussed from energy considerations. From these ideas are derived the scaling laws that determine the physical size and parameters of this fusion configuration. It becomes clear that additional heating is required. However there are currently several major gaps in our understanding of experiments; the causes of anomalous electron energy loss and the major current disruption, the absence of the 'bootstrap' current and what physics determines the maximum plasma pressure consistent with stability. The understanding of these phenomena is a major challenge to plasma physicists. (author)

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  2. In vivo binding of 125I-LSD to serotonin 5-HT2 receptors in mouse brain

    International Nuclear Information System (INIS)

    Hartig, P.R.; Scheffel, U.; Frost, J.J.; Wagner, H.N. Jr.

    1985-01-01

    The binding of 125 I-LSD (2-[ 125 I]-lysergic acid diethylamide) was studied in various mouse brain regions following intravenous injection of the radioligand. The high specific activity of 125 I-LSD enabled the injection of low mass doses (14ng/kg), which are well below the threshold for induction of any known physiological effect of the probe. The highest levels of 125 I-LSD binding were found in the frontal cortex, olfactory tubercles, extra-frontal cortex and striatum while the lowest level was found in the cerebellum. Binding was saturable in the frontal cortex but increased linearly in the cerebellum with increasing doses of 125 I-LSD. Serotonergic compounds potently inhibited 125 I-LSD binding in cortical regions, olfactory tubercles, and hypothalamus but had no effect in the cerebellum. Dopaminergic compounds caused partial inhibition of binding in the striatum while adrenergic compounds were inactive. From these studies the authors conclude that 125 I-LSD labels serotonin 5-HT 2 receptor sites in cortical regions with no indication that other receptor sites are labeled. In the olfactory tubercles and hypothalamus, 125 I-LSD labeling occurs predominantly or entirely at serotonic 5-HT 2 sites. In the striatum, 125 I-LSD labels approximately equal proportions of serotonergic and dopaminergic sites. These data indicate that 125 I-LSD labels serotonin receptors in vivo and suggests that appropriate derivatives of 2I-LSD may prove useful for tomographic imaging of serotonin 5-HT 2 receptors in the mammalian cortex

  3. Multicompartmental study of fluorine-18 altanserin binding to brain 5HT2 receptors in humans using positron emission tomography

    International Nuclear Information System (INIS)

    Biver, F.; Goldman, S.; Luxen, A.; Monclus, M.; Forestini, M.; Mendlewicz, J.; Lotstra, F.

    1994-01-01

    Serotoninergic type 2 (5HT 2 ) receptors have been implicated in the regulation of many brain functions in humans and may play a role in several neurological and psychiatric diseases. Fluorine-18 altanserin has been proposed as a new radiotracer for the study of 5HT 2 receptors by PET because of its high affinity for 5HT 2 receptors (Ki: 0.13 nM) and its good specificity in in vitro studies. Dynamic PET studies were carried out in 12 healthy volunteers after intravenous injection of 0.1 mCi/kg [ 18 F] altanserin. Ninety minutes after injection, we observed mainly cortical binding. Basal ganglia and cerebellum showed very low uptake and the frontal cortex to cerebellum ratio was about 3. To evaluate the quantitative distribution of this ligand in the brain, we used two different methods of data analysis: a four-compartment model was used to achieve quantitative evaluation of rate constants (K 1 and k 2 through k 6 ) by non-linear regression, and a multiple-time graphical analysis technique for reversible binding was employed for the measurement of k 1 /k 2 and k 3 /k 4 ratios. Using both methods, we found significant differences in binding capacity (estimated by k 3 /k 4 = B max /K d ) between regions, the values increasing as follows: occipital, limbic, parietal, frontal and temporal cortex. After correction of values obtained by the graphical method for the existence of non-specific binding, results generated by the two methods were consistent. (orig.)

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  7. Cerebral 5-HT2A receptor and serotonin transporter binding in humans are not affected by the val66met BDNF polymorphism status or blood BDNF levels

    DEFF Research Database (Denmark)

    Klein, Anders Bue; Trajkovska, Viktorija; Erritzoe, David

    2010-01-01

    Recent studies have proposed an interrelation between the brain-derived neurotrophic factor (BDNF) val66met polymorphism and the serotonin system. In this study, we investigated whether the BDNF val66met polymorphism or blood BDNF levels are associated with cerebral 5-hydroxytryptamine 2A (5-HT(2A......)) receptor or serotonin transporter (SERT) binding in healthy subjects. No statistically significant differences in 5-HT(2A) receptor or SERT binding were found between the val/val and met carriers, nor were blood BDNF values associated with SERT binding or 5-HT(2A) receptor binding. In conclusion, val66met...... BDNF polymorphism status is not associated with changes in the serotonergic system. Moreover, BDNF levels in blood do not correlate with either 5-HT(2A) or SERT binding....

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

    Directory of Open Access Journals (Sweden)

    Simon R O Nilsson

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

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

    Science.gov (United States)

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

    2009-02-01

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

  10. Longitudinal assessment of cerebral 5-HT2A receptors in healthy elderly volunteers: an [18F]-altanserin PET study

    DEFF Research Database (Denmark)

    Marner, Lisbeth; Knudsen, Gitte M; Haugbøl, Steven

    2009-01-01

    patients with neuropsychiatric diseases on a longitudinal basis. METHODS: [(18)F]-Altanserin PET was used to quantify 5-HT(2A) receptors in 12 healthy elderly individuals at baseline and at 2 years in six volumes of interest. A bolus/infusion protocol was used to achieve the binding potential, BP(P...... of our measurements over 2 years with the stability of data from an earlier study with 2-week test-retest measurements. RESULTS: BP(P) was unaltered at follow-up without the use of PV correction and when applying two-tissue PV correction, test-retest reproducibility was 12-15% and reliability 0...

  11. PPPL tokamak program

    International Nuclear Information System (INIS)

    Furth, H.P.

    1984-10-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2015-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Xavier Viñals

    2015-07-01

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

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

    OpenAIRE

    Preuss, Ulrich W.; Koller, G.; Bondy, Brigitta; Bahlmann, Miriam; Soyka, Michael

    2001-01-01

    Objective: Impulsive behavior in alcoholics puts them at serious risk of severer course of disease and has been related to the serotonergic neurotransmission dysfunction. The aim of this study is to investigate the association between impulsive aggression in alcohol dependents with regard to the G-1438A polymorphism in the promoter region of the 5-HT2A receptor gene. Furthermore, we investigated the statistical interaction between 5-HT2A alleles, antisocial personality disorder (APD) and impu...

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

    Directory of Open Access Journals (Sweden)

    Marília Greidinger Carvalho

    2012-04-01

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

  17. Status of tokamak research

    International Nuclear Information System (INIS)

    Rawls, J.M.

    1979-10-01

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

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

    Science.gov (United States)

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

    2013-01-23

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

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  20. Tokamak Systems Code

    International Nuclear Information System (INIS)

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

    1985-03-01

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

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

    Science.gov (United States)

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

    2015-03-15

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

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

    Science.gov (United States)

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

    2002-11-01

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

  3. Tokamak devices: towards controlled fusion

    International Nuclear Information System (INIS)

    Trocheris, M.

    1975-01-01

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

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

    Science.gov (United States)

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

    2017-11-15

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

  5. Polimorfismos dos genes do receptor de serotonina (5-HT2A e da catecol-O-metiltransferase (COMT: fatores desencadeantes da fibromialgia? Serotonin receptor (5-HT 2A and catechol-O-methyltransferase (COMT gene polymorphisms: Triggers of fibromyalgia?

    Directory of Open Access Journals (Sweden)

    Josie Budag Matsuda

    2010-04-01

    Full Text Available INTRODUÇÃO: A fibromialgia é uma síndrome reumática caracterizada por dor difusa e crônica associada a fadiga, insônia, ansiedade, depressão, perda de memória e tontura. Embora os mecanismos fisiológicos que controlam a fibromialgia não tenham sido estabelecidos, fatores neuroendócrinos, genéticos ou moleculares podem estar envolvidos. OBJETIVO: O objetivo do presente estudo foi caracterizar os polimorfismos dos genes do receptor de serotonina (5-HT2A e da catecolO-metiltransferase (COMT em pacientes brasileiros com fibromialgia, a fim de avaliar sua participação na etiologia da doença. MATERIAL E MÉTODOS: O DNA genômico extraído de 102 amostras de sangue (51 pacientes, 51 controles foi usado para a caracterização molecular dos polimorfismos dos genes 5-HT2A e COMT, por meio de PCR-RFLP. RESULTADOS: A análise molecular dos polimorfismos do gene 5-HT2A demonstrou frequências de 25,49% C/C, 49,02% T/C e 25,49% T/T, nos pacientes com fibromialgia, e 17,65% C/C, 62,74% T/C e 19,61% T/T, no grupo controle, não apresentando diferença significativa entre o grupo de pacientes e o grupo controle. Os polimorfismos do gene da COMT em pacientes com fibromialgia apresentaram uma frequência de 17,65% e 45,10% para os genótipos H/H e L/H, respectivamente. No grupo controle, as frequências foram de 29,42%, para H/H, e 60,78%, para L/H, sem diferença significativa entre ambos os grupos. Entretanto, houve diferença significativa na frequência do genótipo L/L em pacientes (37,25% e controles (9,8%, o que permitiu a diferenciação entre os dois grupos. CONCLUSÃO: A frequência do genótipo L/L foi maior nos pacientes com fibromialgia. Apesar de a fibromialgia envolver uma situação poligênica e fatores ambientais, o estudo molecular do SNP rs4680 do gene da COMT pode auxiliar a identificação de indivíduos suscetíveis.INTRODUCTION: Fibromyalgia is a rheumatic syndrome characterized by diffuse and chronic pain associated with

  6. Specific in vivo binding in the rat brain of [18F]RP 62203: A selective 5-HT2A receptor radioligand for positron emission tomography

    International Nuclear Information System (INIS)

    Besret, Laurent; Dauphin, Francois; Huard, Cecile; Lasne, Marie-Claire; Vivet, Richard; Mickala, Patrick; Barbelivien, Alexandra; Baron, Jean-Claude

    1996-01-01

    In vivo pharmacokinetic and brain binding characteristics of [ 18 F]RP 62203, a selective high-affinity serotonergic 5-HT 2A receptor antagonist, were assessed in the rat following intravenous injection of trace amount of the radioligand. The radioactive distribution profile observed in the brain 60 min after injection was characterized by greater than fourfold higher uptake in neocortex as compared to cerebellum (0.38 ± 0.07% injected dose/g, % ID/g and 0.08 ± 0.01 ID/g, respectively), consistent with in vivo specific binding to the 5-HT 2A receptor. Furthermore, specific [ 18 F]RP 62203 binding significantly correlated with the reported in vitro distribution of 5-HT 2A receptors, but not with known concentration profiles of dopaminergic D 2 or adrenergic α 1 receptors. Finally, detectable specific binding was abolished by pretreatment with large doses of ritanserin, a selective 5-HT 2A antagonist, which resulted in uniform uptakes across cortical, striatal and cerebellar tissues. Thus, [ 18 F]RP 62203 appears to be a promising selective tool to visualize and quantify 5-HT 2A brain receptors in vivo with positron emission tomography

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  8. Liraglutide, a GLP-1 Receptor Agonist, Which Decreases Hypothalamic 5-HT2A Receptor Expression, Reduces Appetite and Body Weight Independently of Serotonin Synthesis in Mice

    Directory of Open Access Journals (Sweden)

    Katsunori Nonogaki

    2018-01-01

    Full Text Available A recent report suggested that brain-derived serotonin (5-HT is critical for maintaining weight loss induced by glucagon-like peptide-1 (GLP-1 receptor activation in rats and that 5-HT2A receptors mediate the feeding suppression and weight loss induced by GLP-1 receptor activation. Here, we show that changes in daily food intake and body weight induced by intraperitoneal administration of liraglutide, a GLP-1 receptor agonist, over 4 days did not differ between mice treated with the tryptophan hydroxylase (Tph inhibitor p-chlorophenylalanine (PCPA for 3 days and mice without PCPA treatment. Treatment with PCPA did not affect hypothalamic 5-HT2A receptor expression. Despite the anorexic effect of liraglutide disappearing after the first day of treatment, the body weight loss induced by liraglutide persisted for 4 days in mice treated with or without PCPA. Intraperitoneal administration of liraglutide significantly decreased the gene expression of hypothalamic 5-HT2A receptors 1 h after injection. Moreover, the acute anorexic effects of liraglutide were blunted in mice treated with the high-affinity 5-HT2A agonist (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl methylamine hydrobromide 14 h or 24 h before liraglutide injection. These findings suggest that liraglutide reduces appetite and body weight independently of 5-HT synthesis in mice, whereas GLP-1 receptor activation downregulates the gene expression of hypothalamic 5-HT2A receptors.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  10. [Other Possible Clinical Applications of Drugs with 5HT2A effect in Liaison Psychiatry: Cases Report].

    Science.gov (United States)

    Corredor, Catalina Ayala; Castillo, Carolina Solís

    2012-03-01

    In liaison psychiatry it is possible to get an integral view of patient's treatment and needs, paying special attention to pharmacological interactions and contraindications. Some particular cases motivated the description, report and review about other possible applications of 5HT2A and 5HT3 antagonist, particularly Mirtazapine and Olanzapine, in hyperalgesia syndrome, tinnitus and Progressive Multifocal Leukoencephalopathy by JC virus. Cases report. We describe 3 cases of patients in which Mirtazapine and Olanzapine were necessary not only to control psychiatric symptoms (affective / behavioral symptoms and insomnia) but to act as adjuvant therapy in axis III diseases. The use of any drug in psychiatry must take in to account the context of the patient, the presence of comorbidity, contraindications and pharmacological interactions so as to grant a positive outcome also promoting the multidisciplinary work between specialists. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  11. Radiosynthesis of a new radiobrominated ligand for 5HT2A receptors, a potential tracer for PET

    International Nuclear Information System (INIS)

    Terriere, D.; Hermanne, A.; Sonck, M.; Mertens, J.; Leysen, J.E.

    1997-01-01

    4-Amino-N-[1-[3-(4-fluorophenoxy)propyl]propyl]-4-methyl-4-pipe ridinyl]-2-methoxybenzamide, a compound with high affinity for 5HT 2 -receptors, was radiobrominated in the 5-position of the methoxybenzamide group by electrophilic substitution. Hydrogen peroxide/acetic acid, peracetic acid and a mixture of both were tried as oxidants. Radiobromination with the hydrogen peroxide method gave a labelling yield of 80% in the 5-position and 20% in the 3-position without any side products. On the other hand the labelling methods based on the use of peracetic acid gave a more selective radiobromination in the 5-position, but with low yields and moreover generated radioactive and non-radioactive side products. N.C.A radiobromide of high radio-chemical purity was obtained by an ion-exchange procedure on the target material solution coupled to a purification step using methanol. (Author)

  12. Tokamak engineering mechanics

    International Nuclear Information System (INIS)

    Song, Yuntao; Wu, Weiyue; Du, Shijun

    2014-01-01

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

  13. Tokamak engineering mechanics

    CERN Document Server

    Song, Yuntao; Du, Shijun

    2013-01-01

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

  14. Advanced Tokamak Stability Theory

    Science.gov (United States)

    Zheng, Linjin

    2015-03-01

    The intention of this book is to introduce advanced tokamak stability theory. We start with the derivation of the Grad-Shafranov equation and the construction of various toroidal flux coordinates. An analytical tokamak equilibrium theory is presented to demonstrate the Shafranov shift and how the toroidal hoop force can be balanced by the application of a vertical magnetic field in tokamaks. In addition to advanced theories, this book also discusses the intuitive physics pictures for various experimentally observed phenomena.

  15. Tokamak confinement scaling laws

    International Nuclear Information System (INIS)

    Connor, J.

    1998-01-01

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

  16. Tokamak concept innovations

    International Nuclear Information System (INIS)

    1986-04-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

  18. Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L

    2016-08-01

    Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys. Behavior was maintained under a concurrent schedule of food delivery (1g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0-10mg/kg/day, intramuscular) treatment periods. Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2-10mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets. Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights

  19. The 5-HT2C receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

    Directory of Open Access Journals (Sweden)

    Paddy KC Janssen

    2014-08-01

    Full Text Available It has been postulated that the persistent short intravaginal ejaculation latency time (IELT of men with lifelong premature ejaculation (LPE is related to 5-hydroxytryptamine (HT2C receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2C receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2C receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2C receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9 s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60 s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2C receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys is significantly lower (22.6 s; 95% CI 18.3-27.8 s than in male homozygous mutants (Ser/Ser (40.4 s; 95% CI 20.3-80.4 s (P = 0.03. It is concluded that Cys23Ser 5-HT2C receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

  20. The 5-HT2C receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation.

    Science.gov (United States)

    Janssen, Paddy Kc; Schaik, Ron van; Olivier, Berend; Waldinger, Marcel D

    2014-01-01

    It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2C receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2C receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2C receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2C receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9 s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60 s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2C receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6 s; 95% CI 18.3-27.8 s) than in male homozygous mutants (Ser/Ser) (40.4 s; 95% CI 20.3-80.4 s) (P = 0.03). It is concluded that Cys23Ser 5-HT2C receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

  1. Abeta(1-42) injection causes memory impairment, lowered cortical and serum BDNF levels, and decreased hippocampal 5-HT(2A) levels

    DEFF Research Database (Denmark)

    Christensen, R; Marcussen, Anders Bue; Wörtwein, Gitta

    2008-01-01

    was used to monitor Abeta(1-42) induced memory impairment. Memory impairment was seen 22 days after injection of Abeta(1-42) in the experimental group and until termination of the experiments. In the Abeta(1-42) injected animals we saw an abolished increase in serum BDNF levels that was accompanied...... by significant lower BDNF levels in frontal cortex and by an 8.5% reduction in hippocampal 5-HT(2A) receptor levels. A tendency towards lowered cortical 5-HT(2A) was also observed. These results indicate that the Abeta(1-42) associated memory deficit is associated with an impaired BDNF regulation, which...

  2. Tokamak control simulator

    International Nuclear Information System (INIS)

    Edelbaum, T.N.; Serben, S.; Var, R.E.

    1976-01-01

    A computer model of a tokamak experimental power reactor and its control system is being constructed. This simulator will allow the exploration of various open loop and closed loop strategies for reactor control. This paper provides a brief description of the simulator and some of the potential control problems associated with this class of tokamaks

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

    Science.gov (United States)

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

    2014-02-01

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

  4. Evidence for a role of 5-HT2C receptors in the motor aspects of performance, but not the efficacy of food reinforcers, in a progressive ratio schedule

    NARCIS (Netherlands)

    Bezzina, G.; Body, S.; Cheung, T.H.; Hampson, C.L.; Bradshaw, C.M.; Glennon, J.C.; Szabadi, E.

    2015-01-01

    RATIONALE: 5-Hydroxytryptamine2C (5-HT2C) receptor agonists reduce the breakpoint in progressive ratio schedules of reinforcement, an effect that has been attributed to a decrease of the efficacy of positive reinforcers. However, a reduction of the breakpoint may also reflect motor impairment.

  5. Scientific opinion on the appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms

    DEFF Research Database (Denmark)

    Petersen, Annette

    The EFSA Panel on Contaminants in the Food Chain (CONTAM) established a tolerable daily intake (TDI) for T2 and HT2 of 0.02 μg/kg body weight (bw) per day based on a new in vivo subchronic toxicity study in rats that confirmed that immune- and haematotoxicity are the critical effects of T2...

  6. Long-term estrogen therapy and 5-HT(2A) receptor binding in postmenopausal women; a single photon emission tomography (SPET) study

    NARCIS (Netherlands)

    Compton, J.; Travis, M. J.; Norbury, R.; Erlandsson, K.; van Amelsvoort, T.; Daly, E.; Waddington, W.; Matthiasson, P.; Eersels, J. L. H.; Whitehead, M.; Kerwin, R. W.; Ell, P. J.; Murphy, D. G. M.

    2008-01-01

    Variation in estrogen level is reported by some to affect brain maturation and memory. The neurobiological basis for this may include modulation of the serotonergic system. No neuroimaging studies have directly examined the effect of extended estrogen therapy (ET), on the 5-HT(2A) receptor in human

  7. A database of [(18)F]-altanserin binding to 5-HT(2A) receptors in normal volunteers: normative data and relationship to physiological and demographic variables

    DEFF Research Database (Denmark)

    Adams, Karen H; Pinborg, Lars H; Svarer, Claus

    2004-01-01

    This study presents the results of an analysis of 5-hydroxytryptamine (5-HT)(2A) receptors in 52 healthy subjects. Thirty men and twenty-two women aged between 21 and 79 years were investigated with magnetic resonance imaging (MRI) and [(18)F]-altanserin positron emission tomography (PET). The di...

  8. S32006, a novel 5-HT(2C) receptor antagonist displaying broad-based antidepressant and anxiolytic properties in rodent models

    NARCIS (Netherlands)

    Dekeyne, Anne; la Cour, Clotilde Mannoury; Gobert, Alain; Brocco, Mauricette; Lejeune, Francoise; Serres, Florence; Sharp, Trevor; Daszuta, Annie; Soumier, Amelie; Papp, Mariusz; Rivet, Jean-Michel; Flik, Gunnar; Cremers, Thomas I.; Muller, Olivier; Lavielle, Gilbert; Millan, Mark J.

    Rationale Serotonin (5-HT)(2C) receptors are implicated in the control of mood, and their blockade is of potential interest for the management of anxiodepressive states. Objectives Herein, we characterized the in vitro and in vivo pharmacological profile of the novel benzourea derivative, S32006.

  9. Decreased hippocampal 5-HT2A receptors in post mortem tissue from schizophrenic but not bipolar subjects

    International Nuclear Information System (INIS)

    Scarr, E.; Pavey, G.; Bradbury, R.; Copolov, D.L.; Dean, B.

    2001-01-01

    Full text: The hippocampus is important in cognition and sensory gating,both of which are thought to be impaired in schizophrenia. Since 5HT has also been implicated in cognition we investigated the hippocampal serotonergic system in subjects with either schizophrenia or bipolar mood disorder. Using autoradiography,we found significant (p 3 H] ketanserin binding in the CA3 (Mean ±SEM:29.6 ± 4.0 vs.46.6 ± 4.2 fmol/mgETE), the stratum radiatum (27.3 ± 2.7 vs.38.7 ± 3.9 fmol/mgETE) and pyramidal cell layer (35.6 ± 3.4 vs.51.4 ± 2.7 fmol/ mgETE) of CA1 as well as the outer (8.3 ± 1.5 vs.12.2 ± 1.4 fmol/mgETE) and pyramidal cell layer (16.4 ± 2.5 vs.32.1 ± 3.2 fmol/mgETE) of the subiculum in hippocampal tissue from schizophrenic subjects. No such differences were found in the dentate gyrus or CA2 region from schizophrenia subjects or in any hippocampal region from bipolar subjects. The lack of change in the bipolar cohort suggests that the decreased density of hippocampal 5-HT 2A receptors is disease specific and not a result of neuroleptic treatment, which both cohorts received. Copyright (2001) Australian Neuroscience Society

  10. Synergistic effect of 5-HT2A receptor gene and MAOA gene on the negative emotion of patients with depression.

    Science.gov (United States)

    Guo, Huirong; Ren, Yuming; Zhao, Ning; Wang, Yali; Li, Shuying; Cui, He; Zhang, Sijia; Zhang, Jianhua

    2014-07-01

    To analyse the synergistic effect of polymorphism of the tandem repeat sequence u-VNTR of 5-hydroxytryptamine 2A (5-HT2A) receptor gene and monoamine oxidase A (MAOA) gene on the negative emotion in frontal lobe of patients with depression through functional magnetic resonance imaging (fMRI) technique. Functional magnetic resonance imaging scanning was performed for 72 patients with depression and 70 gender, age-matched healthy people with physical examination under negative emotion recognition task. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was adopted to analyse genotype. The superior, middle and inferior gyrus of bilateral frontal lobe was regarded as the brain region of interest, and then the difference of activation intensity in frontal lobe subregion between control groups and patient groups with different genotypes, and the interaction between the two kinds of polymorphism were compared. The activation intensity in right frontal middle gyrus of patients with CC genotype increased obviously compared with TT and TC genotype patient groups and TT genotype control group (Peffect of the two genotypes on the activation abnormality of negative emotion recognition in right frontal middle gyrus (F = 6·18, P = 0·029). The negative activation in right frontal middle gyrus of patients with CC+H genotypes increased most obviously (Peffect on the activity abnormality when recognizing negative emotion in right frontal middle gyrus of patients with depression. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2001-01-01

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

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

    Science.gov (United States)

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

    2009-05-01

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

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Claudia Röser

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

  17. Initial evaluation of 123I-5-I-R91150, a selective 5-HT2Aligand for single-photon emission tomography, in healthy human subjects

    International Nuclear Information System (INIS)

    Busatto, G.F.; Pilowsky, L.S.; Costa, D.C.; Mertens, J.; Terriere, D.; Ell, P.J.; Mulligan, R.; Travis, M.J.; Leysen, J.E.; Lui, D.; Gacinovic, S.; Waddington, W.; Lingford-Hughes, A.; Kerwin, R.W.

    1997-01-01

    The mapping of 5-HT 2 receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methox ybenzamide ( 123 I-5-I-R91150 or 123 I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT 2A receptors. This study reports on preliminary 123 I-5-I-R91150 SPET, whole-body and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SME-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT 2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100-120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT 2A receptors in humans (cerebral cortex >striatum >cerebellum). These findings suggest that 123 I-5-I-R91150 may be used for the imaging of 5-HT 2A receptors in the living human brain with SPET. (orig.). With 4 figs., 2 tabs

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

    Science.gov (United States)

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

    2009-12-01

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

  19. Tokamaks. 2. ed.

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  20. Tokamak reactor studies

    International Nuclear Information System (INIS)

    Baker, C.C.

    1981-01-01

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

  1. Tokamak ARC damage

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  2. Survey of Tokamak experiments

    International Nuclear Information System (INIS)

    Bickerton, R.J.

    1977-01-01

    The survey covers the following topics:- Introduction and history of tokamak research; review of tokamak apparatus, existing and planned; remarks on measurement techniques and their limitations; main results in terms of electron and ion temperatures, plasma density, containment times, etc. Empirical scaling; range of operating densities; impurities, origin, behaviour and control (including divertors); data on fluctuations and instabilities in tokamak plasmas; data on disruptive instabilities; experiments on shaped cross-sections; present experimental evidence on β limits; auxiliary heating; experimental and theoretical problems for the future. (author)

  3. Tokamak ARC damage

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-01-01

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

  4. Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure.

    Science.gov (United States)

    Martin, Corby K; Redman, Leanne M; Zhang, Jinkun; Sanchez, Matilde; Anderson, Christen M; Smith, Steven R; Ravussin, Eric

    2011-03-01

    Lorcaserin, a selective 5-hydroxytryptamine (5-HT)(2C) receptor agonist, reduces body weight. It is unclear whether weight loss is due to reduced energy intake (EI) or also to enhanced energy expenditure (EE). This study tested the effect of lorcaserin on EI and EE. In a double-blind, randomized, placebo-controlled trial, 57 (39 women) overweight and obese (body mass index, 27-45 kg/m(2)) adults were randomized to placebo (n = 28) or 10 mg twice daily lorcaserin (n = 29) for 56 d. Weight maintenance was imposed during d 1-7. Beginning on d 8, participants followed a diet and exercise plan targeting a 600 kcal/d deficit. At baseline and after 7 and 56 d of treatment, we measured body weight, body composition (dual x-ray absorptiometry), blood pressure, heart rate, EI at lunch and dinner, subjective appetite ratings, and 24-h EE and 24-h-respiratory quotient (RQ), measured by indirect calorimetry in a respiratory chamber. After 7 d of weight maintenance, EI was significantly (P kcal; placebo, -147 ± 89 kcal). After 56 d, lorcaserin resulted in significantly larger reductions in body weight (lorcaserin, -3.8 ± 0.4 kg; placebo, -2.2 ± 0.5 kg; P kcal; placebo, -205 ± 91 kcal; P < .05), and appetite ratings than in placebo. Changes in 24-h EE and 24-h RQ did not differ between groups, even after 24-h EE was adjusted for body weight and composition. Compared with placebo, lorcaserin had no effect on systolic or diastolic blood pressure or heart rate after 56 d. Lorcaserin reduces body weight through reduced EI, not altered EE or RQ.

  5. Relationship of obstructive sleep apnea syndrome with the 5-HT2A receptor gene in Brazilian patients.

    Science.gov (United States)

    de Carvalho, Thiago Bittencourt Ottoni; Suman, Marcela; Molina, Fernando Drimel; Piatto, Vânia Belintani; Maniglia, José Victor

    2013-03-01

    Serotonin (5-HT) regulates a variety of visceral and physiological functions, including sleep. Polymorphisms in the 5-HT2A receptor gene can alter its transcription, affecting the number of receptors in the serotoninergic system, contributing to obstructive sleep apnea syndrome (OSAS). The aim of this study was to determine the prevalence of the 102T-C and -1438G-A polymorphisms in the 5-HTR2A gene in Brazilian patients with and without OSAS. A cross-sectional study performed at the Otorhinolaryngology and Sleep Disorder Out Clinics, São José do Rio Preto Medical School, FAMERP. One hundred patients were examined as index cases and 100 persons as controls, of both genders to both groups. DNA was extracted from peripheral blood leukocytes, and the sites that encompassed both polymorphisms were amplified by PCR-RFLP. There was a significant prevalence of the male gender in index cases compared with the control group gender (p < 0.0001). There was no significant genotypic difference in the 102T-C polymorphism between the case and control groups (p = 1.000). The AA genotype of the -1438G-A polymorphism was more prevalent in the patients with OSAS compared with the controls (OR, 2.3; CI 95% 1.20-4.38; p = 0.01). There was no difference in the prevalence of the 102T-C polymorphism between patients with OSAS and the control group. Serotoninergic system dysfunction appeared to be related to OSAS. The -1438G-A polymorphism and OSAS are related in this studied Brazilian population.

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

    Directory of Open Access Journals (Sweden)

    Mei-Yan Liu

    2015-01-01

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

  7. Mutagenesis Analysis Reveals Distinct Amino Acids of the Human Serotonin 5-HT2C Receptor Underlying the Pharmacology of Distinct Ligands.

    Science.gov (United States)

    Liu, Yue; Canal, Clinton E; Cordova-Sintjago, Tania C; Zhu, Wanying; Booth, Raymond G

    2017-01-18

    While exploring the structure-activity relationship of 4-phenyl-2-dimethylaminotetralins (PATs) at serotonin 5-HT 2C receptors, we discovered that relatively minor modification of PAT chemistry impacts function at 5-HT 2C receptors. In HEK293 cells expressing human 5-HT 2C-INI receptors, for example, (-)-trans-3'-Br-PAT and (-)-trans-3'-Cl-PAT are agonists regarding Gα q -inositol phosphate signaling, whereas (-)-trans-3'-CF 3 -PAT is an inverse agonist. To investigate the ligand-receptor interactions that govern this change in function, we performed site-directed mutagenesis of 14 amino acids of the 5-HT 2C receptor based on molecular modeling and reported G protein-coupled receptor crystal structures, followed by molecular pharmacology studies. We found that S3.36, T3.37, and F5.47 in the orthosteric binding pocket are critical for affinity (K i ) of all PATs tested, we also found that F6.44, M6.47, C7.45, and S7.46 are primarily involved in regulating EC/IC 50 functional potencies of PATs. We discovered that when residue S5.43, N6.55, or both are mutated to alanine, (-)-trans-3'-CF 3 -PAT switches from inverse agonist to agonist function, and when N6.55 is mutated to leucine, (-)-trans-3'-Br-PAT switches from agonist to inverse agonist function. Notably, most point-mutations that affected PAT pharmacology did not significantly alter affinity (K D ) of the antagonist radioligand [ 3 H]mesulergine, but every mutation tested negatively impacted serotonin binding. Also, amino acid mutations differentially affected the pharmacology of other commercially available 5-HT 2C ligands tested. Collectively, the data show that functional outcomes shared by different ligands are mediated by different amino acids and that some 5-HT 2C receptor residues important for pharmacology of one ligand are not necessarily important for another ligand.

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

    Directory of Open Access Journals (Sweden)

    Almeida R.M.M. de

    2005-01-01

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

  9. 5-HT2A receptors in the feline brain: 123I-5-I-R91150 kinetics and the influence of ketamine measured with micro-SPECT.

    Science.gov (United States)

    Waelbers, Tim; Polis, Ingeborgh; Vermeire, Simon; Dobbeleir, André; Eersels, Jos; De Spiegeleer, Bart; Audenaert, Kurt; Slegers, Guido; Peremans, Kathelijne

    2013-08-01

    Subanesthetic doses of ketamine can be used as a rapid-acting antidepressant in patients with treatment-resistant depression. Therefore, the brain kinetics of (123)I-5-I-R91150 (4-amino-N-[1-[3-(4-fluorophenyl)propyl]-4-methylpiperidin-4-yl]-5-iodo-2-methoxybenzamide) and the influence of ketamine on the postsynaptic serotonin-2A receptor (5-hydroxytryptamine-2A, or 5-HT2A) status were investigated in cats using micro-SPECT. This study was conducted on 6 cats using the radioligand (123)I-5-I-R91150, a 5-HT2A receptor antagonist, as the imaging probe. Anesthesia was induced and maintained with a continuous-rate infusion of propofol (8.4 ± 1.2 mg kg(-1) followed by 0.22 mg kg(-1) min(-1)) 75 min after tracer administration, and acquisition of the first image began 15 min after induction of anesthesia. After this first acquisition, propofol (0.22 mg kg(-1) min(-1)) was combined with ketamine (5 mg kg(-1) followed by 0.023 mg kg(-1) min(-1)), and the second acquisition began 15 min later. Semiquantification, with the cerebellum as a reference region, was performed to calculate the 5-HT2A receptor binding indices (parameter for available receptor density) in the frontal and temporal cortices. The binding indices were analyzed with Wilcoxon signed ranks statistics. The addition of ketamine to the propofol continuous-rate infusion resulted in decreased binding indices in the right frontal cortex (1.25 ± 0.22 vs. 1.45 ± 0.16; P = 0.028), left frontal cortex (1.34 ± 0.15 vs. 1.49 ± 0.10; P = 0.028), right temporal cortex (1.30 ± 0.17 vs. 1.45 ± 0.09; P = 0.046), and left temporal cortex (1.41 ± 0.20 vs. 1.52 ± 0.20; P = 0.046). This study showed that cats can be used as an animal model for studying alterations of the 5-HT2A receptor status with (123)I-5-I-R91150 micro-SPECT. Furthermore, an interaction between ketamine and the 5-HT2A receptors resulting in decreased binding of (123)I-5-I-R91150 in the frontal and temporal cortices was demonstrated. Whether the

  10. Tokamak simulation code manual

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  11. Reproducibility of 5-HT2A receptor measurements and sample size estimations with [18F]altanserin PET using a bolus/infusion approach

    DEFF Research Database (Denmark)

    Haugbøl, Steven; Pinborg, Lars H; Arfan, Haroon M

    2006-01-01

    PURPOSE: To determine the reproducibility of measurements of brain 5-HT2A receptors with an [18F]altanserin PET bolus/infusion approach. Further, to estimate the sample size needed to detect regional differences between two groups and, finally, to evaluate how partial volume correction affects...... reproducibility and the required sample size. METHODS: For assessment of the variability, six subjects were investigated with [18F]altanserin PET twice, at an interval of less than 2 weeks. The sample size required to detect a 20% difference was estimated from [18F]altanserin PET studies in 84 healthy subjects....... Regions of interest were automatically delineated on co-registered MR and PET images. RESULTS: In cortical brain regions with a high density of 5-HT2A receptors, the outcome parameter (binding potential, BP1) showed high reproducibility, with a median difference between the two group measurements of 6...

  12. Comparison of T-2 Toxin and HT-2 Toxin Distributed in the Skeletal System with That in Other Tissues of Rats by Acute Toxicity Test.

    Science.gov (United States)

    Yu, Fang Fang; Lin, Xia Lu; Yang, Lei; Liu, Huan; Wang, Xi; Fang, Hua; Lammi, ZMikko J; Guo, Xiong

    2017-11-01

    Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone, knee joints, and costal cartilage) were significantly higher than those in the heart, liver, and kidneys (P skeletal system (thighbone and costal cartilage) were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  13. A PET [18F]altanserin study of 5-HT2A receptor binding in the human brain and responses to painful heat stimulation

    DEFF Research Database (Denmark)

    Kupers, Ronny Clement Florent; Frokjaer, Vibe G; Naert, Arne

    2009-01-01

    There is a large body of evidence that serotonin [5-hydroxytryptamine (5-HT)] plays an important role in the transmission and regulation of pain. Here we used positron emission tomography (PET) to study the relationship between baseline 5-HT(2A) binding in the brain and responses to noxious heat...... stimulation in a group of young healthy volunteers. Twenty-one healthy subjects underwent PET scanning with the 5-HT(2A) antagonist, [(18)F]altanserin. In addition, participants underwent a battery of pain tests using noxious heat stimulation to assess pain threshold, pain tolerance and response to short......-lasting phasic and long-lasting (7-minute) tonic painful stimulation. Significant positive correlations were found between tonic pain ratings and [(18)F]altanserin binding in orbitofrontal (r=0.66; p=0.005), medial inferior frontal (r=0.60; p=0.014), primary sensory-motor (r=0.61; p=0.012) and posterior...

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

    Directory of Open Access Journals (Sweden)

    Wenda Wu

    2015-01-01

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

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

    Science.gov (United States)

    Nazari, Leyla; Manstretta, Valentina; Rossi, Vittorio

    2016-04-01

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

  16. Plaque deposition dependent decrease in 5-HT2A serotonin receptor in AbetaPPswe/PS1dE9 amyloid overexpressing mice

    DEFF Research Database (Denmark)

    Holm, Peter; Ettrup, Anders; Klein, Anders B

    2010-01-01

    -HT2A receptor regulation in double transgenic AbetaPPswe/PS1dE9 mice which display excess production of Abeta and age-dependent increase in amyloid plaques. Three different age-groups, 4-month-old, 8- month-old, and 11-month-old were included in the study. [3H]-MDL100907, [3H]-escitalopram, and [11C...

  17. Role of IL-1 beta and 5-HT2 receptors in midbrain periaqueductal gray (PAG) in potentiating defensive rage behavior in cat.

    Science.gov (United States)

    Bhatt, Suresh; Bhatt, Rekha; Zalcman, Steven S; Siegel, Allan

    2008-02-01

    Feline defensive rage, a form of aggressive behavior that occurs in response to a threat can be elicited by electrical stimulation of the medial hypothalamus or midbrain periaqueductal gray (PAG). Our laboratory has recently begun a systematic examination of the role of cytokines in the regulation of rage and aggressive behavior. It was shown that the cytokine, interleukin-2 (IL-2), differentially modulates defensive rage when microinjected into the medial hypothalamus and PAG by acting through separate neurotransmitter systems. The present study sought to determine whether a similar relationship exists with respect to interleukin 1-beta (IL-1 beta), whose receptor activation in the medial hypothalamus potentiates defensive rage. Thus, the present study identified the effects of administration of IL-1 beta into the PAG upon defensive rage elicited from the medial hypothalamus. Microinjections of IL-1 beta into the dorsal PAG significantly facilitated defensive rage behavior elicited from the medial hypothalamus in a dose and time dependent manner. In addition, the facilitative effects of IL-1 beta were blocked by pre-treatment with anti-IL-1 beta receptor antibody, while IL-1 beta administration into the PAG had no effect upon predatory attack elicited from the lateral hypothalamus. The findings further demonstrated that IL-1 beta's effects were mediated through 5-HT(2) receptors since pretreatment with a 5-HT(2C) receptors antagonist blocked the facilitating effects of IL-1 beta. An extensive pattern of labeling of IL-1 beta and 5-HT(2C) receptors in the dorsal PAG supported these findings. The present study demonstrates that IL-beta in the dorsal PAG, similar to the medial hypothalamus, potentiates defensive rage behavior and is mediated through a 5-HT(2C) receptor mechanism.

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

    Directory of Open Access Journals (Sweden)

    Marie Elizabeth Gibbs

    2014-04-01

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

  19. 5-HT(2C) serotonin receptor blockade prevents tau protein hyperphosphorylation and corrects the defect in hippocampal synaptic plasticity caused by a combination of environmental stressors in mice.

    Science.gov (United States)

    Busceti, Carla Letizia; Di Pietro, Paola; Riozzi, Barbara; Traficante, Anna; Biagioni, Francesca; Nisticò, Robert; Fornai, Francesco; Battaglia, Giuseppe; Nicoletti, Ferdinando; Bruno, Valeria

    2015-09-01

    Exposure to multimodal sensory stressors is an everyday occurrence and sometimes becomes very intense, such as during rave parties or other recreational events. A growing body of evidence suggests that strong environmental stressors might cause neuronal dysfunction on their own in addition to their synergistic action with illicit drugs. Mice were exposed to a combination of physical and sensory stressors that are reminiscent of those encountered in a rave party. However, this is not a model of rave because it lacks the rewarding properties of rave. A 14-h exposure to environmental stressors caused an impairment of hippocampal long-term potentiation (LTP) and spatial memory, and an enhanced phosphorylation of tau protein in the CA1 and CA3 regions. These effects were transient and critically depended on the activation of 5-HT2C serotonin receptors, which are highly expressed in the CA1 region. Acute systemic injection of the selective 5-HT2C antagonist, RS-102,221 (2 mg/kg, i.p., 2 min prior the onset of stress), prevented tau hyperphosphorylation and also corrected the defects in hippocampal LTP and spatial memory. These findings suggest that passive exposure to a combination of physical and sensory stressors causes a reversible hippocampal dysfunction, which might compromise mechanisms of synaptic plasticity and spatial memory for a few days. Drugs that block 5-HT2C receptors might protect the hippocampus against the detrimental effect of environmental stressors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. MDMA-induced loss of parvalbumin interneurons within the dentate gyrus is mediated by 5HT2A and NMDA receptors.

    Science.gov (United States)

    Collins, Stuart A; Gudelsky, Gary A; Yamamoto, Bryan K

    2015-08-15

    MDMA is a widely abused psychostimulant which causes a rapid and robust release of the monoaminergic neurotransmitters dopamine and serotonin. Recently, it was shown that MDMA increases extracellular glutamate concentrations in the dorsal hippocampus, which is dependent on serotonin release and 5HT2A/2C receptor activation. The increased extracellular glutamate concentration coincides with a loss of parvalbumin-immunoreactive (PV-IR) interneurons of the dentate gyrus region. Given the known susceptibility of PV interneurons to excitotoxicity, we examined whether MDMA-induced increases in extracellular glutamate in the dentate gyrus are necessary for the loss of PV cells in rats. Extracellular glutamate concentrations increased in the dentate gyrus during systemic and local administration of MDMA. Administration of the NMDA receptor antagonist, MK-801, during systemic injections of MDMA, prevented the loss of PV-IR interneurons seen 10 days after MDMA exposure. Local administration of MDL100907, a selective 5HT2A receptor antagonist, prevented the increases in glutamate caused by reverse dialysis of MDMA directly into the dentate gyrus and prevented the reduction of PV-IR. These findings provide evidence that MDMA causes decreases in PV within the dentate gyrus through a 5HT2A receptor-mediated increase in glutamate and subsequent NMDA receptor activation. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Hall, H.; Wedel, I.

    1985-01-01

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

  2. Captodiamine, a putative antidepressant, enhances hypothalamic BDNF expression in vivo by synergistic 5-HT2c receptor antagonism and sigma-1 receptor agonism.

    Science.gov (United States)

    Ring, Rebecca M; Regan, Ciaran M

    2013-10-01

    The putative antidepressant captodiamine is a 5-HT2c receptor antagonist and agonist at sigma-1 and D3 dopamine receptors, exerts an anti-immobility action in the forced swim paradigm, and enhances dopamine turnover in the frontal cortex. Captodiamine has also been found to ameliorate stress-induced anhedonia, reduce the associated elevations of hypothalamic corticotrophin-releasing factor (CRF) and restore the reductions in hypothalamic BDNF expression. Here we demonstrate chronic administration of captodiamine to have no significant effect on hypothalamic CRF expression through sigma-1 receptor agonism; however, both sigma-1 receptor agonism or 5-HT2c receptor antagonism were necessary to enhance BDNF expression. Regulation of BDNF expression by captodiamine was associated with increased phosphorylation of transcription factor CREB and mediated through sigma-1 receptor agonism but blocked by 5-HT2c receptor antagonism. The existence of two separate signalling pathways was confirmed by immunolocalisation of each receptor to distinct cell populations in the paraventricular nucleus of the hypothalamus. Increased BDNF induced by captodiamine was also associated with enhanced expression of synapsin, but not PSD-95, suggesting induction of long-term structural plasticity between hypothalamic synapses. These unique features of captodiamine may contribute to its ability to ameliorate stress-induced anhedonia as the hypothalamus plays a prominent role in regulating HPA axis activity.

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

    Science.gov (United States)

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

    2002-08-30

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

  4. The effect of citalopram hydrobromide on 5-HT2A receptors in the impulsive-aggressive dog, as measured with 123I-5-I-R91150 SPECT

    International Nuclear Information System (INIS)

    Peremans, K.; Hoybergs, Y.; Gielen, I.; Audenaert, K.; Vervaet, M.; Heeringen, C. van; Otte, A.; Goethals, I.; Dierckx, R.; Blankaert, P.

    2005-01-01

    Involvement of the serotonergic system in impulsive aggression has been demonstrated in both human and animal studies. The purpose of the present study was to investigate the effect of citalopram hydrobromide (a selective serotonin re-uptake inhibitor) on the 5-HT 2A receptor and brain perfusion in impulsive-aggressive dogs by means of single-photon emission computed tomography. The binding index of the radioligand 123 I-5-I-R91150 was measured before and after treatment with citalopram hydrobromide in nine impulsive-aggressive dogs. Regional perfusion was measured with 99m Tc-ethyl cysteinate dimer (ECD). Behaviour was assessed before treatment and again after 6 weeks of treatment. A correlation was found between decreased binding and behavioural improvement in eight out of nine dogs. The 5-HT 2A receptor binding index was significantly reduced after citalopram hydrobromide treatment in all cortical regions but not in the subcortical area. None of the dogs displayed alterations in perfusion on the post-treatment scans. This study supports previous findings regarding the involvement of the serotonergic system in impulsive aggression in dogs in general. More specifically, the effect of treatment on the 5-HT 2A receptor binding index could be demonstrated and the decreased binding index correlated with behavioural improvement. (orig.)

  5. Serotonin 5-HT2C receptor-independent expression of hypothalamic NOR1, a novel modulator of food intake and energy balance, in mice

    Energy Technology Data Exchange (ETDEWEB)

    Nonogaki, Katsunori, E-mail: knonogaki-tky@umin.ac.jp [Center of Excellence, Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine (Japan); Department of Lifestyle Medicine, Biomedical Engineering Center, Tohoku University (Japan); Kaji, Takao [Department of Lifestyle Medicine, Biomedical Engineering Center, Tohoku University (Japan); Ohba, Yukie; Sumii, Makiko [Center of Excellence, Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine (Japan); Wakameda, Mamoru; Tamari, Tomohiro [Charles River Laboratories Japan, Inc. (Japan)

    2009-08-21

    NOR1, Nur77 and Nurr1 are orphan nuclear receptors and members of the NR4A subfamily. Here, we report that the expression of hypothalamic NOR1 was remarkably decreased in mildly obese {beta}-endorphin-deficient mice and obese db/db mice with the leptin receptor mutation, compared with age-matched wild-type mice, whereas there were no genotypic differences in the expression of hypothalamic Nur77 or Nurr1 in these animals. The injection of NOR1 siRNA oligonucleotide into the third cerebral ventricle significantly suppressed food intake and body weight in mice. On the other hand, the decreases in hypothalamic NOR1 expression were not found in non-obese 5-HT2C receptor-deficient mice. Moreover, systemic administration of m-chlorophenylpiperazine (mCPP), a 5-HT2C/1B receptor agonist, had no effect on hypothalamic NOR1 expression, while suppressing food intake in {beta}-endorphin-deficient mice. These findings suggest that 5-HT2C receptor-independent proopiomelanocortin-derived peptides regulate the expression of hypothalamic NOR1, which is a novel modulator of feeding behavior and energy balance.

  6. Serotonin 5-HT2C receptor-independent expression of hypothalamic NOR1, a novel modulator of food intake and energy balance, in mice

    International Nuclear Information System (INIS)

    Nonogaki, Katsunori; Kaji, Takao; Ohba, Yukie; Sumii, Makiko; Wakameda, Mamoru; Tamari, Tomohiro

    2009-01-01

    NOR1, Nur77 and Nurr1 are orphan nuclear receptors and members of the NR4A subfamily. Here, we report that the expression of hypothalamic NOR1 was remarkably decreased in mildly obese β-endorphin-deficient mice and obese db/db mice with the leptin receptor mutation, compared with age-matched wild-type mice, whereas there were no genotypic differences in the expression of hypothalamic Nur77 or Nurr1 in these animals. The injection of NOR1 siRNA oligonucleotide into the third cerebral ventricle significantly suppressed food intake and body weight in mice. On the other hand, the decreases in hypothalamic NOR1 expression were not found in non-obese 5-HT2C receptor-deficient mice. Moreover, systemic administration of m-chlorophenylpiperazine (mCPP), a 5-HT2C/1B receptor agonist, had no effect on hypothalamic NOR1 expression, while suppressing food intake in β-endorphin-deficient mice. These findings suggest that 5-HT2C receptor-independent proopiomelanocortin-derived peptides regulate the expression of hypothalamic NOR1, which is a novel modulator of feeding behavior and energy balance.

  7. Chronic SSRI stimulation of astrocytic 5-HT2B receptors change multiple gene expressions/editings and metabolism of glutamate, glucose and glycogen: a potential paradigm shift

    Directory of Open Access Journals (Sweden)

    Leif eHertz

    2015-02-01

    Full Text Available It is firmly believed that the mechanism of action of SSRIs in major depression is to inhibit the serotonin transporter, SERT, and increase extracellular concentration of serotonin. However, this undisputed observation does not prove that SERT inhibition is the mechanism, let alone the only mechanism, by which SSRI’s exert their therapeutic effects. It has recently been demonstrated that 5-HT2B receptor stimulation is needed for the antidepressant effect of fluoxetine in vivo. The ability of all 5 currently used SSRIs to stimulate the 5-HT2B receptor equipotentially incultured astrocyteshas been known for several years,and increasing evidence has shown the importance of astrocytes and astrocyte-neuronal interactions for neuroplasticity and complex brain activity. This paper reviews acute and chronic effects of 5-HT2B receptor stimulation in cultured astrocytes and in astrocytes freshly isolated from brains of mice treated with fluoxetine for 14 daystogether with effects ofanti-depressant therapy on turnover of glutamate and GABA and metabolism of glucose and glycogen. It is suggested that these events are causally related to the mechanism of action of SSRIs and of interest for development of newer antidepressant drugs.

  8. Joint research using small tokamaks

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  9. Joint research using small tokamaks

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  10. Advanced commercial tokamak study

    International Nuclear Information System (INIS)

    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

  11. Evidence for a role of 5-HT2C receptors in the motor aspects of performance, but not the efficacy of food reinforcers, in a progressive ratio schedule.

    Science.gov (United States)

    Bezzina, G; Body, S; Cheung, T H C; Hampson, C L; Bradshaw, C M; Glennon, J C; Szabadi, E

    2015-02-01

    5-Hydroxytryptamine2C (5-HT2C) receptor agonists reduce the breakpoint in progressive ratio schedules of reinforcement, an effect that has been attributed to a decrease of the efficacy of positive reinforcers. However, a reduction of the breakpoint may also reflect motor impairment. Mathematical models can help to differentiate between these processes. The effects of the 5-HT2C receptor agonist Ro-600175 ((αS)-6-chloro-5-fluoro-α-methyl-1H-indole-1-ethanamine) and the non-selective 5-HT receptor agonist 1-(m-chlorophenyl)piperazine (mCPP) on rats' performance on a progressive ratio schedule maintained by food pellet reinforcers were assessed using a model derived from Killeen's Behav Brain Sci 17:105-172, 1994 general theory of schedule-controlled behaviour, 'mathematical principles of reinforcement'. Rats were trained under the progressive ratio schedule, and running and overall response rates in successive ratios were analysed using the model. The effects of the agonists on estimates of the model's parameters, and the sensitivity of these effects to selective antagonists, were examined. Ro-600175 and mCPP reduced the breakpoint. Neither agonist significantly affected a (the parameter expressing incentive value), but both agonists increased δ (the parameter expressing minimum response time). The effects of both agonists could be attenuated by the selective 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-N-{6-[(2-methylpyridin-3-yl)oxy]pyridin-3-yl}indoline-1-carboxamide). The effect of mCPP was not altered by isamoltane, a selective 5-HT1B receptor antagonist, or MDL-100907 ((±)2,3-dimethoxyphenyl-1-(2-(4-piperidine)methanol)), a selective 5-HT2A receptor antagonist. The results are consistent with the hypothesis that the effect of the 5-HT2C receptor agonists on progressive ratio schedule performance is mediated by an impairment of motor capacity rather than by a reduction of the incentive value of the food reinforcer.

  12. Behavioral Effects of Systemic, Infralimbic and Prelimbic Injections of a Serotonin 5-HT2A Antagonist in Carioca High- and Low-Conditioned Freezing Rats

    Directory of Open Access Journals (Sweden)

    Laura A. León

    2017-07-01

    Full Text Available The role of serotonin (5-hydroxytryptamine [5-HT] and 5-HT2A receptors in anxiety has been extensively studied, mostly without considering individual differences in trait anxiety. Our laboratory developed two lines of animals that are bred for high and low freezing responses to contextual cues that are previously associated with footshock (Carioca High-conditioned Freezing [CHF] and Carioca Low-conditioned Freezing [CLF]. The present study investigated whether ketanserin, a preferential 5-HT2A receptor blocker, exerts distinct anxiety-like profiles in these two lines of animals. In the first experiment, the animals received a systemic injection of ketanserin and were exposed to the elevated plus maze (EPM. In the second experiment, these two lines of animals received microinjections of ketanserin in the infralimbic (IL and prelimbic (PL cortices and were exposed to either the EPM or a contextual fear conditioning paradigm. The two rat lines exhibited bidirectional effects on anxiety-like behavior in the EPM and opposite responses to ketanserin. Both systemic and intra-IL cortex injections of ketanserin exerted anxiolytic-like effects in CHF rats but anxiogenic-like effects in CLF rats. Microinjections of ketanserin in the PL cortex also exerted anxiolytic-like effects in CHF rats but had no effect in CLF rats. These results suggest that the behavioral effects of 5-HT2A receptor antagonism might depend on genetic variability associated with baseline reactions to threatening situations and 5-HT2A receptor expression in the IL and PL cortices.Highlights-CHF and CLF rats are two bidirectional lines that are based on contextual fear conditioning.-CHF rats have a more “anxious” phenotype than CLF rats in the EPM.-The 5-HT2A receptor antagonist ketanserin had opposite behavioral effects in CHF and CLF rats.-Systemic and IL injections either decreased (CHF or increased (CLF anxiety-like behavior.-PL injections either decreased (CHF anxiety

  13. Design, Synthesis, and Pharmacological Characterization of N- and O-Substituted 5,6,7,8-Tetrahydro-4H-isoxazolo[4,5-d]azepin-3-ol Analogues: Novel 5-HT2A/5-HT2C Receptor Agonists with Pro-Cognitive Properties

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Plath, Niels; Pedersen, Martin Holst Friborg

    2013-01-01

    to be selective for the two receptors. Administration of 3d substantially improved the cognitive performance of mice in a place recognition Y-maze model, an effect fully reversible by coadministration of the selective 5-HT2C antagonist SB242084. In conclusion, as novel bioavailable cognitive enhancers that most...

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

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  15. Advanced statistics for tokamak transport colinearity and tokamak to tokamak variation

    International Nuclear Information System (INIS)

    Riedel, K.S.

    1989-03-01

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  17. Microwave Tokamak Experiment

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    The Microwave Tokamak Experiment, now under construction at the Laboratory, will use microwave heating from a free-electron laser. The intense microwave pulses will be injected into the tokamak to realize several goals, including a demonstration of the effects of localized heat deposition within magnetically confined plasma, a better understanding of energy confinement in tokamaks, and use of the new free-electron laser technology for plasma heating. The experiment, soon to be operational, provides an opportunity to study dense plasmas heated by powers unprecedented in the electron-cyclotron frequency range required by the especially high magnetic fields used with the MTX and needed for reactors. 1 references, 5 figures, 3 tables

  18. Texas Experimental Tokamak

    International Nuclear Information System (INIS)

    Wootton, A.J.

    1993-04-01

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

  19. Magnetic ''islandography'' in tokamaks

    International Nuclear Information System (INIS)

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

    1978-09-01

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

  20. Accelerator technology in tokamaks

    International Nuclear Information System (INIS)

    Kustom, R.L.

    1977-01-01

    This article presents the similarities in the technology required for high energy accelerators and tokamak fusion devices. The tokamak devices and R and D programs described in the text represent only a fraction of the total fusion program. The technological barriers to producing successful, economical tokamak fusion power plants are as many as the plasma physics problems to be overcome. With the present emphasis on energy problems in this country and elsewhere, it is very likely that fusion technology related R and D programs will vigorously continue; and since high energy accelerator technology has so much in common with fusion technology, more scientists from the accelerator community are likely to be attracted to fusion problems

  1. ARIES tokamak reactor study

    International Nuclear Information System (INIS)

    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

  2. Internal disruption in tokamaks

    International Nuclear Information System (INIS)

    Kuvshinov, B.N.; Savrukhin, P.V.

    1990-01-01

    A review of results of experimental and theoretical investigations of internal disruption in tokamaks is given. Specific features of various types of saw-tooth oscillations are described and their classification is performed. Theoretical models of the process of development of internal disruption instability are discussed. Effect of internal disruption on parameters of plasma, confined in tokamak, is considered. Scalings of period and amplitude of saw-tooth oscillations, as well as version radius are presented. Different methods for stabilizing instability of internal disruption are described

  3. Overview of Tokamak Results

    International Nuclear Information System (INIS)

    Unterberg, Bernhard; Samm, Ulrich

    2004-01-01

    An overview is given of recent results obtained in tokamak devices. We introduce basic confinement scenarios as L-mode, H-mode and plasmas with an internal transport barrier and discuss methods for profile control. Important findings in DT-experiments at JET as α-particle heating are described. Methods for power exhaust like plasma regimes with a radiating mantle and radiative divertor scenarios are discussed. The overall impact of plasma edge conditions on the general plasma performance in tokamaks is illustrated by describing the impact of wall conditions on confinement and the edge operational diagram of H-mode plasmas

  4. Internal disruptions in tokamaks

    International Nuclear Information System (INIS)

    Kuvshinov, B.N.; Savrukhin, P.V.

    1990-01-01

    Experimental and theoretical studies of the phenomenon of internal disruptions in tokamaks are reviewed. A classification scheme is introduced and the features of different types of sawtooth oscillations are described. A theoretical model for the development of the internal disruption instability is discussed. The effect of internal disruptions on the parameters of plasma confined in tokamaks is discussed. Scaling laws for the period and amplitude of sawtooth oscillations, as well as for the inversion radius, are presented. Different methods of stabilizing the internal disruption instability are described

  5. High beta tokamaks

    International Nuclear Information System (INIS)

    Dory, R.A.; Berger, D.P.; Charlton, L.A.; Hogan, J.T.; Munro, J.K.; Nelson, D.B.; Peng, Y.K.M.; Sigmar, D.J.; Strickler, D.J.

    1978-01-01

    MHD equilibrium, stability, and transport calculations are made to study the accessibility and behavior of ''high beta'' tokamak plasmas in the range β approximately 5 to 15 percent. For next generation devices, beta values of at least 8 percent appear to be accessible and stable if there is a conducting surface nearby

  6. Sawtooth phenomena in tokamaks

    International Nuclear Information System (INIS)

    Kuvshinov, B.N.; Savrukhin, P.V.

    1989-01-01

    A review of experimental and theoretical investigaions of sawtooth phenomena in tokamaks is presented. Different types of sawtooth oscillations, scaling laws and methods of interanl disruption stabilization are described. Theoretical models of the sawtooth instability are discussed. 122 refs.; 4 tabs

  7. Reconnection in tokamaks

    International Nuclear Information System (INIS)

    Pare, V.K.

    1983-01-01

    Calculations with several different computer codes based on the resistive MHD equations have shown that (m = 1, n = 1) tearing modes in tokamak plasmas grow by magnetic reconnection. The observable behavior predicted by the codes has been confirmed in detail from the waveforms of signals from x-ray detectors and recently by x-ray tomographic imaging

  8. Research using small tokamaks

    International Nuclear Information System (INIS)

    1993-01-01

    This document consists of a collection of papers presented at the IAEA Technical Committee Meeting on Research Using Small Tokamaks. It contains 22 papers on a wide variety of research aspects, including diagnostics, design, transport, equilibrium, stability, and confinement. Some of these papers are devoted to other concepts (stellarators, compact tori). Refs, figs and tabs

  9. Research using small tokamaks

    International Nuclear Information System (INIS)

    1991-01-01

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

  10. Compact tokamak reactors

    International Nuclear Information System (INIS)

    Wootton, A.J.; Wiley, J.C.; Edmonds, P.H.; Ross, D.W.

    1997-01-01

    The possible use of tokamaks for thermonuclear power plants is discussed, in particular tokamaks with low aspect ratio and copper toroidal field coils. Three approaches are presented. First, the existing literature is reviewed and summarized. Second, using simple analytic estimates, the size of the smallest tokamak to produce an ignited plasma is derived. This steady state energy balance analysis is then extended to determine the smallest tokamaks power plant, by including the power required to drive the toroidal field and by considering two extremes of plasma current drive efficiency. Third, the analytic results are augmented by a numerical calculation that permits arbitrary plasma current drive efficiency and different confinement scaling relationships. Throughout, the importance of various restrictions is emphasized, in particular plasma current drive efficiency, plasma confinement, plasma safety factor, plasma elongation, plasma beta, neutron wall loading, blanket availability and recirculation of electric power. The latest published reactor studies show little advantage in using low aspect ratios to obtain a more compact device (and a low cost of electricity) unless either remarkably high efficiency plasma current drive and low safety factor are combined, or unless confinement (the H factor), the permissible elongation and the permissible neutron wall loading increase as the aspect ratio is reduced. These results are reproduced with the analytic model. (author). 22 refs, 3 figs

  11. Texas Experimental Tokamak

    International Nuclear Information System (INIS)

    Wootton, A.J.

    1990-04-01

    This paper discusses the following work on the text tokamak: data systems; particle confinement; impurity transport; plasma rotation; runaway electrons; electron cyclotron heating; FIR system; transient transport; internal turbulence; edge turbulence; ion temperature; EML experiments; impurity pellet experiments; MHD experiments and analysis; TEXT Upgrade; and Upgrade diagnostics

  12. 5-HT2 and 5-HT7 receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons

    Directory of Open Access Journals (Sweden)

    Urszula eSlawinska

    2014-08-01

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

  13. Reproducibility of 5-HT2A receptor measurements and sample size estimations with [18F]altanserin PET using a bolus/infusion approach

    International Nuclear Information System (INIS)

    Haugboel, Steven; Pinborg, Lars H.; Arfan, Haroon M.; Froekjaer, Vibe M.; Svarer, Claus; Knudsen, Gitte M.; Madsen, Jacob; Dyrby, Tim B.

    2007-01-01

    To determine the reproducibility of measurements of brain 5-HT 2A receptors with an [ 18 F]altanserin PET bolus/infusion approach. Further, to estimate the sample size needed to detect regional differences between two groups and, finally, to evaluate how partial volume correction affects reproducibility and the required sample size. For assessment of the variability, six subjects were investigated with [ 18 F]altanserin PET twice, at an interval of less than 2 weeks. The sample size required to detect a 20% difference was estimated from [ 18 F]altanserin PET studies in 84 healthy subjects. Regions of interest were automatically delineated on co-registered MR and PET images. In cortical brain regions with a high density of 5-HT 2A receptors, the outcome parameter (binding potential, BP 1 ) showed high reproducibility, with a median difference between the two group measurements of 6% (range 5-12%), whereas in regions with a low receptor density, BP 1 reproducibility was lower, with a median difference of 17% (range 11-39%). Partial volume correction reduced the variability in the sample considerably. The sample size required to detect a 20% difference in brain regions with high receptor density is approximately 27, whereas for low receptor binding regions the required sample size is substantially higher. This study demonstrates that [ 18 F]altanserin PET with a bolus/infusion design has very low variability, particularly in larger brain regions with high 5-HT 2A receptor density. Moreover, partial volume correction considerably reduces the sample size required to detect regional changes between groups. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Yvonne Couch

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

  15. Pharmacological Characterization of H05, a Novel Serotonin and Noradrenaline Reuptake Inhibitor with Moderate 5-HT2A Antagonist Activity for the Treatment of Depression.

    Science.gov (United States)

    Xu, Xiangqing; Wei, Yaqin; Guo, Qiang; Zhao, Song; Liu, Zhiqiang; Xiao, Ting; Liu, Yani; Qiu, Yinli; Hou, Yuanyuan; Zhang, Guisen; Wang, KeWei

    2018-06-01

    Multitarget antidepressants selectively inhibiting monoaminergic transporters and 5-hydroxytryptamine (5-HT) 2A receptor have demonstrated higher efficacy and fewer side effects than selective serotonin reuptake inhibitors. In the present study, we synthesized a series of novel 3-(benzo[d][1,3]dioxol-4-yloxy)-3-arylpropyl amine derivatives, among which compound H05 was identified as a lead, exhibiting potent inhibitory effects on both serotonin ( K i = 4.81 nM) and norepinephrine (NE) ( K i = 6.72 nM) transporters and moderate 5-HT 2A antagonist activity (IC 50 = 60.37 nM). H05 was able to dose-dependently reduce the immobility duration in mouse forced swimming test and tail suspension test, with the minimal effective doses lower than those of duloxetine, and showed no stimulatory effect on locomotor activity. The administration of H05 (5, 10, and 20 mg/kg, by mouth) significantly shortened the immobility time of adrenocorticotropin-treated rats that serve as a model of treatment-resistant depression, whereas imipramine (30 mg/kg, by mouth) and duloxetine (30 mg/kg, by mouth) showed no obvious effects. Chronic treatment with H05 reversed the depressive-like behaviors in a rat model of chronic unpredictable mild stress and a mouse model of corticosterone-induced depression. Microdialysis analysis revealed that the administration of H05 at either 10 or 20 mg/kg increased the release of 5-HT and NE from the frontal cortex. The pharmacokinetic (PK) and brain penetration analyses suggest that H05 has favorable PK properties with good blood-brain penetration ability. Therefore, it can be concluded that H05, a novel serotonin and NE reuptake inhibitor with 5-HT 2A antagonist activity, possesses efficacious activity in the preclinical models of depression and treatment-resistant depression, and it may warrant further evaluation for clinical development. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

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

    Science.gov (United States)

    Kaspersen, Helge; Agmo, Anders

    2012-03-01

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

  17. The 5-HT2C receptor agonist lorcaserin reduces nicotine self-administration, discrimination, and reinstatement: relationship to feeding behavior and impulse control.

    Science.gov (United States)

    Higgins, Guy A; Silenieks, Leo B; Rossmann, Anne; Rizos, Zoe; Noble, Kevin; Soko, Ashlie D; Fletcher, Paul J

    2012-04-01

    Lorcaserin ((1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl) is a selective 5-HT(2C) receptor agonist with clinical efficacy in phase-III obesity trials. Based on evidence that this drug class also affects behaviors motivated by drug reinforcement, we compared the effect of lorcaserin on behavior maintained by food and nicotine reinforcement, as well as the stimulant and discriminative stimulus properties of nicotine in the rat. Acutely administered lorcaserin (0.3-3 mg/kg, subcutaneous (SC)) dose dependently reduced feeding induced by 22-h food deprivation or palatability. Effects up to 1 mg/kg were consistent with a specific effect on feeding motivation. Lorcaserin (0.6-1 mg/kg, SC) reduced operant responding for food on progressive and fixed ratio schedules of reinforcement. In this dose range lorcaserin also reversed the motor stimulant effect of nicotine, reduced intravenous self-administration of nicotine, and attenuated the nicotine cue in rats trained to discriminate nicotine from saline. Lorcaserin also reduced the reinstatement of nicotine-seeking behavior elicited by a compound cue comprising a nicotine prime and conditioned stimulus previously paired with nicotine reinforcement. Lorcaserin did not reinstate nicotine-seeking behavior or substitute for a nicotine cue. Finally, lorcaserin (0.3-1 mg/kg) reduced nicotine-induced increases in anticipatory responding, a measure of impulsive action, in rats performing the five-choice serial reaction time task. Importantly, these results indicate that lorcaserin, and likely other selective 5-HT(2C) receptor agonists, similarly affect both food- and nicotine-motivated behaviors, and nicotine-induced impulsivity. Collectively, these findings highlight a therapeutic potential for 5-HT(2C) agonists such as lorcaserin beyond obesity into addictive behaviors, such as nicotine dependence.

  18. Tokamaks (Second Edition)

    Energy Technology Data Exchange (ETDEWEB)

    Stott, Peter [JET, UK (United Kingdom)

    1998-10-01

    The first edition of John Wesson's book on tokamaks, published in 1987, established itself as essential reading for researchers in the field of magnetic confinement fusion: it was an excellent introduction for students to tokamak physics and also a valuable reference work for the more experienced. The second edition, published in 1997, has been completely rewritten and substantially enlarged (680 pages compared with 300). The new edition maintains the aim of providing a simple introduction to basic tokamak physics, but also includes discussion of the substantial advances in fusion research during the past decade. The new book, like its predecessor, is well written and commendable for its clarity and accuracy. In fact many of the chapters are written by a series of co-authors bringing the benefits of a wide range of expertise but, by careful editing, Wesson has maintained a uniformity of style and presentation. The chapter headings and coverage for the most part remain the same - but are expanded considerably and brought up to date. The most substantial change is that the single concluding chapter in the first edition on 'Experiments' has been replaced by three chapters: 'Tokamak experiments' which deals with some of the earlier key experiments plus a selection of recent small and medium-sized devices, 'Large experiments' which gives an excellent summary of the main results from the four large tokamaks - TFTR, JET, JT60/JT60U and DIII-D, and 'The future' which gives a very short (possibly too short in my opinion) account of reactors and ITER. This is an excellent book, which I strongly recommend should have a place - on the desk rather than in the bookshelf - of researchers in magnetic confinement fusion. (book review)

  19. Tokamaks (Second Edition)

    International Nuclear Information System (INIS)

    Stott, Peter

    1998-01-01

    The first edition of John Wesson's book on tokamaks, published in 1987, established itself as essential reading for researchers in the field of magnetic confinement fusion: it was an excellent introduction for students to tokamak physics and also a valuable reference work for the more experienced. The second edition, published in 1997, has been completely rewritten and substantially enlarged (680 pages compared with 300). The new edition maintains the aim of providing a simple introduction to basic tokamak physics, but also includes discussion of the substantial advances in fusion research during the past decade. The new book, like its predecessor, is well written and commendable for its clarity and accuracy. In fact many of the chapters are written by a series of co-authors bringing the benefits of a wide range of expertise but, by careful editing, Wesson has maintained a uniformity of style and presentation. The chapter headings and coverage for the most part remain the same - but are expanded considerably and brought up to date. The most substantial change is that the single concluding chapter in the first edition on 'Experiments' has been replaced by three chapters: 'Tokamak experiments' which deals with some of the earlier key experiments plus a selection of recent small and medium-sized devices, 'Large experiments' which gives an excellent summary of the main results from the four large tokamaks - TFTR, JET, JT60/JT60U and DIII-D, and 'The future' which gives a very short (possibly too short in my opinion) account of reactors and ITER. This is an excellent book, which I strongly recommend should have a place - on the desk rather than in the bookshelf - of researchers in magnetic confinement fusion. (book review)

  20. Direct comparison of [18F]MH.MZ and [18F]altanserin for 5-HT2A receptor imaging with PET

    DEFF Research Database (Denmark)

    Hansen, Hanne Demant; Ettrup, Anders; Herth, Matthias Manfred

    2013-01-01

    ]altanserin was blocked by ketanserin supporting that both radioligands bind to 5-HT(2A) receptors in the pig brain. In the HPLC analysis of pig plasma, [(18) F]MH.MZ displayed a fast and reproducible metabolism resulting in hydrophilic radiometabolites only whereas the metabolic profile of [(18) F]altanserin as expected......]altanserin were investigated in Danish Landrace pigs by brain PET scanning at baseline and after i.v. administration of blocking doses of ketanserin. Full arterial input function and HPLC analysis allowed for tissue-compartment kinetic modelling of PET data. In vitro autoradiography showed high binding...

  1. Loss of GluN2D subunit results in social recognition deficit, social stress, 5-HT2C receptor dysfunction, and anhedonia in mice.

    Science.gov (United States)

    Yamamoto, Hideko; Kamegaya, Etsuko; Hagino, Yoko; Takamatsu, Yukio; Sawada, Wakako; Matsuzawa, Maaya; Ide, Soichiro; Yamamoto, Toshifumi; Mishina, Masayoshi; Ikeda, Kazutaka

    2017-01-01

    The N-methyl-d-aspartate (NMDA) receptor channel is involved in various physiological functions, including learning and memory. The GluN2D subunit of the NMDA receptor has low expression in the mature brain, and its role is not fully understood. In the present study, the effects of GluN2D subunit deficiency on emotional and cognitive function were investigated in GluN2D knockout (KO) mice. We found a reduction of motility (i.e., a depressive-like state) in the tail suspension test and a reduction of sucrose preference (i.e., an anhedonic state) in GluN2D KO mice that were group-housed with littermates. Despite apparently normal olfactory function and social interaction, GluN2D KO mice exhibited a decrease in preference for social novelty, suggesting a deficit in social recognition or memory. Golgi-Cox staining revealed a reduction of the complexity of dendritic trees in the accessory olfactory bulb in GluN2D KO mice, suggesting a deficit in pheromone processing pathway activation, which modulates social recognition. The deficit in social recognition may result in social stress in GluN2D KO mice. Isolation housing is a procedure that has been shown to reduce stress in mice. Interestingly, 3-week isolation and treatment with agomelatine or the 5-hydroxytryptamine-2C (5-HT 2C ) receptor antagonist SB242084 reversed the anhedonic-like state in GluN2D KO mice. In contrast, treatment with the 5-HT 2C receptor agonist CP809101 induced depressive- and anhedonic-like states in isolated GluN2D KO mice. These results suggest that social stress that is caused by a deficit in social recognition desensitizes 5-HT 2c receptors, followed by an anhedonic- and depressive-like state, in GluN2D KO mice. The GluN2D subunit of the NMDA receptor appears to be important for the recognition of individuals and development of normal emotionality in mice. 5-HT 2C receptor antagonism may be a therapeutic target for treating social stress-induced anhedonia. This article is part of the Special

  2. Yokukansan, a traditional Japanese herbal medicine, enhances the anxiolytic effect of fluvoxamine and reduces cortical 5-HT2A receptor expression in mice.

    Science.gov (United States)

    Ohno, Rintaro; Miyagishi, Hiroko; Tsuji, Minoru; Saito, Atsumi; Miyagawa, Kazuya; Kurokawa, Kazuhiro; Takeda, Hiroshi

    2018-04-24

    Yokukansan is a traditional Japanese herbal medicine that has been approved in Japan as a remedy for neurosis, insomnia, and irritability in children. It has also been reported to improve behavioral and psychological symptoms in patients with various forms of dementia. To evaluate the usefulness of co-treatment with an antidepressant and an herbal medicine in the psychiatric field, the current study examined the effect of yokukansan on the anxiolytic-like effect of fluvoxamine in mice. The anxiolytic-like effect in mice was estimated by the contextual fear conditioning paradigm. Contextual fear conditioning consisted of two sessions, i.e., day 1 for the conditioning session and day 2 for the test session. The expression levels of 5-HT 1A and 5-HT 2A receptor in the mouse brain regions were quantified by western blot analysis. A single administration of fluvoxamine (5-20 mg/kg, i.p.) before the test session dose-dependently and significantly suppressed freezing behavior in mice. In the combination study, a sub-effective dose of fluvoxamine (5 mg/kg, i.p.) significantly suppressed freezing behavior in mice that had been repeatedly pretreated with yokukansan (0.3 and 1 g/kg, p.o.) once a day for 6 days after the conditioning session. Western blot analysis revealed that the expression level of 5-HT 2A receptor was specifically decreased in the prefrontal cortex of mice that had been administered yokukansan and fluvoxamine. Furthermore, microinjection of the 5-HT 2A receptor antagonist ketanserin (5 nmol/mouse) into the prefrontal cortex significantly suppressed freezing behavior. The present findings indicate that repeated treatment with yokukansan synergistically enhances the anxiolytic-like effect of fluvoxamine in the contextual fear conditioning paradigm in mice in conjunction with a decrease in 5-HT 2A receptor-mediated signaling in the prefrontal cortex. Therefore, combination therapy with fluvoxamine and yokukansan may be beneficial for the treatment of

  3. Pharmacokinetics and brain distribution in non human primate of R(-)[123I]DOI, A 5HT2A/2C serotonin agonist

    International Nuclear Information System (INIS)

    Zea-Ponce, Yolanda; Kegeles, Lawrence S.; Guo, Ningning; Raskin, Leonid; Bakthavachalam, Venkatesalu; Laruelle, Marc

    2002-01-01

    Our goal was to synthesize with high specific activity R(-)-1-(2,5-Dimethoxy-4-[ 123 I]iodophenyl)-2-aminopropane [R(-)[ 123 I]DOI], an in vitro potent and selective 5-HT 2A/2C serotonin agonist, and study in vivo its plasma pharmacokinetics and brain distribution in baboon by SPECT. The purpose was to evaluate this radiotracer as a potential tool in discerning the role of the agonist high affinity state of 5-HT 2 receptors in depression and other neurological disorders. The radiotracer was prepared by electrophilic radioiodination of the N-trifluoroacetyl precursor of R(-)-1-(2,5-Dimethoxyphenyl)-2-aminopropane [R(-)DMA-TFA] with high-purity sodium [ 123 I]iodide in the presence of chloramine-T, followed by amino deprotection with KOH in isopropanol (labeling yield: 73%, radiochemical yield: 62%, radiochemical purity: 99%). In vivo studies in baboon showed high accumulation of radioactivity in thalamus, the frontoparietal cortex, temporal, occipital and the striatum regions, with slightly lower accumulation in the midbrain and cerebellum. Ketanserin did not displaced the radioactivity in any of these brain regions. Plasma metabolite analysis was performed using methanol protein precipitation, the methanol fractions contained from 68% to 92% of the mixture of a labeled metabolite and parent compound. The recovery coefficient of unmetabolized R(-)[ 123 I]DOI was 68%. The percent parent compound present in the extracted fraction, measured by HPLC, decreased gradually with time from 99.8% to 0.3% still present after 4.7 hours post injection whereas the percentage of the only one detected metabolite increased conversely. Free fraction determination (f 1 ), was 31±0.9% (n=3). For comparison purposes, ex-vivo brain distribution, displacement and metabolite analysis was also carried out in rodents. Although R(-)[ 123 I]DOI displayed good brain uptake and localized in serotonergic areas of the brain, its target to non target ratio and its insensitivity to ketanserin

  4. Present status of Tokamak research

    International Nuclear Information System (INIS)

    Basu, Jayanta

    1991-01-01

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

  5. Large Aspect Ratio Tokamak Study

    International Nuclear Information System (INIS)

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

    1980-06-01

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

  6. Association of 5-HT2C (rs3813929) and UCP3 (rs1800849) gene polymorphisms with type 2 diabetes in obese women candidates for bariatric surgery.

    Science.gov (United States)

    Schnor, Noa Pereira Prada; Verlengia, Rozangela; Novais, Patrícia Fátima Sousa; Crisp, Alex Harley; Leite, Celso Vieira de Souza; Rasera-Junior, Irineu; Oliveira, Maria Rita Marques de

    2017-01-01

    Obesity can cause systemic arterial hypertension (SAH) and type 2 diabetes mellitus (DM2) factor that is also influenced by genetic variability. The present study aims to investigate the association between gene polymorphisms related with obesity on the prevalence of SAH and DM2 in the preoperative period and 1 year after Roux-en-Y gastric bypass surgery. In total, 351 obese women in a Brazilian cohort completed the study. The clinical diagnosis of SAH and DM2 was monitored from medical records. Twelve gene polymorphisms (rs26802; rs572169; rs7799039; rs1137101; rs3813929; rs659366; rs660339; rs1800849; rs7498665; rs35874116; rs9701796; and rs9939609) were determined using real-time polymerase chain reaction and TaqMan assay. In the preoperative period, prevalence of SAH and DM2 was 57% and 22%, respectively. One year postoperatively, 86.8% subjects had remission of DM2 and 99.5% had control of SAH. Subjects with T allele from the serotonin receptor gene (5-HT2C, rs3813929) had five times greater chance of DM2, and the CC genotype from uncoupling protein 3 gene (UCP3, rs1800849) had three times greater chance in the preoperative period. These findings indicate that polymorphisms rs3813929 and rs1800849 from 5-HT2C and UCP3 genes were related to DM2 prevalence among the Brazilian obese women candidates for bariatric surgery.

  7. Membrane cholesterol effect on the 5-HT2A receptor: Insights into the lipid-induced modulation of an antipsychotic drug target.

    Science.gov (United States)

    Ramírez-Anguita, Juan Manuel; Rodríguez-Espigares, Ismael; Guixà-González, Ramon; Bruno, Agostino; Torrens-Fontanals, Mariona; Varela-Rial, Alejandro; Selent, Jana

    2018-01-01

    The serotonin 5-hydroxytryptamine 2A (5-HT 2A ) receptor is a G-protein-coupled receptor (GPCR) relevant for the treatment of CNS disorders. In this regard, neuronal membrane composition in the brain plays a crucial role in the modulation of the receptor functioning. Since cholesterol is an essential component of neuronal membranes, we have studied its effect on the 5-HT 2A receptor dynamics through all-atom MD simulations. We find that the presence of cholesterol in the membrane increases receptor conformational variability in most receptor segments. Importantly, detailed structural analysis indicates that conformational variability goes along with the destabilization of hydrogen bonding networks not only within the receptor but also between receptor and lipids. In addition to increased conformational variability, we also find receptor segments with reduced variability. Our analysis suggests that this increased stabilization is the result of stabilizing effects of tightly bound cholesterol molecules to the receptor surface. Our finding contributes to a better understanding of membrane-induced alterations of receptor dynamics and points to cholesterol-induced stabilizing and destabilizing effects on the conformational variability of GPCRs. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  8. Pharmacological evaluation of halogenated and non-halogenated arylpiperazin-1-yl-ethyl-benzimidazoles as D(2) and 5-HT(2A) receptor ligands.

    Science.gov (United States)

    Tomić, Mirko; Vasković, Djurdjica; Tovilović, Gordana; Andrić, Deana; Penjišević, Jelena; Kostić-Rajačić, Sladjana

    2011-05-01

    Five groups of previously synthesized and initially screened non-substituted and 4-halogenated arylpiperazin-1-yl-ethyl-benzimidazoles were estimated for their in-vitro binding affinities at the rat D(2) , 5-HT(2A) , and α(1) -adrenergic receptors. Among all these compounds, 2-methoxyphenyl and 2-chlorophenyl piperazines demonstrate the highest affinities for the tested receptors. The effects of 4-halogenation of benzimidazoles reveal that substitution with bromine may greatly increase the affinity of the compounds for the studied receptors, while the effect of substitution with chlorine is less remarkable. Most of the tested components show 5-HT(2A)/D(2) pK(i) binding ratios slightly above or less than 1, while only 4-chloro-6-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-1H-benzimidazole expresses an appropriate higher binding ratio (1.14), which was indicated for atypical neuroleptics. This compound exhibits a non-cataleptic action in rats and prevents d-amphetamine-induced hyperlocomotion in mice, which suggest its atypical antipsychotic potency. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 18F-labeling and evaluation of novel MDL 100907 derivatives as potential 5-HT2A antagonists for molecular imaging

    DEFF Research Database (Denmark)

    Debus, Fabian; Herth, Matthias Manfred; Piel, Markus

    2010-01-01

    ]tracers with a purity >96% and a typical specific activity of 25-35 GBq/mumol. Autoradiographic images of (R)-[(18)F]MH.MZ (5) and [(18)F]DD-1 (4) showed excellent visualization and selectivity of the 5-HT2A receptor for (R)-[(18)F]MH.MZ and less specific binding for [(18)F]DD-1. The binding potential (BP) of (R)-[(18......, equal levels of specific activities were used. High uptake could be demonstrated in cortex regions. CONCLUSION: Labeling of both novel tracers was carried out in high RCY. Autoradiography revealed (R)-[(18)F]MH.MZ as a very selective and affine 5-HT2A tracer (K(i)=0.72 nM), whereas [(18)F]DD-1 showed...... no reasonable distribution pattern on autoradiographic sections. Moreover, results from microPET scans of (R)-[(18)F]MH.MZ hint on improved molecular imaging characteristics compared with those of [(18)F]MH.MZ. Therefore, (R)-[(18)F]MH.MZ appears to be a highly potent and selective serotonergic PET ligand...

  10. 5-HT2C receptors in the BNST are necessary for the enhancement of fear learning by selective serotonin reuptake inhibitors.

    Science.gov (United States)

    Pelrine, Eliza; Pasik, Sara Diana; Bayat, Leyla; Goldschmiedt, Debora; Bauer, Elizabeth P

    2016-12-01

    Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed to treat anxiety and depression, yet they paradoxically increase anxiety during initial treatment. Acute administration of these drugs prior to learning can also enhance Pavlovian cued fear conditioning. This potentiation has been previously reported to depend upon the bed nucleus of the stria terminalis (BNST). Here, using temporary inactivation, we confirmed that the BNST is not necessary for the acquisition of cued or contextual fear memory. Systemic administration of the SSRI citalopram prior to fear conditioning led to an upregulation of the immediate early gene Arc (activity-regulated cytoskeleton-associated protein) in the oval nucleus of the BNST, and a majority of these neurons expressed the 5-HT2C receptor. Finally, local infusions of a 5-HT2C receptor antagonist directly into the oval nucleus of the BNST prevented the fear memory-enhancing effects of citalopram. These findings highlight the ability of the BNST circuitry to be recruited into gating fear and anxiety-like behaviors. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Molecular interactions of agonist and inverse agonist ligands at serotonin 5-HT2C G protein-coupled receptors: computational ligand docking and molecular dynamics studies validated by experimental mutagenesis results

    Science.gov (United States)

    Córdova-Sintjago, Tania C.; Liu, Yue; Booth, Raymond G.

    2015-02-01

    To understand molecular determinants for ligand activation of the serotonin 5-HT2C G protein-coupled receptor (GPCR), a drug target for obesity and neuropsychiatric disorders, a 5-HT2C homology model was built according to an adrenergic β2 GPCR (β2AR) structure and validated using a 5-HT2B GPCR crystal structure. The models were equilibrated in a simulated phosphatidyl choline membrane for ligand docking and molecular dynamics studies. Ligands included (2S, 4R)-(-)-trans-4-(3'-bromo- and trifluoro-phenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalene-2-amine (3'-Br-PAT and 3'-CF3-PAT), a 5-HT2C agonist and inverse agonist, respectively. Distinct interactions of 3'-Br-PAT and 3'-CF3-PAT at the wild-type (WT) 5-HT2C receptor model were observed and experimental 5-HT2C receptor mutagenesis studies were undertaken to validate the modelling results. For example, the inverse agonist 3'-CF3-PAT docked deeper in the WT 5-HT2C binding pocket and altered the orientation of transmembrane helices (TM) 6 in comparison to the agonist 3'-Br-PAT, suggesting that changes in TM orientation that result from ligand binding impact function. For both PATs, mutation of 5-HT2C residues S3.36, T3.37, and F5.47 to alanine resulted in significantly decreased affinity, as predicted from modelling results. It was concluded that upon PAT binding, 5-HT2C residues T3.37 and F5.47 in TMs 3 and 5, respectively, engage in inter-helical interactions with TMs 4 and 6, respectively. The movement of TMs 5 and 6 upon agonist and inverse agonist ligand binding observed in the 5-HT2C receptor modelling studies was similar to movements reported for the activation and deactivation of the β2AR, suggesting common mechanisms among aminergic neurotransmitter GPCRs.

  12. Tokamak reactor startup power

    International Nuclear Information System (INIS)

    Weldon, D.M.; Murray, J.G.

    1983-01-01

    Tokamak startup with ohmic heating (OH)-induced voltages requires rather large voltages and power supplies. On present machines, with no radiofrequency (rf)-assist provisions, hundreds of volts have been specified for their designs. With the addition of electron cyclotron resonant heating (ECRH) assist, the design requirements have been lowered. To obtain information on the cost and complexity associated with this ECRH-assisted, OH-pulsed startup voltage for ignition-type machines, a trade-off study was completed. The Fusion Engineering Device (FED) configuration was selected as a model because information was available on the structure. The data obtained are applicable to all tokamaks of this general size and complexity, such as the Engineering Test Reactor

  13. Tokamak fusion reactor exhaust

    International Nuclear Information System (INIS)

    Harrison, M.F.A.; Harbour, P.J.; Hotston, E.S.

    1981-08-01

    This report presents a compilation of papers dealing with reactor exhaust which were produced as part of the TIGER Tokamak Installation for Generating Electricity study at Culham. The papers are entitled: (1) Exhaust impurity control and refuelling. (2) Consideration of the physical problems of a self-consistent exhaust and divertor system for a long burn Tokamak. (3) Possible bundle divertors for INTOR and TIGER. (4) Consideration of various magnetic divertor configurations for INTOR and TIGER. (5) A appraisal of divertor experiments. (6) Hybrid divertors on INTOR. (7) Refuelling and the scrape-off layer of INTOR. (8) Simple modelling of the scrape-off layer. (9) Power flow in the scrape-off layer. (10) A model of particle transport within the scrape-off plasma and divertor. (11) Controlled recirculation of exhaust gas from the divertor into the scrape-off plasma. (U.K.)

  14. Theory of tokamak plasmas

    Energy Technology Data Exchange (ETDEWEB)

    White, R B [Princeton Univ., NJ (USA). Plasma Physics Lab.

    1989-01-01

    The book covers the consequences of ideal and resistive magnetohydrodynamics, these theories being responsible for most of what is well understood regarding the physics of tokamak discharges. The focus is on the description of equilibria, the linear and nonlinear theory of large scale modes, and single particle guiding center motion, including simple neoclassical effects. modern methods of general magnetic coordinates are used, and the student is introduced to the onset of chaos in Hamiltonian systems in the discussion of destruction of magnetic surfaces. Much of the book is devoted to the description of the limitations placed on tokamak operating parameters given by ideal and resistive modes, and current ideas about how to extend and optimize these parameters. (author). refs.; figs.

  15. Axisymmetric tokamak scapeoff transport

    International Nuclear Information System (INIS)

    Singer, C.E.; Langer, W.D.

    1982-08-01

    We present the first self-consistent estimate of the magnitude of each term in a fluid treatment of plasma transport for a plasma lying in regions of open field lines in an axisymmetric tokamak. The fluid consists of a pure hydrogen plasma with sources which arise from its interaction with neutral hydrogen atoms. The analysis and results are limited to the high collisionality regime, which is optimal for a gaseous neutralizer divertor, or to a cold plasma mantle in a tokamak reactor. In this regime, both classical and neoclassical transport processes are important, and loss of particles and energy by diamagnetic flow are also significant. The prospect of extending the analysis to the lower collisionality regimes encountered in many existing experiments is discussed

  16. Density limits in Tokamaks

    International Nuclear Information System (INIS)

    Tendler, M.

    1984-06-01

    The energy loss from a tokamak plasma due to neutral hydrogen radiation and recycling is of great importance for the energy balance at the periphery. It is shown that the requirement for thermal equilibrium implies a constraint on the maximum attainable edge density. The relation to other density limits is discussed. The average plasma density is shown to be a strong function of the refuelling deposition profile. (author)

  17. Tokamak pump limiters

    International Nuclear Information System (INIS)

    Conn, R.W.

    1984-05-01

    Recent experiments with a scoop limiter without active internal pumping have been carried out in the PDX tokamak with up to 6MW of auxiliary neutral beam heating. Experiments have also been done with a rotating head pump limiter in the PLT tokamak in conjunction with RF plasma heating. Extensive experiments have been done in the ISX-B tokamak and first experiments have been completed with the ALT-I limiter in TEXTOR. The pump limiter modules in these latter two machines have internal getter pumping. Experiments in ISX-B are with ohmic and auxiliary neutral beam heating. The results in ISX-B and TEXTOR show that active density control and particle removal is achieved with pump limiters. In ISX-B, the boundary layer (or scape-off layer) plasma partially screens the core plasma from gas injection. In both ISX-B and TEXTOR, the pressure internal to the module scales linearly with plasma density but in ISX-B, with neutral beam injection, a nonlinear increase is observed at the highest densities studied. Plasma plugging is the suspected cause. Results from PDX suggest that a region may exist in which core plasma energy confinement improves using a pump limiter during neutral beam injection. Asymmetric radial profiles and an increased edge electron temperature are observed in discharges with improved confinement. The injection of small amounts of neon into ISX-B has more clearly shown an improved electron core energy confinement during neutral beam injection. While carried out with a regular limiter, this Z-mode of operation is ideal for use with pump limiters and should be a way to achieve energy confinement times similar to values for H-mode tokamak plasmas. The implication of all these results for the design of a reactor pump limiter is described

  18. Modular tokamak magnetic system

    International Nuclear Information System (INIS)

    Yang, T.F.

    1988-01-01

    This patent describes a tokamak reactor including a vacuum vessel, toroidal confining magnetic field coils disposed concentrically around the minor radius of the vacuum vessel, and poloidal confining magnetic field coils, an ohmic heating coil system comprising at least one magnetic coil disposed concentrically around a toroidal field coil, wherein the magnetic coil is wound around the toroidal field coil such that the ohmic heating coil enclosed the toroidal field coil

  19. Tokamak pump limiters

    International Nuclear Information System (INIS)

    Conn, R.W.; California Univ., Los Angeles

    1984-01-01

    Recent experiments with a scoop limiter without active internal pumping have been carried out in the PDX tokamak with up to 6 MW of auxiliary neutral beam heating. Experiments have also been performed with a rotating head pump limiter in the PLT tokamak in conjunction with RF plasma heating. Extensive experiments have been done in the ISX-B tokamak and first experiments have been completed with the ALT-I limiter in TEXTOR. The pump limiter modules in these latter two machines have internal getter pumping. Experiments in ISX-B are with ohmic and auxiliary neutral beam heating. The results in ISX-B and TEXTOR show that active density control and particle removal is achieved with pump limiters. In ISX-B, the boundary layer (or scrape-off layer) plasma partially screens the core plasma from gas injection. In both ISX-B and TEXTOR, the pressure internal to the module scales linearly with plasma density but in ISX-B, with neutral beam injection, a nonlinear increase is observed at the highest densities studied. Plasma plugging is the suspected cause. Results from PDX suggest that a regime may exist in which core plasma energy confinement improves using a pump limiter during neutral beam injection. Asymmetric radial profiles and an increased edge electron temperature are observed in discharges with improved confinement. The injection of small amounts of neon into ISX-B has more clearly shown an improved electron core energy confinement during neutral beam injection. While carried out with a regular limiter, this 'Z-mode' of operation is ideal for use with pump limiters and should be a way to achieve energy confinement times similar to values for H-mode tokamak plasmas. The implication of all these results for the design of a reactor pump limiter is described. (orig.)

  20. TPX tokamak construction management

    International Nuclear Information System (INIS)

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

    1995-01-01

    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

  1. Status of the tokamak program

    Science.gov (United States)

    Sheffield, J.

    1981-08-01

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

  2. Magnetic confinement experiment -- 1: Tokamaks

    International Nuclear Information System (INIS)

    Goldston, R.J.

    1994-01-01

    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

  3. The density limit in Tokamaks

    International Nuclear Information System (INIS)

    Alladio, F.

    1985-01-01

    A short summary of the present status of experimental observations, theoretical ideas and understanding of the density limit in tokamaks is presented. It is the result of the discussion that was held on this topic at the 4th European Tokamak Workshop in Copenhagen (December 4th to 6th, 1985). 610 refs

  4. Tokamaks - Third Edition

    International Nuclear Information System (INIS)

    Rogister, A L

    2004-01-01

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

  5. Effects of Phenolic Acids on the Growth and Production of T-2 and HT-2 Toxins by Fusarium langsethiae and F. sporotrichioides.

    Science.gov (United States)

    Ferruz, Elena; Atanasova-Pénichon, Vessela; Bonnin-Verdal, Marie-Noëlle; Marchegay, Gisèle; Pinson-Gadais, Laëtitia; Ducos, Christine; Lorán, Susana; Ariño, Agustín; Barreau, Christian; Richard-Forget, Florence

    2016-04-04

    The effect of natural phenolic acids was tested on the growth and production of T-2 and HT-2 toxins by Fusarium langsethiae and F. sporotrichioides, on Mycotoxin Synthetic medium. Plates treated with 0.5 mM of each phenolic acid (caffeic, chlorogenic, ferulic and p-coumaric) and controls without phenolic acid were incubated for 14 days at 25 °C. Fungal biomass of F. langsethiae and F. sporotrichioides was not reduced by the phenolic acids. However, biosynthesis of T-2 toxin by F. langsethiae was significantly reduced by chlorogenic (23.1%) and ferulic (26.5%) acids. Production of T-2 by F. sporotrichioides also decreased with ferulic acid by 23% (p phenolic acids had a variable effect on fungal growth and mycotoxin production, depending on the strain and the concentration and type of phenolic acid assayed.

  6. Altered 5-HT2A Receptor Binding after Recovery from Bulimia-Type Anorexia Nervosa: Relationships to Harm Avoidance and Drive for Thinness

    Science.gov (United States)

    Bailer, Ursula F; Price, Julie C; Meltzer, Carolyn C; Mathis, Chester A; Frank, Guido K; Weissfeld, Lisa; McConaha, Claire W; Henry, Shannan E; Brooks-Achenbach, Sarah; Barbarich, Nicole C; Kaye, Walter H

    2015-01-01

    Several lines of evidence suggest that a disturbance of serotonin neuronal pathways may contribute to the pathogenesis of anorexia nervosa (AN) and bulimia nervosa (BN). This study applied positron emission tomography (PET) to investigate the brain serotonin 2A (5-HT2A) receptor, which could contribute to disturbances of appetite and behavior in AN and BN. To avoid the confounding effects of malnutrition, we studied 10 women recovered from bulimia-type AN (REC AN–BN, >1 year normal weight, regular menstrual cycles, no binging, or purging) compared with 16 healthy control women (CW) using PET imaging and a specific 5-HT2A receptor antagonist, [18F]altanserin. REC AN–BN women had significantly reduced [18F]altanserin binding potential relative to CW in the left subgenual cingulate, the left parietal cortex, and the right occipital cortex. [18F]altanserin binding potential was positively related to harm avoidance and negatively related to novelty seeking in cingulate and temporal regions only in REC AN–BN subjects. In addition, REC AN–BN had negative relationships between [18F]altanserin binding potential and drive for thinness in several cortical regions. In conclusion, this study extends research suggesting that altered 5-HT neuronal system activity persists after recovery from bulimia-type AN, particularly in subgenual cingulate regions. Altered 5-HT neurotransmission after recovery also supports the possibility that this may be a trait-related disturbance that contributes to the pathophysiology of eating disorders. It is possible that subgenual cingulate findings are not specific for AN–BN, but may be related to the high incidence of lifetime major depressive disorder diagnosis in these subjects. PMID:15054474

  7. Assessment of seizure liability of Org 306039, a 5-HT2c agonist, using hippocampal brain slice and rodent EEG telemetry.

    Science.gov (United States)

    Markgraf, Carrie G; DeBoer, Erik; Zhai, Jin; Cornelius, Lara; Zhou, Ying Ying; MacSweeney, Cliona

    2014-01-01

    Evaluation of the seizure potential for a CNS-targeted pharmaceutical compound before it is administered to humans is an important part of development. The current in vitro and in vivo studies were undertaken to characterize the seizure potential of the potent and selective 5-HT2c agonist Org 306039. Rat hippocampal slices (n=5) were prepared and Org 306039 was applied over a concentration range of 0-1000μM. Male Sprague-Dawley rats, implanted with telemetry EEG recording electrodes received either vehicle (n=4) or 100mg/kg Org 306039 (n=4) by oral gavage daily for 10days. EEG was recorded continuously for 22±1h post-dose each day. Post-dose behavior observations were conducted daily for 2h. Body temperature was measured at 1 and 2h post-dose. On Day 7, blood samples were drawn for pharmacokinetic analysis of Org 306039. In hippocampal slice, Org 306039 elicited a concentration-dependent increase in population spike area and number recorded from CA1 area, indicating seizure-genic potential. In telemetered rats, Org 306039 was associated with a decrease in body weight, a decrease in body temperature and the appearance of seizure-related behaviors and pre-seizure waveforms on EEG. One rat exhibited an overt seizure. Plasma concentrations of Org 306039 were similar among the 4 rats in the Org-treated group. Small group size made it difficult to determine a PK-PD relationship. These results indicate that the in vitro and in vivo models complement each other in the characterization of the seizure potential of CNS-targeted compounds such as the 5-HT2c agonist Org 306039. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval.

    Science.gov (United States)

    Vollenweider, Franz X; Csomor, Philipp A; Knappe, Bernhard; Geyer, Mark A; Quednow, Boris B

    2007-09-01

    Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT(2A) receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT(2A) receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 microg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dose-dependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

  9. Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics.

    Science.gov (United States)

    Blasi, Giuseppe; Selvaggi, Pierluigi; Fazio, Leonardo; Antonucci, Linda Antonella; Taurisano, Paolo; Masellis, Rita; Romano, Raffaella; Mancini, Marina; Zhang, Fengyu; Caforio, Grazia; Popolizio, Teresa; Apud, Jose; Weinberger, Daniel R; Bertolino, Alessandro

    2015-06-01

    Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with second-generation antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n=63 and n=54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype-phenotype relationships.

  10. The tokamak as a neutron source

    International Nuclear Information System (INIS)

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

    1989-11-01

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

  11. Tokamak instrumentation and controls

    International Nuclear Information System (INIS)

    Becraft, W.R.; Bettis, E.S.; Houlberg, W.A.; Onega, R.J.; Stone, R.S.

    1979-02-01

    The three areas of study emphasis to date are: (1) Physics implications for controls, (2) Computer simulation, and (3) Shutdown/aborts. This document reports on the FY 78 efforts (the first year of these studies) to address these problems. Transient scenario options for the startup of a tokamak are developed, and the implications for the control system are discussed. This document also presents a hybrid computer simulation (analog and digital) of the Impurity Study Experiment (ISX-B) which is now being used for corroborative controls investigations. The simulation will be expanded to represent a TNS/ETF machine

  12. Demonstration tokamak power plant

    International Nuclear Information System (INIS)

    Abdou, M.; Baker, C.; Brooks, J.; Ehst, D.; Mattas, R.; Smith, D.L.; DeFreece, D.; Morgan, G.D.; Trachsel, C.

    1983-01-01

    A conceptual design for a tokamak demonstration power plant (DEMO) was developed. A large part of the study focused on examining the key issues and identifying the R and D needs for: (1) current drive for steady-state operation, (2) impurity control and exhaust, (3) tritium breeding blanket, and (4) reactor configuration and maintenance. Impurity control and exhaust will not be covered in this paper but is discussed in another paper in these proceedings, entitled Key Issues of FED/INTOR Impurity Control System

  13. Maximum entropy tokamak configurations

    International Nuclear Information System (INIS)

    Minardi, E.

    1989-01-01

    The new entropy concept for the collective magnetic equilibria is applied to the description of the states of a tokamak subject to ohmic and auxiliary heating. The condition for the existence of steady state plasma states with vanishing entropy production implies, on one hand, the resilience of specific current density profiles and, on the other, severe restrictions on the scaling of the confinement time with power and current. These restrictions are consistent with Goldston scaling and with the existence of a heat pinch. (author)

  14. Topology of tokamak orbits

    International Nuclear Information System (INIS)

    Rome, J.A.; Peng, Y.K.M.

    1978-09-01

    Guiding center orbits in noncircular axisymmetric tokamak plasmas are studied in the constants of motion (COM) space of (v, zeta, psi/sub m/). Here, v is the particle speed, zeta is the pitch angle with respect to the parallel equilibrium current, J/sub parallels/, and psi/sub m/ is the maximum value of the poloidal flux function (increasing from the magnetic axis) along the guiding center orbit. Two D-shaped equilibria in a flux-conserving tokamak having β's of 1.3% and 7.7% are used as examples. In this space, each confined orbit corresponds to one and only one point and different types of orbits (e.g., circulating, trapped, stagnation and pinch orbits) are represented by separate regions or surfaces in the space. It is also shown that the existence of an absolute minimum B in the higher β (7.7%) equilibrium results in a dramatically different orbit topology from that of the lower β case. The differences indicate the confinement of additional high energy (v → c, within the guiding center approximation) trapped, co- and countercirculating particles whose orbit psi/sub m/ falls within the absolute B well

  15. ITER tokamak device

    International Nuclear Information System (INIS)

    Doggett, J.; Salpietro, E.; Shatalov, G.

    1991-01-01

    The results of the Conceptual Design Activities for the International Thermonuclear Experimental Reactor (ITER) are summarized. These activities, carried out between April 1988 and December 1990, produced a consistent set of technical characteristics and preliminary plans for co-ordinated research and development support of ITER; and a conceptual design, a description of design requirements and a preliminary construction schedule and cost estimate. After a description of the design basis, an overview is given of the tokamak device, its auxiliary systems, facility and maintenance. The interrelation and integration of the various subsystems that form the ITER tokamak concept are discussed. The 16 ITER equatorial port allocations, used for nuclear testing, diagnostics, fuelling, maintenance, and heating and current drive, are given, as well as a layout of the reactor building. Finally, brief descriptions are given of the major ITER sub-systems, i.e., (i) magnet systems (toroidal and poloidal field coils and cryogenic systems), (ii) containment structures (vacuum and cryostat vessels, machine gravity supports, attaching locks, passive loops and active coils), (iii) first wall, (iv) divertor plate (design and materials, performance and lifetime, a.o.), (v) blanket/shield system, (vi) maintenance equipment, (vii) current drive and heating, (viii) fuel cycle system, and (ix) diagnostics. 11 refs, figs and tabs

  16. Dust Measurements in Tokamaks

    International Nuclear Information System (INIS)

    Rudakov, D; Yu, J; Boedo, J; Hollmann, E; Krasheninnikov, S; Moyer, R; Muller, S; Yu, A; Rosenberg, M; Smirnov, R; West, W; Boivin, R; Bray, B; Brooks, N; Hyatt, A; Wong, C; Fenstermacher, M; Groth, M; Lasnier, C; McLean, A; Stangeby, P; Ratynskaia, S; Roquemore, A; Skinner, C; Solomon, W M

    2008-01-01

    Dust production and accumulation impose safety and operational concerns for ITER. Diagnostics to monitor dust levels in the plasma as well as in-vessel dust inventory are currently being tested in a few tokamaks. Dust accumulation in ITER is likely to occur in hidden areas, e.g. between tiles and under divertor baffles. A novel electrostatic dust detector for monitoring dust in these regions has been developed and tested at PPPL. In DIII-D tokamak dust diagnostics include Mie scattering from Nd:YAG lasers, visible imaging, and spectroscopy. Laser scattering resolves size of particles between 0.16-1.6 (micro)m in diameter; the total dust content in the edge plasmas and trends in the dust production rates within this size range have been established. Individual dust particles are observed by visible imaging using fast-framing cameras, detecting dust particles of a few microns in diameter and larger. Dust velocities and trajectories can be determined in 2D with a single camera or 3D using multiple cameras, but determination of particle size is problematic. In order to calibrate diagnostics and benchmark dust dynamics modeling, pre-characterized carbon dust has been injected into the lower divertor of DIII-D. Injected dust is seen by cameras, and spectroscopic diagnostics observe an increase of carbon atomic, C2 dimer, and thermal continuum emissions from the injected dust. The latter observation can be used in the design of novel dust survey diagnostics

  17. Axisymmetric control in tokamaks

    International Nuclear Information System (INIS)

    Humphreys, D.A.

    1991-02-01

    Vertically elongated tokamak plasmas are intrinsically susceptible to vertical axisymmetric instabilities as a result of the quadrupole field which must be applied to produce the elongation. The present work analyzes the axisymmetric control necessary to stabilize elongated equilibria, with special application to the Alcator C-MOD tokamak. A rigid current-conserving filamentary plasma model is applied to Alcator C-MOD stability analysis, and limitations of the model are addressed. A more physically accurate nonrigid plasma model is developed using a perturbed equilibrium approach to estimate linearized plasma response to conductor current variations. This model includes novel flux conservation and vacuum vessel stabilization effects. It is found that the nonrigid model predicts significantly higher growth rates than predicted by the rigid model applied to the same equilibria. The nonrigid model is then applied to active control system design. Multivariable pole placement techniques are used to determine performance optimized control laws. Formalisms are developed for implementing and improving nominal feedback laws using the C-MOD digital-analog hybrid control system architecture. A proportional-derivative output observer which does not require solution of the nonlinear Ricatti equation is developed to help accomplish this implementation. The nonrigid flux conserving perturbed equilibrium plasma model indicates that equilibria with separatrix elongation of at least κ sep = 1.85 can be stabilized robustly with the present control architecture and conductor/sensor configuration

  18. Pharmacological Modulation of 5-HT2C Receptor Activity Produces Bidirectional Changes in Locomotor Activity, Responding for a Conditioned Reinforcer, and Mesolimbic DA Release in C57BL/6 Mice.

    Science.gov (United States)

    Browne, Caleb J; Ji, Xiaodong; Higgins, Guy A; Fletcher, Paul J; Harvey-Lewis, Colin

    2017-10-01

    Converging lines of behavioral, electrophysiological, and biochemical evidence suggest that 5-HT 2C receptor signaling may bidirectionally influence reward-related behavior through an interaction with the mesolimbic dopamine (DA) system. Here we directly test this hypothesis by examining how modulating 5-HT 2C receptor activity affects DA-dependent behaviors and relate these effects to changes in nucleus accumbens (NAc) DA release. In C57BL/6 mice, locomotor activity and responding for a conditioned reinforcer (CRf), a measure of incentive motivation, were examined following treatment with three 5-HT 2C receptor ligands: the agonist CP809101 (0.25-3 mg/kg), the antagonist SB242084 (0.25-1 mg/kg), or the antagonist/inverse agonist SB206553 (1-5 mg/kg). We further tested whether doses of these compounds that changed locomotor activity and responding for a CRf (1 mg/kg CP809101, 0.5 mg/kg SB242084, or 2.5 mg/kg SB206553) also altered NAc DA release using in vivo microdialysis in anesthetized mice. CP809101 reduced locomotor activity, responding for a CRf, and NAc DA release. In contrast, both SB242084 and SB206553 enhanced locomotor activity, responding for a CRf, and NAc DA release, although higher doses of SB206553 produced opposite behavioral effects. Pretreatment with the non-selective DA receptor antagonist α-flupenthixol prevented SB242084 from enhancing responding for a CRf. Thus blocking tonic 5-HT 2C receptor signaling can release serotonergic inhibition of mesolimbic DA activity and enhance reward-related behavior. The observed bidirectional effects of 5-HT 2C receptor ligands may have important implications when considering the 5-HT 2C receptor as a therapeutic target for psychiatric disorders, particularly those presenting with motivational dysfunctions.

  19. Modelling dust transport in tokamaks

    International Nuclear Information System (INIS)

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

    2008-01-01

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

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

    International Nuclear Information System (INIS)

    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

  1. Research using small tokamaks

    International Nuclear Information System (INIS)

    1991-05-01

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

  2. Natural current profiles in tokamaks

    International Nuclear Information System (INIS)

    Biskamp, D.

    1986-01-01

    It is proposed that a certain class of equilibrium, which follow from an elementary variational principle, are the natural current profiles in tokamaks, to which actual discharge profiles tend to relax. (orig.)

  3. Alcator C-Mod Tokamak

    Data.gov (United States)

    Federal Laboratory Consortium — Alcator C-Mod at the Massachusetts Institute of Technology is operated as a DOE national user facility. Alcator C-Mod is a unique, compact tokamak facility that uses...

  4. JUST: Joint Upgraded Spherical Tokamak

    International Nuclear Information System (INIS)

    Azizov, E.A.; Dvorkin, N.Ya.; Filatov, O.G.

    1997-01-01

    The main goals, ideas and the programme of JUST, spherical tokamak (ST) for the plasma burn investigation, are presented. The place and prospects of JUST in thermonuclear investigations are discussed. (author)

  5. Preliminary Design of Alborz Tokamak

    Science.gov (United States)

    Mardani, M.; Amrollahi, R.; Saramad, S.

    2012-04-01

    The Alborz tokamak is a D-shape cross section tokamak that is under construction in Amirkabir University of Technology. The most important part of the tokamak design is the design of TF coils. In this paper a refined design of the TF coil system for the Alborz tokamak is presented. This design is based on cooper cable conductor with 5 cm width and 6 mm thickness. The TF coil system is consist of 16 rectangular shape coils, that makes the magnetic field of 0.7 T at the plasma center. The stored energy in total is 160 kJ, and the power supply used in this system is a capacitor bank with capacity of C = 1.32 mF and V max = 14 kV.

  6. New directions in tokamak reactors

    International Nuclear Information System (INIS)

    Baker, C.C.

    1985-01-01

    New directions for tokamak research are briefly mentioned. Some of the areas for new considerations are the following: reactor size, beta ratio, current drivers, blankets, impurity control, and modular designs

  7. The Tokamak IST-TOK

    International Nuclear Information System (INIS)

    Varandas, C.A.F.; Cabral, J.A.C.; Manso, M.E.

    1991-01-01

    A small tokamak is under construction at the Portuguese Technical Superior Institute. The main objective is to create a home based laboratory in which an independent scientific program might be developed. (L.C.J.A.). 14 refs, 6 figs

  8. Numerical Tokamak Project code comparison

    International Nuclear Information System (INIS)

    Waltz, R.E.; Cohen, B.I.; Beer, M.A.

    1994-01-01

    The Numerical Tokamak Project undertook a code comparison using a set of TFTR tokamak parameters. Local radial annulus codes of both gyrokinetic and gyrofluid types were compared for both slab and toroidal case limits assuming ion temperature gradient mode turbulence in a pure plasma with adiabatic electrons. The heat diffusivities were found to be in good internal agreement within ± 50% of the group average over five codes

  9. Spherical tokamak development in Brazil

    International Nuclear Information System (INIS)

    Ludwig, G.O.; Del Bosco, E.; Ferreira, J.G.; Berni, L.A.; Oliveira, R.M.; Andrade, M.C.R.; Shibata, C.S.; Ueda, M.; Barroso, J.J.; Castro, P.J.; Barbosa, L.F.W.; Patire Junior, H.; The high-power microwave sources group

    2003-01-01

    This paper describes the general characteristics of spherical tokamaks, or spherical tori, with a brief overview of work in this area already performed or in progress at several institutions worldwide. The paper presents also the steps in the development of the ETE (Experimento Tokamak Esferico) project, its research program, technical characteristics and operating conditions as of December, 2002 at the Associated Plasma Laboratory (LAP) of the National Space Research Institute (INPE) in Brazil. (author)

  10. Confinement and diffusion in tokamaks

    International Nuclear Information System (INIS)

    McWilliams, R.

    1988-01-01

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

  11. Enhancement of confinement in tokamaks

    International Nuclear Information System (INIS)

    Furth, H.P.

    1986-01-01

    The analysis begins by identifying a hypothetical model of tokamak confinement that is designed to take into account the conflict between Tsub(e)(r)-profile shapes arising from microscopic transport and J(r)-profile shapes required for gross stability. On the basis of this model, a number of hypothetical lines of advance are developed. Some TFTR experiments that may point the way to a particularly attractive type of tokamak reactor regime are discussed. (author)

  12. Spherical tokamak development in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, Gerson Otto; Bosco, Edson Del; Ferreira, Julio Guimaraes [Instituto Nacional de Pesquisas Espaciais (INPE), Sao Jose dos Campos, SP (Brazil). Lab. Associado de Plasma] (and others)

    2003-07-01

    The general characteristics of spherical tokamaks, or spherical tori, with a brief view of work in this area already performed or in progress at several institutions worldwide are described. The paper presents also the steps in the development of the ETE (Experiment Tokamak spheric) project, its research program, technical characteristics and operating conditions as of December, 2002 a the Associated Plasma Laboratory (LAP) of the National Space Research Institute (INPE) in Brazil. (author)

  13. Spherical tokamak development in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, G.O.; Del Bosco, E.; Ferreira, J.G.; Berni, L.A.; Oliveira, R.M.; Andrade, M.C.R.; Shibata, C.S.; Ueda, M.; Barroso, J.J.; Castro, P.J. [Instituto Nacional de Pesquisas Espaciais (INPE), Sao Jose dos Campos, SP (Brazil). Lab. Associado de Plasma; Barbosa, L.F.W. [Universidade do Vale do Paraiba (UNIVAP), Sao Jose dos Campos, SP (Brazil). Faculdade de Engenharia, Arquitetura e Urbanismo; Patire Junior, H. [Instituto Nacional de Pesquisas Espaciais (INPE), Sao Jose dos Campos, SP (Brazil). Div. de Mecanica Espacial e Controle; The high-power microwave sources group

    2003-12-01

    This paper describes the general characteristics of spherical tokamaks, or spherical tori, with a brief overview of work in this area already performed or in progress at several institutions worldwide. The paper presents also the steps in the development of the ETE (Experimento Tokamak Esferico) project, its research program, technical characteristics and operating conditions as of December, 2002 at the Associated Plasma Laboratory (LAP) of the National Space Research Institute (INPE) in Brazil. (author)

  14. Spherical tokamak development in Brazil

    International Nuclear Information System (INIS)

    Ludwig, Gerson Otto; Bosco, Edson Del; Ferreira, Julio Guimaraes

    2003-01-01

    The general characteristics of spherical tokamaks, or spherical tori, with a brief view of work in this area already performed or in progress at several institutions worldwide are described. The paper presents also the steps in the development of the ETE (Experiment Tokamak spheric) project, its research program, technical characteristics and operating conditions as of December, 2002 a the Associated Plasma Laboratory (LAP) of the National Space Research Institute (INPE) in Brazil. (author)

  15. High Beta Tokamak research

    International Nuclear Information System (INIS)

    Navratil, G.A.; Mauel, M.E.; Ivers, T.H.; Sankar, M.K.V.; Eisner, E.; Gates, D.; Garofalo, A.; Kombargi, R.; Maurer, D.; Nadle, D.; Xiao, Q.

    1993-01-01

    During the past 6 months, experiments have been conducted with the HBT-EP tokamak in order to (1) test and evaluate diagnostic systems, (2) establish basic machine operation, (3) document MHD behavior as a function of global discharge parameters, (4) investigate conditions leading to passive stabilization of MHD instabilities, and (5) quantify the external saddle coil current required for DC mode locking. In addition, the development and installation of new hardware systems has occurred. A prototype saddle coil was installed and tested. A five-position (n,m) = (1,2) external helical saddle coil was attached for mode-locking experiments. And, fabrication of the 32-channel UV tomography and the multipass Thomson scattering diagnostics have begun in preparation for installation later this year

  16. Anomalous transport in tokamaks

    International Nuclear Information System (INIS)

    Wootton, A.J.

    1989-01-01

    A review is presented of what is known about anomalous transport in tokamaks. It is generally thought that this anomalous transport is the result of fluctuations in various plasma parameters. In the plasma edge detailed measurements of the quantities required to directly determine the fluctuation driven fluxes are available. The total flux of particles is well explained by the measured electrostatic fluctuation driven flux. However, a satisfactory model to explain the origin of the fluctuations has not been identified. The processes responsible for determining the edge energy flux are less clear, but electrostatic convection plays an important part. In the confinement region experimental observations are presently restricted to measurements of density and potential fluctuations and their correlations. The characteristics of the measured fluctuations are discussed and compared with the predictions of various models. Comparisons between measured particle, electron heat and ion heat fluxes, and those fluxes predicted to result from the measured fluctuations, are made. Magnetic fluctuations is discussed

  17. Tokamak hybrid study

    International Nuclear Information System (INIS)

    Tenney, F.H.

    1976-09-01

    A report on one year of study of a tokamak hybrid reactor is presented. The plasma is maintained by both D and T beams. To obtain long burn times a poloidal field divertor is required. Both the single null and the double null style of divertor are considered. The blanket consists of a neutron multiplier region containing natural uranium followed by burner regions of molten salt (flibe) loaded with PuF 3 to enhance the energy multiplication. Economic analysis has been applied only recently to a variety of reactor sizes and plasma conditions. Early indications suggest that the most attractive hybrids will have large plasmas of major radius in excess of 8 meters

  18. Tokamak hybrid study

    International Nuclear Information System (INIS)

    Tenney, F.H.

    1976-01-01

    A report on one year of study of a tokamak hybrid reactor is given. The plasma is maintained by both D and T beams. To obtain long burn times a poloidal field divertor is required. Both the single null and the double null style of divertor are considered. The blanket consists of a neutron multiplier region containing natural uranium followed by burner regions of molten salt (flibe) loaded with PuF 3 to enhance the energy multiplication. Economic analysis has been applied only recently to a variety of reactor sizes and plasma conditions. Early indications suggest that the most attractive hybrids will have large plasmas of major radius in excess of 8 meters

  19. The Compact Ignition Tokamak

    International Nuclear Information System (INIS)

    Schmidt, J.

    1987-01-01

    The author discusses his lab's plan for completing the Compact Ignition Tokamak (CIT) conceptual design during calendar year 1987. Around July 1 they froze the subsystem envelopes on the device to continue with the conceptual design. They did this by formalizing a general requirements document. They have been developing the management plan and submitted a version to the DOE July 10. He describes a group of management activities. They released the vacuum vessel Request For Proposals (RFP) on August 5. An RFP to do a major part of the system engineering on the device is being developed. They intend to assemble the device outside of the test cell, then move it into the the test cell, install it there, and bring to the test cell many of the auxiliary facilities from TFTR, for example, power supplies

  20. Plasma turbulence in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Caldas, Ibere L.; Heller, M.V.A.P.; Brasilio, Z.A. [Sao Paulo Univ., SP, RJ (Brazil). Inst. de Fisica

    1997-12-31

    Full text. In this work we summarize the results from experiments on electrostatic and magnetic fluctuations in tokamak plasmas. Spectral analyses show that these fluctuations are turbulent, having a broad spectrum of wavectors and a broad spectrum of frequencies at each wavector. The electrostatic turbulence induces unexpected anomalous particle transport that deteriorates the plasma confinement. The relationship of these fluctuations to the current state of plasma theory is still unclear. Furthermore, we describe also attempts to control this plasma turbulence with external magnetic perturbations that create chaotic magnetic configurations. Accordingly, the magnetic field lines may become chaotic and then induce a Lagrangian diffusion. Moreover, to discuss nonlinear coupling and intermittency, we present results obtained by using numerical techniques as bi spectral and wavelet analyses. (author)

  1. Disruptions in Tokamaks

    International Nuclear Information System (INIS)

    Bondeson, A.

    1987-01-01

    This paper discusses major and minor disruptions in Tokamaks. A number of models and numerical simulations of disruptions based on resistive MHD are reviewed. A discussion is given of how disruptive current profiles are correlated with the experimentally known operational limits in density and current. It is argued that the q a =2 limit is connected with stabilization of the m=2/n=1 tearing mode for a approx.< 2.7 by resistive walls and mode rotation. Experimental and theoretical observations indicate that major disruptions usually occur in at least two phases, first a 'predisruption', or loss of confinement in the region 1 < q < 2, leaving the q approx.= 1 region almost unaffected, followed by a final disruption of the central part, interpreted here as a toroidal n = 1 external kink mode. (author)

  2. The ARIES tokamak reactor study

    International Nuclear Information System (INIS)

    1989-10-01

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

  3. Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine D3 and serotonin 5-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior

    DEFF Research Database (Denmark)

    Butini, Stefania; Gemma, Sandra; Campiani, Giuseppe

    2009-01-01

    with a low affinity for dopamine D(2) receptors (to minimize extrapyramidal side effects), serotonin 5-HT(2C) receptors (to reduce the risk of obesity under chronic treatment), and for hERG channels (to reduce incidence of torsade des pointes). Pharmacological and biochemical data, including specific c...

  4. Estimates of regional cerebral blood flow and 5-HT2A receptor density in impulsive, aggressive dogs with 99mTc-ECD and 123I-5-I-R91150

    International Nuclear Information System (INIS)

    Peremans, Kathelijne; Coopman, Frank; Verschooten, Francis; Bree, Henri van; Audenaert, Kurt; Heeringen, Kees van; Blanckaert, Peter; Slegers, Guido; Jacobs, Filip; Otte, Andreas; Dierckx, Rudi; Mertens, John

    2003-01-01

    Impulsive aggression in dogs has an important impact on human public health. Better insight into the pathophysiology of this phenomenon could lead to more adequate diagnosis and treatment. Indirect in vivo research on peripheral body fluids and post-mortem studies in impulsive animals and humans indicate a deficient serotonergic system in general and disturbances in the serotonin-2A (5-HT2A) receptor in particular. In this study, brain perfusion and the 5-HT2A receptors were examined in impulsive, aggressive dogs, in comparison with a group of normally behaving animals. In order to decide which dogs to include in this study, owners were asked to describe the general behaviour of the dogs, the circumstances in which aggression occurred and their conduct during aggressive acts. Finally, 19 dogs were retained for this study, showing, according to different behavioural specialists, disinhibited dominance aggression. Functional imaging studies were performed on all these dogs. Single-photon emission tomography (SPET) was used to measure regional brain perfusion using technetium-99m labelled ethyl cysteinate dimer (ECD). The 5-HT2A receptor binding properties were investigated using the selective radioligand iodine-123 labelled 5-I-R91150. A significant increase in uptake of the 5-HT2A radioligand was noted in all cortical areas. No significant alterations were found in regional cortical perfusion, indicating that the increased binding index was not a consequence of increased tracer delivery. This study supports a role for the serotonergic system in canine impulsive aggression. (orig.)

  5. Estimates of regional cerebral blood flow and 5-HT2A receptor density in impulsive, aggressive dogs with {sup 99m}Tc-ECD and {sup 123}I-5-I-R91150

    Energy Technology Data Exchange (ETDEWEB)

    Peremans, Kathelijne; Coopman, Frank; Verschooten, Francis; Bree, Henri van [Department of Medical Imaging, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke (Belgium); Audenaert, Kurt; Heeringen, Kees van [Department of Psychiatry and Medical Psychology, Faculty of Medicine, Ghent University Hospital (Belgium); Blanckaert, Peter; Slegers, Guido [Laboratory of Radiopharmacy, Faculty of Pharmaceutical Sciences, Ghent University (Belgium); Jacobs, Filip; Otte, Andreas; Dierckx, Rudi [Division of Nuclear Medicine, Ghent University Hospital (Belgium); Mertens, John [VUB-Cyclotron, Brussels (Belgium)

    2003-11-01

    Impulsive aggression in dogs has an important impact on human public health. Better insight into the pathophysiology of this phenomenon could lead to more adequate diagnosis and treatment. Indirect in vivo research on peripheral body fluids and post-mortem studies in impulsive animals and humans indicate a deficient serotonergic system in general and disturbances in the serotonin-2A (5-HT2A) receptor in particular. In this study, brain perfusion and the 5-HT2A receptors were examined in impulsive, aggressive dogs, in comparison with a group of normally behaving animals. In order to decide which dogs to include in this study, owners were asked to describe the general behaviour of the dogs, the circumstances in which aggression occurred and their conduct during aggressive acts. Finally, 19 dogs were retained for this study, showing, according to different behavioural specialists, disinhibited dominance aggression. Functional imaging studies were performed on all these dogs. Single-photon emission tomography (SPET) was used to measure regional brain perfusion using technetium-99m labelled ethyl cysteinate dimer (ECD). The 5-HT2A receptor binding properties were investigated using the selective radioligand iodine-123 labelled 5-I-R91150. A significant increase in uptake of the 5-HT2A radioligand was noted in all cortical areas. No significant alterations were found in regional cortical perfusion, indicating that the increased binding index was not a consequence of increased tracer delivery. This study supports a role for the serotonergic system in canine impulsive aggression. (orig.)

  6. Association of Polymorphisms of Serotonin Transporter (5HTTLPR) and 5-HT2C Receptor Genes with Criminal Behavior in Russian Criminal Offenders

    Science.gov (United States)

    Toshchakova, Valentina A.; Bakhtiari, Yalda; Kulikov, Alexander V.; Gusev, Sergey I.; Trofimova, Marina V.; Fedorenko, Olga Yu.; Mikhalitskaya, Ekaterina V.; Popova, Nina K.; Bokhan, Nikolay A.; Hovens, Johannes E.; Loonen, Anton J.M.; Wilffert, Bob; Ivanova, Svetlana A.

    2018-01-01

    Background Human aggression is a heterogeneous behavior with biological, psychological, and social backgrounds. As the biological mechanisms that regulate aggression are components of both reward-seeking and adversity-fleeing behavior, these phenomena are difficult to disentangle into separate neurochemical processes. Nevertheless, evidence exists linking some forms of aggression to aberrant serotonergic neurotransmission. We determined possible associations between 6 serotonergic neurotransmission-related gene variants and severe criminal offenses. Methods Male Russian prisoners who were convicted for murder (n = 117) or theft (n = 77) were genotyped for variants of the serotonin transporter (5HTTLPR), tryptophan hydroxylase, tryptophan-2,3-dioxygenase, or type 2C (5-HT2C) receptor genes and compared with general-population male controls (n = 161). Prisoners were psychologically phenotyped using the Buss-Durkee Hostility Inventory and the Beck Depression Inventory. Results No differences were found between murderers and thieves either concerning genotypes or concerning psychological measures. Comparison of polymorphism distribution between groups of prisoners and controls revealed highly significant associations of 5HTTLPR and 5-HTR2C (rs6318) gene polymorphisms with being convicted for criminal behavior. Conclusions The lack of biological differences between the 2 groups of prisoners indicates that the studied 5HT-related genes do not differentiate between the types of crimes committed. PMID:29621775

  7. 123I-5-I-R91150, a new single-photon emission tomography ligand for 5-HT2A receptors: influence of age and gender in healthy subjects

    International Nuclear Information System (INIS)

    Baeken, C.; D'haenen, H.; Flamen, P.; Bossuyt, A.; Mertens, J.; Terriere, D.; Chavatte, K.; Boumon, R.

    1998-01-01

    5-HT 2A receptors have been implicated in the pathophysiology of mood disorders and in the therapeutic effect of the so-called atypical antipsychotics. Recently, a new radioiodinated ligand with high affinity and selectivity for serotonin 5-HT 2A receptors, 123 iodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl-4-methyl-4-piperidinyl] 5-iodo-2-methoxybenzamide ( 123 I-5-I-R91150), has been developed and has been shown to be suitable for single-photon emission tomography (SPET) imaging. In this study the influence of age and gender on the ligand binding was investigated in normal volunteers. One hundred and fifty MBq of 123 I-5-I-R91150 was administered to 26 normal volunteers (13 females and 13 males) with an age range of 23-60 years. SPET imaging was performed with a triple-headed gamma camera. For semi-quantitative analysis, ratios of ligand binding in different regions of interest to the binding in the cerebellum were calculated. Mean ratios of 1.7 were obtained. No gender difference was demonstrated. 5-HT 2A binding was shown to decline with age. Over an age range of 40 years a reduction in ligand binding of 42%±7% was found. These results are in agreement with in vitro and positron emission tomography findings of a decline in 5-HT 2A receptor binding with age. The findings confirm the suitability of 123 I-5-I-R91150 for SPET imaging of 5-HT 2A receptors, and highlight the necessity for age-matched controls in clinical studies. (orig.)

  8. Bibliography of fusion product physics in tokamaks

    International Nuclear Information System (INIS)

    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

  9. Tokamak engineering test reactor

    International Nuclear Information System (INIS)

    Conn, R.W.; Jassby, D.L.

    1975-07-01

    The design criteria for a tokamak engineering test reactor can be met by operating in the two-component mode with reacting ion beams, together with a new blanket-shield design based on internal neutron spectrum shaping. A conceptual reactor design achieving a neutron wall loading of about 1 MW/m 2 is presented. The tokamak has a major radius of 3.05 m, the plasma cross-section is noncircular with a 2:1 elongation, and the plasma radius in the midplane is 55 cm. The total wall area is 149 m 2 . The plasma conditions are T/sub e/ approximately T/sub i/ approximately 5 keV, and ntau approximately 8 x 10 12 cm -3 s. The plasma temperature is maintained by injection of 177 MW of 200-keV neutral deuterium beams; the resulting deuterons undergo fusion reactions with the triton-target ions. The D-shaped toroidal field coils are extended out to large major radius (7.0 m), so that the blanket-shield test modules on the outer portion of the torus can be easily removed. The TF coils are superconducting, using a cryogenically stable TiNb design that permits a field at the coil of 80 kG and an axial field of 38 kG. The blanket-shield design for the inner portion of the torus nearest the machine center line utilizes a neutron spectral shifter so that the first structural wall behind the spectral shifter zone can withstand radiation damage for the reactor lifetime. The energy attenuation in this inner blanket is 8 x 10 -6 . If necessary, a tritium breeding ratio of 0.8 can be achieved using liquid lithium cooling in the []outer blanket only. The overall power consumption of the reactor is about 340 MW(e). A neutron wall loading greater than 1 MW/m 2 can be achieved by increasing the maximum magnetic field or the plasma elongation. (auth)

  10. START: the creation of a spherical tokamak

    International Nuclear Information System (INIS)

    Sykes, Alan

    1992-01-01

    The START (Small Tight Aspect Ratio Tokamak) plasma fusion experiment is now operational at AEA Fusion's Culham Laboratory. It is the world's first experiment to explore an extreme limit of the tokamak - the Spherical Tokamak - which theoretical studies predict may have substantial advantages in the search for economic fusion power. The Head of the START project, describes the concept, some of the initial experimental results and the possibility of developing a spherical tokamak power reactor. (author)

  11. Moving Divertor Plates in a Tokamak

    International Nuclear Information System (INIS)

    Zweben, S.J.; Zhang, H.

    2009-01-01

    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

  12. Fusion potential for spherical and compact tokamaks

    International Nuclear Information System (INIS)

    Sandzelius, Mikael

    2003-02-01

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

  13. Fusion potential for spherical and compact tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Sandzelius, Mikael

    2003-02-01

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

  14. Moving Divertor Plates in a Tokamak

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Tokamak Physics Experiment (TPX) design

    International Nuclear Information System (INIS)

    Schmidt, J.A.

    1995-01-01

    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

  16. Resistive instabilities in tokamaks

    International Nuclear Information System (INIS)

    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

  17. Tokamak experimental power reactor

    International Nuclear Information System (INIS)

    Stacey, W.M. Jr.; Abdou, M.A.; Brooks, J.N.

    1978-01-01

    A tokamak experimental power reactor has been designed that is capable of producing net electric power over a wide range of possible operating conditions. A net production of 81 MW of electricity is expected from the design reference conditions that assume a value of 0.07 for beta-toroidal, a maximum toroidal magnetic field of 9 T and a thermal conversion efficiency of 30%. Impurity control is achieved through the use of a low-Z first wall coating. This approach allows a burn time of 60 seconds without the incorporation of a divertor. The system is cooled by a dual pressurized water/steam system that could potentially provide thermal efficiencies as high as 39%. The first surface facing the plasma is a low-Z coated water cooled panel that is attached to a 20 cm thick blanket module. The vacuum boundary is removed a total of 22 cm from the plasma, thereby minimizing the amount of radiation damage in this vital component. Consideration is given in the design to the possible use of the EPR as a materials test reactor. It is estimated that the total system could be built for less than 550 million dollars

  18. Classical tokamak transport theory

    International Nuclear Information System (INIS)

    Nocentini, Aldo

    1982-01-01

    A qualitative treatment of the classical transport theory of a magnetically confined, toroidal, axisymmetric, two-species plasma is presented. The 'weakly collisional' ('banana' and 'plateau') and 'collision dominated' ('Pfirsch-Schlueter' and 'highly collisional') regimes, as well as the Ware effect are discussed. The method used to evaluate the diffusion coffieicnts of particles and heat in the weakly collisional regime is based on stochastic argument, that requires an analysis of the characteristic collision frequencies and lengths for particles moving in a tokamak-like magnetic field. The same method is used to evaluate the Ware effect. In the collision dominated regime on the other hand, the particle and heat fluxes across the magnetic field lines are dominated by macroscopic effects so that, although it is possible to present them as diffusion (in fact, the fluxes turn out to be proportional to the density and temperature gradients), a macroscopic treatment is more appropriate. Hence, fluid equations are used to inveatigate the collision dominated regime, to which particular attention is devoted, having been shown relatively recently that it is more complicated than the usual Pfirsch-Schlueter regime. The whole analysis presented here is qualitative, aiming to point out the relevant physical mechanisms involved in the various regimes more than to develop a rigorous mathematical derivation of the diffusion coefficients, for which appropriate references are given. (author)

  19. Tokamak experimental power reactor

    International Nuclear Information System (INIS)

    Stacey, W.M. Jr.; Abdou, M.A.; Bertoncini, P.J.

    1976-01-01

    A conceptual design has been developed for a tokamak Experimental Power Reactor to operate at net electrical power conditions with a plant capacity factor of 50 percent for 10 yr. The EPR operates in a pulsed mode at a frequency of approximately 1/min, with approximately 75 percent duty cycle, is capable of producing approximately 72 MWe and requires 42 MWe. The annual tritium consumption is 16 kg. The EPR vacuum chamber is 6.25 m in major radius and 2.4 m in minor radius, is constructed of 2 cm thick stainless steel, and has 2 cm thick detachable, beryllium-coated coolant panels mounted on the interior. A 0.28 m stainless steel blanket and a shield ranging from 0.6 to 1.0 m surround the vacuum vessel. The coolant is H 2 O. Sixteen niobium-titanium superconducting toroidal field coils provide a field of 10 T at the coil and 4.47 T at the plasma. Superconducting ohmic heating and equilibrium field coils provide 135 V-s to drive the plasma current. Plasma heating is accomplished by 12 neutral beam injectors which provide 60 MW. The energy transfer and storage system consists of a central superconducting storage ring, a homopolar energy storage unit, and a variety of inductor-convertors

  20. The role of the spherical tokamak in clarifying tokamak physics

    International Nuclear Information System (INIS)

    Morris, A.W.; Akers, R.J.; Connor, J.W.; Counsell, G.F.; Gryaznevich, M.P.; Hender, T.C.; Maddison, G.P.; Martin, T.J.; McClements, K.G.; Roach, C.M.; Robinson, D.C.; Sykes, A.; Valovic, M.; Wilson, H.R.; Fonck, R.J.; Gusev, V.; Kaye, S.M.; Majeski, R.; Peng, Y.-K.M.; Medvedev, S.; Sharapov, S.; Walsh, M.J.

    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. (author)

  1. Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB.

    Science.gov (United States)

    Ribasés, M; Ramos-Quiroga, J A; Hervás, A; Bosch, R; Bielsa, A; Gastaminza, X; Artigas, J; Rodriguez-Ben, S; Estivill, X; Casas, M; Cormand, B; Bayés, M

    2009-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in which different genetic and environmental susceptibility factors are involved. Several lines of evidence support the view that at least 30% of ADHD patients diagnosed in childhood continue to suffer the disorder during adulthood and that genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. Genetic, biochemical and pharmacological studies support the idea that the serotonin system participates in the etiology of ADHD. Based on these data, we aimed to analyze single nucleotide polymorphisms across 19 genes involved in the serotoninergic neurotransmission in a clinical sample of 451 ADHD patients (188 adults and 263 children) and 400 controls using a population-based association study. Several significant associations were found after correcting for multiple testing: (1) the DDC gene was strongly associated with both adulthood (P=0.00053; odds ratio (OR)=2.17) and childhood ADHD (P=0.0017; OR=1.90); (2) the MAOB gene was found specifically associated in the adult ADHD sample (P=0.0029; OR=1.90) and (3) the 5HT2A gene showed evidence of association only with the combined ADHD subtype both in adults (P=0.0036; OR=1.63) and children (P=0.0084; OR=1.49). Our data support the contribution of the serotoninergic system in the genetic predisposition to ADHD, identifying common childhood and adulthood ADHD susceptibility factors, associations that are specific to ADHD subtypes and one variant potentially involved in the continuity of the disorder throughout lifespan.

  2. Advanced tokamak burning plasma experiment

    International Nuclear Information System (INIS)

    Porkolab, M.; Bonoli, P.T.; Ramos, J.; Schultz, J.; Nevins, W.N.

    2001-01-01

    A new reduced size ITER-RC superconducting tokamak concept is proposed with the goals of studying burn physics either in an inductively driven standard tokamak (ST) mode of operation, or in a quasi-steady state advanced tokamak (AT) mode sustained by non-inductive means. This is achieved by reducing the radiation shield thickness protecting the superconducting magnet by 0.34 m relative to ITER and limiting the burn mode of operation to pulse lengths as allowed by the TF coil warming up to the current sharing temperature. High gain (Q≅10) burn physics studies in a reversed shear equilibrium, sustained by RF and NB current drive techniques, may be obtained. (author)

  3. Large aspect ratio tokamak study

    International Nuclear Information System (INIS)

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

    1979-01-01

    The Large Aspect Ratio Tokamak Study (LARTS) investigated the potential for producing a viable long burn tokamak reactor through enhanced volt-second capability of the ohmic heating transformer by employing high aspect ratio designs. The plasma physics, engineering, and economic implications of high aspect ratio tokamaks were accessed in the context of extended burn operation. Plasma startup and burn parameters were addressed using a one-dimensional transport code. The pulsed electrical power requirements for the poloidal field system, which have a major impact on reactor economics, were minimized by optimizing the field in the ohmic heating coil and the wave shape of the ohmic heating discharge. A high aspect ratio reference reactor was chosen and configured

  4. Plasma boundary phenomena in tokamaks

    International Nuclear Information System (INIS)

    Stangeby, P.C.

    1989-06-01

    The focus of this review is on processes occurring at the edge, and on the connection between boundary plasma - the scrape-off layer (SOL) and the radiating layer - and central plasma processes. Techniques used for edge diagnosis are reviewed and basic experimental information (n e and T e ) is summarized. Simple models of the SOL are summarized, and the most important effects of the boundary plasma - the influence on the fuel particles, impurities, and energy - on tokamak operation dealt with. Methods of manipulating and controlling edge conditions in tokamaks and the experimental data base for the edge during auxiliary heating of tokamaks are reviewed. Fluctuations and asymmetries at the edge are also covered. (9 tabs., 134 figs., 879 refs.)

  5. Computational studies of tokamak plasmas

    International Nuclear Information System (INIS)

    Takizuka, Tomonori; Tsunematsu, Toshihide; Tokuda, Shinji

    1981-02-01

    Computational studies of tokamak plasmas are extensively advanced. Many computational codes have been developed by using several kinds of models, i.e., the finite element formulation of MHD equations, the time dependent multidimensional fluid model, and the particle model with the Monte-Carlo method. These codes are applied to the analyses of the equilibrium of an axisymmetric toroidal plasma (SELENE), the time evolution of the high-beta tokamak plasma (APOLLO), the low-n MHD stability (ERATO-J) and high-n ballooning mode stability (BOREAS) in the INTOR tokamak, the nonlinear MHD stability, such as the positional instability (AEOLUS-P), resistive internal mode (AEOLUS-I) etc., and the divertor functions. (author)

  6. Blockade of serotonin 5-HT2A receptors potentiates dopamine D2 activation-induced disruption of pup retrieval on an elevated plus maze, but has no effect on D2 blockade-induced one.

    Science.gov (United States)

    Nie, Lina; Di, Tianqi; Li, Yu; Cheng, Peng; Li, Ming; Gao, Jun

    2018-06-23

    Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D 2 receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT 2A receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT 2A on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT 2A receptors on dopamine D 2 -mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole (a D 2 agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D 2 antagonist, 0.1 or 0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT 2A receptor antagonist, 1.0 mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and tested at 30, 90 and 240 min after quinpirole or haloperidol injection on postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup retrieved (an index of maternal motivation) and sequential retrieval score (an index of executive function), prolonged the pup retrieval latencies, reduced the percentage of time spent on the open arms (an index of maternal anxiety), and decreased the distance travelled on the maze in a dose-dependent and time-dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval, but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no effect on the haloperidol-induced one. These findings suggest a complex interactive effect between 5-HT 2A and D 2 receptors on one or several maternal processes (maternal motivation, anxiety and executive function), and support the idea that one molecular mechanism by which 5-HT 2A receptors mediate maternal behavior is through

  7. Summary discussion: An integrated advanced tokamak reactor

    International Nuclear Information System (INIS)

    Sauthoff, N.R.

    1994-01-01

    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

  8. STARFIRE: a commercial tokamak reactor

    International Nuclear Information System (INIS)

    1979-12-01

    The purpose of this document is to provide an interim status report on the STARFIRE project for the period of May to September 1979. The basic objective of the STARFIRE project is to develop a design concept for a commercial tokamak fusion electric power plant based on the deuterium/tritium/lithium fuel cycle. The key technical objective is to develop the best embodiment of the tokamak as a power reactor consistent with credible engineering solutions to design problems. Another key goal of the project is to give careful attention to the safety and environmental features of a commercial fusion reactor

  9. LHCD experiments on tokamak CASTOR

    International Nuclear Information System (INIS)

    Zacek, F.; Badalec, J.; Jakubka, J.; Kryska, L.; Preinhaelter, J.; Stoeckel, J.; Valovic, M.; Nanobashvili, S.; Weixelbaum, L.; Wenzel, U.; Spineanu, F.; Vlad, M.

    1990-10-01

    A short survey is given of the experimental activities at the small Prague tokamak CASTOR. They concern primarily the LH current drive using multijunction waveguide grills as launching antennae. During two last years the, efforts were focused on a study of the electrostatic and magnetic fluctuations under conditions of combined inductive/LHCD regimes and of the relation of the level of these fluctuations to the anomalous particles transport in tokamak CASTOR. Results of the study are discussed in some detail. (author). 24 figs., 51 refs

  10. The tokamak hybrid reactor

    International Nuclear Information System (INIS)

    Kelly, J.L.; Rose, R.P.

    1981-01-01

    At a time when the potential benefits of various energy options are being seriously evaluated in many countries through-out the world, it is both timely and important to evaluate the practical application of fusion reactors for their economical production of nuclear fissile fuels from fertile fuels. The fusion hybrid reactor represents a concept that could assure the availability of adequate fuel supplies for a proven nuclear technology and have the potential of being an electrical energy source as opposed to an energy consumer as are the present fuel enrichment processes. Westinghouse Fusion Power Systems Department, under Contract No. EG-77-C-02-4544 with the Department of Energy, Office of Fusion Energy, has developed a preliminary conceptual design for an early twenty-first century fusion hybrid reactor called the commercial Tokamak Hybrid Reactor (CTHR). This design was developed as a first generation commercial plant producing fissile fuel to support a significant number of client Light Water Reactor (LWR) Plants. To the depth this study has been performed, no insurmountable technical problems have been identified. The study has provided a basis for reasonable cost estimates of the hybrid plants as well as the hybrid/LWR system busbar electricity costs. This energy system can be optimized to have a net cost of busbar electricity that is equivalent to the conventional LWR plant, yet is not dependent on uranium ore prices or standard enrichment costs, since the fusion hybrid can be fueled by numerous fertile fuel resources. A nearer-term concept is also defined using a beam driven fusion driver in lieu of the longer term ignited operating mode. (orig.)

  11. Tokamak Plasmas : Mirnov coil data analysis for tokamak ADITYA

    Indian Academy of Sciences (India)

    The spatial and temporal structures of magnetic signal in the tokamak ADITYA is analysed using recently developed singular value decomposition (SVD) technique. The analysis technique is first tested with simulated data and then applied to the ADITYA Mirnov coil data to determine the structure of current peturbation as ...

  12. The Effect of Traumatic Stress on Multiple Aminergic Systems in the Basolateral Amygdala and Hypothalamus: Specific Impairment of Serotonin 5-HT2a Receptor Signaling and its Pathophysiological Role in an Animal Model of Post Traumatic Stress Disorder

    Science.gov (United States)

    2007-02-27

    discomfort, such as pain (Tanimoto et al., 2003;Bernard et al., 1992), psychological stressors (LeDoux, 2003;LeDoux, 2000), and the disturbance of plasma...Barbarich NC, Kaye WH (2004) Altered 5-HT(2A) receptor binding after recovery from bulimia -type anorexia nervosa: relationships to harm avoidance and...Serotonin alterations in anorexia and bulimia nervosa: New insights from imaging studies. Physiology & Behavior 85:73-81. Kaye WH, Frank GK, Meltzer CC

  13. Blonanserin Ameliorates Phencyclidine-Induced Visual-Recognition Memory Deficits: the Complex Mechanism of Blonanserin Action Involving D3-5-HT2A and D1-NMDA Receptors in the mPFC

    Science.gov (United States)

    Hida, Hirotake; Mouri, Akihiro; Mori, Kentaro; Matsumoto, Yurie; Seki, Takeshi; Taniguchi, Masayuki; Yamada, Kiyofumi; Iwamoto, Kunihiro; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

    2015-01-01

    Blonanserin differs from currently used serotonin 5-HT2A/dopamine-D2 receptor antagonists in that it exhibits higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT2A receptor agonist) and 7-OH-DPAT (a dopamine-D3 receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D1 receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr197 and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser897 by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser896 by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D1-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D3 and serotonin 5-HT2A receptors in the mPFC. PMID:25120077

  14. Changes in the 5-HT2A receptor system in the pre-mammillary hypothalamus of the ewe are related to regulation of LH pulsatile secretion by an endogenous circannual rhythm

    Directory of Open Access Journals (Sweden)

    Karsch Fred J

    2003-01-01

    Full Text Available Abstract Background We wanted to determine if changes in the expression of serotonin 2A receptor (5HT2A receptor gene in the premammillary hypothalamus are associated with changes in reproductive neuroendocrine status. Thus, we compared 2 groups of ovariectomized-estradiol-treated ewes that expressed high vs low LH pulsatility in two different paradigms (2 groups per paradigm: (a refractoriness (low LH secretion or not (high LH secretion to short days in pineal-intact Ile-de-France ewes (RSD and (b endogenous circannual rhythm (ECR in free-running pinealectomized Suffolk ewes in the active or inactive stage of their reproductive rhythm. Results In RSD ewes, density of 5HT2A receptor mRNA (by in situ hybridization was significantly higher in the high LH group (25.3 ± 1.4 vs 21.4 ± 1.5 grains/neuron, P 3H-Ketanserin binding (a specific radioligand of the median part of the premammillary hypothalamus tended to be higher in the high group (29.1 ± 4.0 vs 24.6 ± 4.2 fmol/mg tissu-equivalent; P A receptor mRNA and 3H-Ketanserin binding were both significantly higher in the high LH group (20.8 ± 1.6 vs 17.0 ± 1.5 grains/neuron, P Conclusions We conclude that these higher 5HT2A receptor gene expression and binding activity of 5HT2A receptor in the premammillary hypothalamus are associated with stimulation of LH pulsatility expressed before the development of refractoriness to short days and prior to the decline of reproductive neuroendocrine activity during expression of the endogenous circannual rhythm.

  15. Energy losses on tokamak startup

    International Nuclear Information System (INIS)

    Murray, J.G.; Rothe, K.E.; Bronner, G.

    1983-01-01

    During the startup of a tokamak reactor using poloidal field (PF) coils to induce plasma currents, the conducting structures carry induced currents. The associated energy losses in the circuits must be provided by the startup coils and the PF system. This paper provides quantitative and comparitive values for the energies required as a function of the thickness or resistivity of the torus shells

  16. Prospects for Tokamak Fusion Reactors

    International Nuclear Information System (INIS)

    Sheffield, J.; Galambos, J.

    1995-01-01

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

  17. Integral torque balance in tokamaks

    International Nuclear Information System (INIS)

    Pustovitov, V.D.

    2011-01-01

    The study is aimed at clarifying the balance between the sinks and sources in the problem of intrinsic plasma rotation in tokamaks reviewed recently by deGrassie (2009 Plasma Phys. Control. Fusion 51 124047). The integral torque on the toroidal plasma is calculated analytically using the most general magnetohydrodynamic (MHD) plasma model taking account of plasma anisotropy and viscosity. The contributions due to several mechanisms are separated and compared. It is shown that some of them, though, possibly, important in establishing the rotation velocity profile in the plasma, may give small input into the integral torque, but an important contribution can come from the magnetic field breaking the axial symmetry of the configuration. In tokamaks, this can be the error field, the toroidal field ripple or the magnetic perturbation created by the correction coils in the dedicated experiments. The estimates for the error-field-induced electromagnetic torque show that the amplitude of this torque is comparable to the typical values of torques introduced into the plasma by neutral beam injection. The obtained relations allow us to quantify the effect that can be produced by the existing correction coils in tokamaks on the plasma rotation, which can be used in experiments to study the origin and physics of intrinsic rotation in tokamaks. Several problems are proposed for theoretical studies and experimental tests.

  18. ECRH Studies on Tokamak Plasmas.

    Science.gov (United States)

    1980-10-10

    r.I*cru.Dtrtibution uUnliited 300 Unicorn Pork Drive Woburn, Massachusetts 04801 ECRH STUDIES ON TOKAMAK PLASMAS JAYCOR Project No. 6183 Final Report...up techniques now in use or being suggested, include growing the plasma from a small minor radius or applying a negative voltage spike immediately

  19. Tokamak and RFP ignition requirements

    International Nuclear Information System (INIS)

    Werley, K.A.

    1991-01-01

    A plasma model is applied to calculate numerically transport- confinement (nτ 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 RAD ∼ 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 nτ 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

  20. Tokamak impurity-control techniques

    International Nuclear Information System (INIS)

    Schmidt, J.A.

    1980-01-01

    A brief review is given of the impurity-control functions in tokamaks, their relative merits and disadvantages and some prominent edge-interaction-control techniques, and there is a discussion of a new proposal, the particle scraper, and its potential advantages. (author)

  1. An enhanced tokamak startup model

    Science.gov (United States)

    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.

  2. Multimegawatt neutral beams for tokamaks

    International Nuclear Information System (INIS)

    Kunkel, W.B.

    1979-03-01

    Most of the large magnetic confinement experiments today and in the near future use high-power neutral-beam injectors to heat the plasma. This review briefly describes this remarkable technique and summarizes recent results as well as near term expectations. Progress has been so encouraging that it seems probable that tokamaks will achieve scientific breakeven before 1990

  3. Joint research using small tokamaks

    Czech Academy of Sciences Publication Activity Database

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

    2005-01-01

    Roč. 45, č. 10 (2005), S245-S254 ISSN 0029-5515. [Fusion Energy Conference contributions. Vilamoura, 1.11.2004-6.11.2004] Institutional research plan: CEZ:AV0Z20430508 Keywords : small tokamaks * thermonuclear fusion Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 3.418, year: 2005

  4. Study of polymorphic variants of the serotonin 2A receptor gene (5-HT2A) and its possible effects on smoking habits of a population from northeastern Brazil.

    Science.gov (United States)

    Ramos Neto, E S; Mágulas, J O; Sousa, J J S; Moura, A C M; Pinto, G R; Yoshioka, F K N; Canalle, R; Motta, F J N

    2014-10-20

    Previous studies have revealed a genetic component, including genetic polymorphisms in the serotonergic pathway, particularly in the serotonin receptor gene (5-HT2A). The aim of this study was to investigate associations of the T102C (rs6313) and A-1438G (rs6311) polymorphisms with tobacco use in a population from northeastern Brazil. We evaluated these polymorphisms in 135 nonsmokers and 135 smokers using polymerase chain reaction-restricted fragment length polymorphism. The distribution of allele and genotype frequencies and associations of polymorphisms with smoking were assessed with the chi-squared (χ(2)) test, the Fisher exact test, and odds ratio (OR) with a 95% confidence interval (CI). There were no differences in the distribution of genotype and allele frequencies between nonsmokers and smokers for A-1438G (P = 0.80) and T102C (P = 0.35). However, these polymorphisms were significantly associated with habit frequency (A/G: P = 0.02, OR = 6.87, 95%CI = 1.23-38.31, P = 0.04; A/G+G/G: P = 0.04, OR = 3.67, 95%CI = 1.06-12.75, P = 0.07), age of onset (C/C: P = 0.02, OR = 3.26, 95%CI = 1.17-9.07, P = 0.03, and nicotine dependence level (A/G: P = 0.02, OR = 3.28, 95%CI = 1.17-9.18, P = 0.04; A/G+G/G: P = 0.04, OR = 2.81, 95%CI = 1.13-6.99, P = 0.04; T/C: P = 0.03, OR = 3.12, 95%CI = 1.13-8.57, P = 0.04; T/C+C/C: P = 0.02, OR = 3.06, 95%CI = 1.22-7.70, P = 0.02). Therefore, these polymorphisms may not contribute significantly to smoking initiation, they do appear to be associated with habit maintenance.

  5. 5-HT2A receptor SPECT imaging with [123I]R91150 under P-gp inhibition with tariquidar: More is better?

    International Nuclear Information System (INIS)

    Tsartsalis, Stergios; Tournier, Benjamin B.; Huynh-Gatz, Trinh; Dumas, Noé; Ginovart, Nathalie; Moulin-Sallanon, Marcelle; Millet, Philippe

    2016-01-01

    Introduction: Pharmacological P-glycoprotein (P-gp) inhibition with tariquidar (TQD) is considered a promising strategy for the augmentation of radiotracer brain uptake. However, a region-dependent effect may compromise the robustness of quantitative studies. For this reason, we studied the effect of a TQD pretreatment on 5-HT2A imaging with [ 123 I]R91150 and compared results with those obtained in Mdr1a knock-out (KO) rats. Methods: Ex vivo autoradiography was performed in TQD (15 mg/kg) pretreated wild-type (WT-TQD), Mdr1a knock-out (KO) and untreated WT rats for Specific Binding Ratio (SBR) estimation. In vivo dynamic SPECT imaging with serial arterial blood sampling was performed in the former two groups of rats and kinetic analysis was performed with a one tissue-compartment (1TC) model and the Specific Uptake Ratio (SUR). Results were analyzed statistically using repeated measures ANOVA. Results: SBR values differed between WT-TQD, Mdr1a KO and WT rats in a region-dependent manner (p < 0.0001). In vivo brain uptake of radiotracer did not differ between groups. Similarly, kinetic analysis provided distribution volume (V T ) values that did not differ significantly between groups. SUR binding potential (BP ND ) values from both groups highly correlated with corresponding V T (r = 0.970, p < 0.0001 and r = 0.962, p < 0.0001, respectively). However, SUR measured over averaged images between 100 and 120 min, using cerebellum as reference region, demonstrated values that were, by average, 2.99 ± 0.53 times higher in the WT-TQD group, with the difference between groups being region-dependent (p < 0.001). In addition, coefficient of variation of the SUR BP ND values across brain regions was significantly higher in the WT-TQD rats (41.25% ± 9.63% versus 11.13% ± 5.59%, p < 0.0001). Conclusion: P-gp inhibition with TQD leads to region-dependent effect in the rat brain, with probably sub-optimal effect in cerebellum. This warrants attention when it is used as a

  6. Advanced statistics for tokamak transport colinearity and tokamak to tokamak variation

    International Nuclear Information System (INIS)

    Riedel, K.S.

    1989-01-01

    This paper is an expository introduction to advanced statistics and scaling laws and their application to tokamak devices. Topics of discussion are as follows: implicit assumptions in the standard analysis; advanced regression techniques; specialized tools in statistics and their applications in fusion physics; and improved datasets for transport studies

  7. Microwave Tokamak Experiment: Overview and status

    International Nuclear Information System (INIS)

    1990-05-01

    The Microwave Tokamak Experiment, now under construction at the Laboratory, will use microwave heating from a free-electron laser. The intense microwave pulses will be injected into the tokamak to realize several goals, including a demonstration of the effects of localized heat deposition within magnetically confined plasma, a better understanding of energy confinement in tokamaks, and use of the new free-electron laser technology for plasma heating. 3 figs., 3 tabs

  8. Combined confinement system applied to tokamaks

    International Nuclear Information System (INIS)

    Ohkawa, Tihiro

    1986-01-01

    From particle orbit point of view, a tokamak is a combined confinement configuration where a closed toroidal volume is surrounded by an open confinement system like a magnetic mirror. By eliminating a cold halo plasma, the energy loss from the plasma becomes convective. The H-mode in diverted tokamaks is an example. Because of the favorable scaling of the energy confinement time with temperature, the performance of the tokamak may be significantly improved by taking advantage of this effect. (author)

  9. Presheath profiles in simulated tokamak edge plasmas

    International Nuclear Information System (INIS)

    LaBombard, B.; Conn, R.W.; Hirooka, Y.; Lehmer, R.; Leung, W.K.; Nygren, R.E.; Ra, Y.; Tynan, G.

    1988-04-01

    The PISCES plasma surface interaction facility at UCLA generates plasmas with characteristics similar to those found in the edge plasmas of tokamaks. Steady state magnetized plasmas produced by this device are used to study plasma-wall interaction phenomena which are relevant to tokamak devices. We report here progress on some detailed investigations of the presheath region that extends from a wall surface into these /open quotes/simulated tokamak/close quotes/ edge plasma discharges along magnetic field lines

  10. Improvement of the tokamak concept

    Energy Technology Data Exchange (ETDEWEB)

    Laurent, L

    1994-12-31

    Improvement of the tokamak concept is highly desirable to reduce the size and capital cost of a device able to ignite to increase the plasma pressure, i.e. the power density to reduce the cost of electricity, and to increase the fraction of bootstrap current to render the tokamak compatible with continuous operation. The most important results obtained in this field are summarized, and the options are shown which are still open and explored by the various experiments. Various effects of the plasma shaping are discussed, plasma configurations with both high {beta}{sub N} and H{sub G} are explored, and the issues of stable steady state and of the plasma edge are briefly discussed. (R.P.). 65 refs., 2 tabs.

  11. Advanced commercial Tokamak optimization studies

    International Nuclear Information System (INIS)

    Whitley, R.H.; Berwald, D.H.; Gordon, J.D.

    1985-01-01

    Our recent studies have concentrated on developing optimal high beta (bean-shaped plasma) commercial tokamak configurations using TRW's Tokamak Reactor Systems Code (TRSC) with special emphasis on lower net electric power reactors that are more easily deployable. A wide range of issues were investigated in the search for the most economic configuration: fusion power, reactor size, wall load, magnet type, inboard blanket and shield thickness, plasma aspect ratio, and operational β value. The costs and configurations of both steady-state and pulsed reactors were also investigated. Optimal small and large reactor concepts were developed and compared by studying the cost of electricity from single units and from multiplexed units. Multiplexed units appear to have advantages because they share some plant equipment and have lower initial capital investment as compared to larger single units

  12. Flux driven turbulence in tokamaks

    International Nuclear Information System (INIS)

    Garbet, X.; Ghendrih, P.; Ottaviani, M.; Sarazin, Y.; Beyer, P.; Benkadda, S.; Waltz, R.E.

    1999-01-01

    This work deals with tokamak plasma turbulence in the case where fluxes are fixed and profiles are allowed to fluctuate. These systems are intermittent. In particular, radially propagating fronts, are usually observed over a broad range of time and spatial scales. The existence of these fronts provide a way to understand the fast transport events sometimes observed in tokamaks. It is also shown that the confinement scaling law can still be of the gyroBohm type in spite of these large scale transport events. Some departure from the gyroBohm prediction is observed at low flux, i.e. when the gradients are close to the instability threshold. Finally, it is found that the diffusivity is not the same for a turbulence calculated at fixed flux than at fixed temperature gradient, with the same time averaged profile. (author)

  13. Options for an ignited tokamak

    International Nuclear Information System (INIS)

    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 β/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

  14. Plasma diagnostics on large tokamaks

    International Nuclear Information System (INIS)

    Orlinskij, D.V.; Magyar, G.

    1988-01-01

    The main tasks of the large tokamaks which are under construction (T-15 and Tore Supra) and of those which have already been built (TFTR, JET, JT-60 and DIII-D) together with their design features which are relevant to plasma diagnostics are briefly discussed. The structural features and principal characteristics of the diagnostic systems being developed or already being used on these devices are also examined. The different diagnostic methods are described according to the physical quantities to be measured: electric and magnetic diagnostics, measurements of electron density, electron temperature, the ion components of the plasma, radiation loss measurements, spectroscopy of impurities, edge diagnostics and study of plasma stability. The main parameters of the various diagnostic systems used on the six large tokamaks are summarized in tables. (author). 351 refs, 44 figs, 22 tabs

  15. Starfire: a commercial tokamak reactor

    International Nuclear Information System (INIS)

    Baker, C.C.; Abdou, M.A.; DeFreece, D.A.; Trachsel, C.A.; Graumann, D.; Kokoszenski, J.

    1979-01-01

    The basic objective of the STARFIRE Project is to develop a design concept for a commercial tokamak fusion electric power plant based on the deuterium/tritium/lithium fuel cycle. The key technical objective is to develop the best embodiment of the tokamak as a power reactor consistent with credible engineering solutions to design problems. Another key goal of the project is to give careful attention to the safety and environmental features of a commercial fusion reactor. The STARFIRE Project was initiated in May 1979, with the goal of completing the design study by October 1980. The purpose of this paper is to present an overview of the major parameters and design features that have been tentatively selected for STARFIRE

  16. Comprehensive numerical modelling of tokamaks

    International Nuclear Information System (INIS)

    Cohen, R.H.; Cohen, B.I.; Dubois, P.F.

    1991-01-01

    We outline a plan for the development of a comprehensive numerical model of tokamaks. The model would consist of a suite of independent, communicating packages describing the various aspects of tokamak performance (core and edge transport coefficients and profiles, heating, fueling, magnetic configuration, etc.) as well as extensive diagnostics. These codes, which may run on different computers, would be flexibly linked by a user-friendly shell which would allow run-time specification of packages and generation of pre- and post-processing functions, including workstation-based visualization of output. One package in particular, the calculation of core transport coefficients via gyrokinetic particle simulation, will become practical on the scale required for comprehensive modelling only with the advent of teraFLOP computers. Incremental effort at LLNL would be focused on gyrokinetic simulation and development of the shell

  17. Magnetic island formation in tokamaks

    International Nuclear Information System (INIS)

    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

  18. Equilibrium Reconstruction in EAST Tokamak

    International Nuclear Information System (INIS)

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

    2009-01-01

    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. (magnetically confined plasma)

  19. Relaxed states of tokamak plasmas

    International Nuclear Information System (INIS)

    Kucinski, M.Y.; Okano, V.

    1993-01-01

    The relaxed states of tokamak plasmas are studied. It is assumed that the plasma relaxes to a quasi-steady state which is characterized by a minimum entropy production rate, compatible with a number of prescribed conditions and pressure balance. A poloidal current arises naturally due to the anisotropic resistivity. The minimum entropy production theory is applied, assuming the pressure equilibrium as fundamental constraint on the final state. (L.C.J.A.)

  20. Runaway electrons during tokamak startup

    International Nuclear Information System (INIS)

    Sharma, A.S.; Jayakumar, R.

    1988-01-01

    Runaway electrons significantly affect the plasma and impurity evolution during tokamak startup. During its rise, a runaway pulse stores magnetic flux inductively; this is then released during the decay phase of the runaway pulse. This process affects plasma formation, current initiation and current buildup. Because of their relativistic velocities the runaway electrons have higher ionization and excitation rates than the plasma electrons. This leads to a significant modification of the impurity behaviour and consequently the plasma evolution. (author). 20 refs, 8 figs

  1. Minimum scaling laws in tokamaks

    International Nuclear Information System (INIS)

    Zhang, Y.Z.; Mahajan, S.M.

    1986-10-01

    Scaling laws governing anomalous electron transport in tokamaks with ohmic and/or auxiliary heating are derived using renormalized Vlasov-Ampere equations for low frequency electromagnetic microturbulence. It is also shown that for pure auxiliary heating (or when auxiliary heating power far exceeds the ohmic power), the energy confinement time scales as tau/sub E/ ∼ P/sub inj//sup -1/3/, where P/sub inj/ is the injected power

  2. Gyrosheath near the tokamak edge

    International Nuclear Information System (INIS)

    Hazeltine, R.D.; Xiao, H.; Valanju, P.M.

    1993-03-01

    A new model for the structure of the radial electric field profile in the edge during the H-mode is proposed. Charge separation caused by the difference between electron and ion gyromotion, or more importantly in a tokamak, the banana motion (halo effect) can self-consistently produce an electric dipole moment that causes the sheared radial electric field. The calculated results based on the model are consistent with D-III D and TEXTOR experimental results

  3. Tokamak plasma boundary layer model

    International Nuclear Information System (INIS)

    Volkov, T.F.; Kirillov, V.D.

    1983-01-01

    A model has been developed for the limiter layer and for the boundary region of the plasma column in a tokamak to facilitate analytic calculations of the thickness of the limiter layers, the profiles and boundary values of the temperature and the density under various conditions, and the difference between the electron and ion temperatures. This model can also be used to analyze the recycling of neutrals, the energy and particle losses to the wall and the limiter, and other characteristics

  4. Shear Alfven waves in tokamaks

    International Nuclear Information System (INIS)

    Kieras, C.E.

    1982-12-01

    Shear Alfven waves in an axisymmetric tokamak are examined within the framework of the linearized ideal MHD equations. Properties of the shear Alfven continuous spectrum are studied both analytically and numerically. Implications of these results in regards to low frequency rf heating of toroidally confined plasmas are discussed. The structure of the spatial singularities associated with these waves is determined. A reduced set of ideal MHD equations is derived to describe these waves in a very low beta plasma

  5. Discharge cleaning for a tokamak

    International Nuclear Information System (INIS)

    Ishii, Shigeyuki

    1983-01-01

    Various methods of discharge cleaning for tokamaks are described. The material of the first walls of tokamaks is usually stainless steel, inconel, titanium and so on. Hydrogen is exclusively used as the discharge gas. Glow discharge cleaning (GDC), Taylor discharge cleaning (TDC), and electron cyclotron resonance discharge cleaning (ECR-DC) are discussed in this paper. The cleaning by GDC is made by moving a movable anode to the center of a tokamak vassel. Taylor found the good cleaning effect of induced discharge by high pressure and low power discharge. This is called TDC. When the frequency of high frequency discharge in a magnetic field is equal to that of the electron cyclotron resonance, the break down potential is lowered if the pressure is sufficiently low. The ECR-CD is made by using this effect. In TDC and ECR-DC, the electron temperature, which has a close relation to the production rate of H 0 , can be controlled by the pressure. In GDC, the operating pressure was improved by the radio frequency glow (RG) method. However, there is still the danger of arcing. In case of GDC and ECR-DC, the position of plasma can be controlled, but not in case of TDC. The TDC is accepted by most of takamak devices in the world. (Kato, T.)

  6. Magnetic confinement experiment. I: Tokamaks

    International Nuclear Information System (INIS)

    Goldston, R.J.

    1995-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  8. Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze

    Directory of Open Access Journals (Sweden)

    Takahashi R.N.

    2001-01-01

    Full Text Available The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats and low (spontaneously hypertensive rats, SHR anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.

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

    Science.gov (United States)

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

    2009-07-01

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

  10. Lorcaserin and CP-809101 reduce motor impulsivity and reinstatement of food seeking behavior in male rats: Implications for understanding the anti-obesity property of 5-HT2C receptor agonists.

    Science.gov (United States)

    Higgins, Guy A; Silenieks, Leo B; Altherr, Everett B; MacMillan, Cam; Fletcher, Paul J; Pratt, Wayne E

    2016-07-01

    The 5-HT2C receptor agonist lorcaserin (Belviq®) has been approved by the FDA for the treatment of obesity. Impulsivity is a contributory feature of some eating disorders. Experiments investigated the effect of lorcaserin and the highly selective 5-HT2C agonist CP-809101 on measures of impulsivity and on reinstatement of food-seeking behaviour, a model of dietary relapse. The effect of both drugs on 22-h deprivation-induced feeding was also examined, as was the effect of prefeeding in each impulsivity test. Lorcaserin (0.3-0.6 mg/kg SC) and CP-809101 (0.6-1 mg/kg SC) reduced premature responding in rats trained on the 5-CSRTT and improved accuracy in a Go-NoGo task by reducing false alarms. At equivalent doses, both drugs also reduced reinstatement for food-seeking behaviour. Neither drug altered impulsive choice measured in a delay-discounting task. Lorcaserin (1-3 mg/kg SC) and CP-809101 (3-6 mg/kg SC) reduced deprivation-induced feeding but only at higher doses. These results suggest that in addition to previously reported effects on satiety and reward, altered impulse control may represent a contributory factor to the anti-obesity property of 5-HT2C receptor agonists. Lorcaserin may promote weight loss by improving adherence to dietary regimens in individuals otherwise prone to relapse and may be beneficial in cases where obesity is associated with eating disorders tied to impulsive traits, such as binge eating disorder.

  11. The Combination of Marketed Antagonists of α1b-Adrenergic and 5-HT2A Receptors Inhibits Behavioral Sensitization and Preference to Alcohol in Mice: A Promising Approach for the Treatment of Alcohol Dependence.

    Directory of Open Access Journals (Sweden)

    Fabrice Trovero

    Full Text Available Alcohol-dependence is a chronic disease with a dramatic and expensive social impact. Previous studies have indicated that the blockade of two monoaminergic receptors, α1b-adrenergic and 5-HT2A, could inhibit the development of behavioral sensitization to drugs of abuse, a hallmark of drug-seeking and drug-taking behaviors in rodents. Here, in order to develop a potential therapeutic treatment of alcohol dependence in humans, we have blocked these two monoaminergic receptors by a combination of antagonists already approved by Health Agencies. We show that the association of ifenprodil (1 mg/kg and cyproheptadine (1 mg/kg (α1-adrenergic and 5-HT2 receptor antagonists marketed as Vadilex ® and Periactine ® in France, respectively blocks behavioral sensitization to amphetamine in C57Bl6 mice and to alcohol in DBA2 mice. Moreover, this combination of antagonists inhibits alcohol intake in mice habituated to alcohol (10% v/v and reverses their alcohol preference. Finally, in order to verify that the effect of ifenprodil was not due to its anti-NMDA receptors property, we have shown that a combination of prazosin (0.5 mg/kg, an α1b-adrenergic antagonist, Mini-Press ® in France and cyproheptadine (1 mg/kg could also reverse alcohol preference. Altogether these findings strongly suggest that combined prazosin and cyproheptadine could be efficient as a therapy to treat alcoholism in humans. Finally, because α1b-adrenergic and 5-HT2A receptors blockade also inhibits behavioral sensitization to psychostimulants, opioids and tobacco, it cannot be excluded that this combination will exhibit some efficacy in the treatment of addiction to other abused drugs.

  12. Role of the 5-HT2A Receptor in Self- and Other-Initiated Social Interaction in Lysergic Acid Diethylamide-Induced States: A Pharmacological fMRI Study.

    Science.gov (United States)

    Preller, Katrin H; Schilbach, Leonhard; Pokorny, Thomas; Flemming, Jan; Seifritz, Erich; Vollenweider, Franz X

    2018-04-04

    Distortions of self-experience are critical symptoms of psychiatric disorders and have detrimental effects on social interactions. In light of the immense need for improved and targeted interventions for social impairments, it is important to better understand the neurochemical substrates of social interaction abilities. We therefore investigated the pharmacological and neural correlates of self- and other-initiated social interaction. In a double-blind, randomized, counterbalanced, crossover study 24 healthy human participants (18 males and 6 females) received either (1) placebo + placebo, (2) placebo + lysergic acid diethylamide (LSD; 100 μg, p.o.), or (3) ketanserin (40 mg, p.o.) + LSD (100 μg, p.o.) on three different occasions. Participants took part in an interactive task using eye-tracking and functional magnetic resonance imaging completing trials of self- and other-initiated joint and non-joint attention. Results demonstrate first, that LSD reduced activity in brain areas important for self-processing, but also social cognition; second, that change in brain activity was linked to subjective experience; and third, that LSD decreased the efficiency of establishing joint attention. Furthermore, LSD-induced effects were blocked by the serotonin 2A receptor (5-HT 2A R) antagonist ketanserin, indicating that effects of LSD are attributable to 5-HT 2A R stimulation. The current results demonstrate that activity in areas of the "social brain" can be modulated via the 5-HT 2A R thereby pointing toward this system as a potential target for the treatment of social impairments associated with psychiatric disorders. SIGNIFICANCE STATEMENT Distortions of self-representation and, potentially related to this, dysfunctional social cognition are central hallmarks of various psychiatric disorders and critically impact disease development, progression, treatment, as well as real-world functioning. However, these deficits are insufficiently targeted by current treatment

  13. Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT2A receptors, in mice

    DEFF Research Database (Denmark)

    Fantegrossi, William E; Gray, Bradley W; Bailey, Jessica M

    2015-01-01

    RATIONALE: 2-([2-(4-cyano-2,5-dimethoxyphenyl)ethylamino]methyl)phenol (25CN-NBOH) is structurally similar to N-benzyl substituted phenethylamine hallucinogens currently emerging as drugs of abuse. 25CN-NBOH exhibits dramatic selectivity for 5-HT2A receptors in vitro, but has not been behaviorally...... an intermediate degree of generalization (55 %) for the DOI training dose, and these interoceptive effects were attenuated by M100907. Finally, 25CN-NBOH did not generalize to M100907 at any dose, but ketanserin fully substituted in these animals. CONCLUSIONS: 25CN-NBOH was behaviorally active, but less effective...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  15. Magnetic confinement by Tokamak: physical aspects

    International Nuclear Information System (INIS)

    Tachon, J.

    1980-01-01

    After describing the Tokamak configuration concept, the author provides an analysis of the principal physical aspects of this type of installation and concludes by estimating that the Tokamak concept is a 'plausible candidate' as a means of producing controlled thermonuclear fusion [fr

  16. Economic evaluation of tokamak power plants

    International Nuclear Information System (INIS)

    Reid, R.L.; Steiner, D.

    1977-01-01

    This study reports the impact of plasma operating characteristics, engineering options, and technology on the capital cost trends of tokamak power plants. Tokamak power systems are compared to other advanced energy systems and found to be economically competitive. A three-phase strategy for demonstrating commercial feasibility of fusion power, based on a common-site multiple-unit concept, is presented

  17. Simulation of a major tokamak disruption

    International Nuclear Information System (INIS)

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

    1977-08-01

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

  18. Diagnostics for the Rijnhuizen Tokamak Project

    NARCIS (Netherlands)

    Donne, A. J. H.

    1994-01-01

    The research program of the Rijnhuizen Tokamak Project is concentrated on the study of plasma transport processes. The RTP tokamak is therefore equipped with an extensive set of multichannel diagnostics, including a 19-channel FIR interferometer, a 20-channel heterodyne ECE system, an 80-channel

  19. MAST: a Mega Amp Spherical Tokamak

    International Nuclear Information System (INIS)

    Darke, A.C.; Harbar, J.R.; Hay, J.H.; Hicks, J.B.; Hill, J.W.; McKenzie, J.S.; Morris, A.W.; Nightingale, M.P.S.; Todd, T.N.; Voss, G.M.; Watkins, J.R.

    1995-01-01

    The highly successful tight aspect ratio tokamak research pioneered on the START machine at Culham, together with the attractive possibilities of the concept, suggest a larger device should be considered. The design of a Mega Amp Spherical Tokamak is described, operating at much higher currents and over longer pulses than START and compatible with strong additional heating. (orig.)

  20. Mercier criterion for high-β tokamaks

    International Nuclear Information System (INIS)

    Galvao, R.M.O.

    1984-01-01

    An expression, for the application of the Mercier criterion to numerical studies of diffuse high-β tokamaks (β approximatelly Σ,q approximatelly 1), which contains only leading order contributions in the high-β tokamak approximation is derived. (L.C.) [pt

  1. The ARIES-I tokamak reactor study

    International Nuclear Information System (INIS)

    1991-01-01

    This report contains an overview of the Aries-I tokamak reactor study. The following topics are discussed on this tokamak: Systems studies; equilibrium, stability, and transport; summary and conclusions; current drive; impurity control system; tritium systems; magnet engineering; fusion-power-core engineering; power conversion; Aries-I safety design and analysis; design layout and maintenance; and start-up and operations

  2. Engineering Design of KSTAR tokamak main structure

    International Nuclear Information System (INIS)

    Im, K.H.; Cho, S.; Her, N.I.

    2001-01-01

    The main components of the KSTAR (Korea Superconducting Tokamak Advanced Research) tokamak including vacuum vessel, plasma facing components, cryostat, thermal shield and magnet supporting structure are in the final stage of engineering design. Hundai Heavy Industries (HHI) has been involved in the engineering design of these components. The current configuration and the final engineering design results for the KSTAR main structure are presented. (author)

  3. Summary report on tokamak confinement experiments

    International Nuclear Information System (INIS)

    1982-03-01

    There are currently five major US tokamaks being operated and one being constructed under the auspices of the Division of Toroidal Confinement Systems. The currently operating tokamaks include: Alcator C at the Massachusetts Institute of Technology, Doublet III at the General Atomic Company, the Impurity Studies Experiment (ISX-B) at the Oak Ridge National Laboratory, and the Princeton Large Torus (PLT) and the Poloidal Divertor Experiment (PDX) at the Princeton Plasma Physics Laboratory. The Tokamak Fusion Test Reactor (TFTR) is under construction at Princeton and should be completed by December 1982. There is one major tokamak being funded by the Division of Applied Plasma Physics. The Texas Experimental Tokamak (TEXT) is being operated as a user facility by the University of Texas. The TEXT facility includes a complete set of standard diagnostics and a data acquisition system available to all users

  4. Cluster storage for COMPASS tokamak

    Czech Academy of Sciences Publication Activity Database

    Písačka, Jan; Hron, Martin; Janky, Filip; Pánek, Radomír

    2012-01-01

    Roč. 87, č. 12 (2012), s. 2238-2241 ISSN 0920-3796. [IAEA Technical Meeting on Control, Data Acquisition, and Remote Participation for Fusion Research/8./. San Francisco, 20.06.2011-24.06.2011] R&D Projects: GA ČR GAP205/11/2470; GA MŠk 7G10072; GA MŠk(CZ) LM2011021 Institutional research plan: CEZ:AV0Z20430508 Keywords : COMPASS * Tokamak * Codac * Cluster * GlusterFS * Storage Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 0.842, year: 2012 http://dx.doi.org/10.1016/j.fusengdes.2012.09.006

  5. Surface tearing modes in tokamaks

    International Nuclear Information System (INIS)

    Takizuka, Tomonori; Kurita, Gen-ichi; Azumi, Masafumi; Takeda, Tatsuoki

    1985-10-01

    Surface tearing modes in tokamaks are studied numerically and analytically. The eigenvalue problem is solved to obtain the growth rate and the mode structure. We investigate in detail dependences of the growth rate of the m/n = 2/1 resistive MHD modes on the safety factor at the plasma surface, current profile, wall position, and resistivity. The surface tearing mode moves the plasma surface even when the wall is close to the surface. The stability diagram for these modes is presented. (author)

  6. Major disruption process in tokamak

    International Nuclear Information System (INIS)

    Kurita, Gen-ichi; Azumi, Masafumi; Tuda, Takashi; Takizuka, Tomonori; Tsunematsu, Toshihide; Tokuda, Shinji; Itoh, Kimitaka; Takeda, Tatsuoki

    1981-11-01

    The major disruption in a cylindrical tokamak is investigated by using the multi-helicity code, and the destabilization of the 3/2 mode by the mode coupling with the 2/1 mode is confirmed. The evolution of the magnetic field topology caused by the major disruption is studied in detail. The effect of the internal disruption on the 2/1 magnetic island width is also studied. The 2/1 magnetic island is not enhanced by the flattening of the q-profile due to the internal disruption. (author)

  7. Association of the 5-HT2A receptor gene promoter polymorphism-1438G/A with anorexia nervosa and psychopathological traits in the Chinese Han population: A preliminary study.

    Science.gov (United States)

    Kang, Qing; Chen, Jue; Yu, Shunying; Yuan, Aihua; Zhang, Yanxia; Zhang, Ran; Jiang, Wenhui; Zhang, Chen; Zhang, Haiyin; Zhang, Mingdao; Xiao, Zeping

    2017-09-01

    The aim of the study was to explore the possible role of the 5-HT 2A -1438G/A polymorphism in the susceptibility to anorexia nervosa (AN) in the Chinese Han population. The -1438G/A polymorphism of 249 female AN patients, 228 matched healthy controls, and 198 trios was genotyped using SNaP shot assay. Psychopathological traits of eating-disordered behaviors in AN subjects were examined using the Chinese version of the Eating Disorder Examination Questionnaire. Neither the case-control analysis nor the transmission disequilibrium test revealed significant associations between the -1438G/A polymorphism and AN (P > .05). However, AA homozygote patients with AN had lower weight and shape concern scores of the EDE-Q6.0 than those of GA heterozygotes (P < .05). Our findings suggested that female AN patients with 5-HT 2A -1438AA genotype may be characterized by less severe eating-disordered psychopathological traits in the Chinese Han population. © 2017 John Wiley & Sons Australia, Ltd.

  8. Nuclear fusion research at Tokamak Energy Ltd

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  9. Enhancement of confinement in tokamaks

    International Nuclear Information System (INIS)

    Furth, H.P.

    1986-05-01

    A plausible interpretation of the experimental evidence is that energy confinement in tokamaks is governed by two separate considerations: (1) the need for resistive MHD kink-stability, which limits the permissible range of current profiles - and therefore normally also the range of temperature profiles; and (2) the presence of strongly anomalous microscopic energy transport near the plasma edge, which calibrates the amplitude of the global temperature profile, thus determining the energy confinement time tau/sub E/. Correspondingly, there are two main paths towards the enhancement of tokamak confinement: (1) Configurational optimization, to increase the MHD-stable energy content of the plasma core, can evidently be pursued by varying the cross-sectional shape of the plasma and/or finding stable radial profiles with central q-values substantially below unity - but crossing from ''first'' to ''second'' stability within the peak-pressure region would have the greatest ultimate potential. (2) Suppression of edge turbulence, so as to improve the heat insulation in the outer plasma shell, can be pursued by various local stabilizing techniques, such as use of a poloidal divertor. The present confinement model and initial TFTR pellet-injection results suggest that the introduction of a super-high-density region within the plasma core should be particularly valuable for enhancing ntau/subE/. In D-T operation, a centrally peaked plasma pressure profile could possibly lend itself to alpha-particle-driven entry into the second-stability regime

  10. CAT-D-T tokamaks

    International Nuclear Information System (INIS)

    Greenspan, E.; Blue, T.; Miley, G.H.

    1981-01-01

    The domains of plasma fuel cycles bounded by the D-T and Cat-D, and by the D-T and SCD modes of operation are examined. These domains, referred to as, respectively, the Cat-D-T and SCD-T modes of operation, are characterized by the number (γ) of tritons per fusion neutron available from external (to the plasma) sources. Two external tritium sources are considered - the blankets of the Cat-D-T (SCD-T) reactors and fission reactors supported by the Cat-D-T (SCD-T) driven hybrid reactors. It is found that by using 6 Li for the active material of the control elements of the fission reactors, it is possible to achieve γ values close to unity. Cat-D-T tokamaks could be designed to have smaller size, higher power density, lower magnetic field and even lower plasma temperature than Cat-D tokamaks; the difference becomes significant for γ greater than or equal to .75. The SCD-T mode of operation appears to be even more attractive. Promising applications identified for these Cat-D-T and SCD-T modes of operation include hybrid reactors, fusion synfuel factories and fusion reactors which have difficulty in providing all their tritium needs

  11. Plasma position control in TCABR Tokamak

    International Nuclear Information System (INIS)

    Galvao, R.M.O.; Kuznetsov, Yu. K.; Nascimento, I.C.; Fonseca, A.M.M.; Silva, R.P. da; Ruchko, L.F.; Tuszel, A.G.; Reis, A.P. dos; Sanada, E.K.

    1998-01-01

    The plasma control position in the TCABR tokamak is described. The TCA tokamak was transferred from the Centre de Recherches en Physique des Plasmas, Lausanne, to the Institute of Physics of University of Sao Paulo, renamed TCABR (α=0.18 m, R = 0.62 m, B = 1 T,I p = 100 kA). The control system was reconstructed using mainly components obtained from the TCA tokamak. A new method of plasma position determination is used in TCABR to improve its accuracy. A more detailed theoretical analysis of the feed forward and feedback control is performed as compared with. (author)

  12. Estimation of Zeff in Novillo Tokamak

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  13. Global gyrokinetic simulation of tokamak transport

    International Nuclear Information System (INIS)

    Furnish, G.; Horton, W.; Kishimoto, Y.; LeBrun, M.J.; Tajima, T.

    1998-10-01

    A kinetic simulation code based on the gyrokinetic ion dynamics in global general metric (including a tokamak with circular or noncircular cross-section) has been developed. This gyrokinetic simulation is capable of examining the global and semi-global driftwave structures and their associated transport in a tokamak plasma. The authors investigate the property of the ion temperature gradient (ITG) or η i (η i ≡ ∂ ell nT i /∂ ell n n i ) driven drift waves in a tokamak plasma. The emergent semi-global drift wave modes give rise to thermal transport characterized by the Bohm scaling

  14. Fast IR diodes thermometer for tokamak

    International Nuclear Information System (INIS)

    Chen Xiangbo

    2001-01-01

    A 30 channel fast IR pyrometry array has been constructed for tokamak, which has 0.5 μs time response, 10 mm diameter spatial resolution and 5 degree C temperature resolution. The temperature measuring range is from 250 degree C to 1200 degree C. The two dimensional temperature profiles of the first wall during both major and minor disruptions can be measured with an accuracy of about 1% measuring temperature, which is adequate for tokamak experiments. This gives a very useful tool for the disruption study, especially for the divertor physics and edge heat flux research on tokamak and other magnetic confinement devices

  15. Submillimeter wave propagation in tokamak plasmas

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  16. Power and particle exhaust in tokamaks

    International Nuclear Information System (INIS)

    Stambaugh, R.D.

    1998-01-01

    The status of power and particle exhaust research in tokamaks is reviewed in the light of ITER requirements. There is a sound basis for ITER's nominal design positions; important directions for further research are identified

  17. Definition of total bootstrap current in tokamaks

    International Nuclear Information System (INIS)

    Ross, D.W.

    1995-01-01

    Alternative definitions of the total bootstrap current are compared. An analogous comparison is given for the ohmic and auxiliary currents. It is argued that different definitions than those usually employed lead to simpler analyses of tokamak operating scenarios

  18. Tokamak research in the Soviet Union

    International Nuclear Information System (INIS)

    Strelkov, V.S.

    1981-01-01

    Important milestones on the way to the tokamak fusion reactor are recapitulated. Soviet tokamak research concentrated at the I.V. Kurchatov Institute in Moscow, the A.F. Ioffe Institute in Leningrad and the Physical-Technical Institute in Sukhumi successfully provides necessary scientific and technological data for reactor design. Achievments include, the successful operation of the first tokamak with superconducting windings (T-7) and the gyrotron set for microwave plasma heating in the T-10 tokamak. The following problems have intensively been studied: Various methods of additional plasma heating, heat and particle transport, and impurity control. The efficiency of electron-cyclotron resonance heating was demonstrated. In the Joule heating regime, both the heat conduction and diffusion rates are anomalously high, but the electron heat conduction rate decreases with increasing plasma density. Progress in impurity control makes it possible to obtain a plasma with effective charge approaching unity. (J.U.)

  19. Neutral beam in ALVAND IIC tokamak

    International Nuclear Information System (INIS)

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

    1992-01-01

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

  20. Submillimeter wave propagation in tokamak plasmas

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  1. Empirical scaling for present Ohmically heated tokamaks

    International Nuclear Information System (INIS)

    Daughney, C.

    1975-01-01

    Experimental results from the Adiabatic Toroidal Compressor (ATC) tokamak are used to obtain empirical scaling laws for the average electron temperature and electron energy confinement time as functions of the average electron density, the effective ion charge, and the plasma current. These scaling laws are extended to include dependence upon minor and major plasma radius and toroidal field strength through a comparison of the various tokamaks described in the literature. Electron thermal conductivity is the dominant loss process for the ATC tokamak. The parametric dependences of the observed electron thermal conductivity are not explained by present theoretical considerations. The electron temperature obtained with Ohmic heating is shown to be a function of current density - which will not be increased in the next generation of large tokamaks. However, the temperature dependence of the electron energy confinement time suggests that significant improvement in confinement time will be obtained with supplementary electron heating. (author)

  2. Research into controlled fusion in tokamaks

    International Nuclear Information System (INIS)

    Zacek, F.

    1992-01-01

    During the thirty years of tokamak research, physicists have been approaching step by step the reactor breakeven condition defined by the Lawson criterion. JET, the European Community tokamak is probably the first candidate among the world largest tokamaks to reach the ignition threshold and thus to demonstrate the physical feasibility of thermonuclear reaction. The record plasma parameters achieved in JET at H plasma modes due to powerful additional plasma heating and due to substantial reduction of plasma impurities, opened the door to the first experiment with a deuterium-tritium plasma. In the paper, the conditions and results of these tritium experiments are described in detail. The prospects of the world tokamak research and of the participation of Czechoslovak physicists are also discussed. (J.U.) 3 figs., 6 refs

  3. Robust Sliding Mode Control for Tokamaks

    Directory of Open Access Journals (Sweden)

    I. Garrido

    2012-01-01

    Full Text Available Nuclear fusion has arisen as an alternative energy to avoid carbon dioxide emissions, being the tokamak a promising nuclear fusion reactor that uses a magnetic field to confine plasma in the shape of a torus. However, different kinds of magnetohydrodynamic instabilities may affect tokamak plasma equilibrium, causing severe reduction of particle confinement and leading to plasma disruptions. In this sense, numerous efforts and resources have been devoted to seeking solutions for the different plasma control problems so as to avoid energy confinement time decrements in these devices. In particular, since the growth rate of the vertical instability increases with the internal inductance, lowering the internal inductance is a fundamental issue to address for the elongated plasmas employed within the advanced tokamaks currently under development. In this sense, this paper introduces a lumped parameter numerical model of the tokamak in order to design a novel robust sliding mode controller for the internal inductance using the transformer primary coil as actuator.

  4. Plasma equilibrium and instabilities in tokamaks

    International Nuclear Information System (INIS)

    Caldas, I.L.; Vannucci, A.

    1985-01-01

    A phenomenological introduction of some of the main theoretical and experimental features on equilibrium and instabilities in tokamaks is presented. In general only macroscopic effects are considered, being the plasma described as a fluid. (L.C.) [pt

  5. The ARIES-I tokamak reactor study

    International Nuclear Information System (INIS)

    1991-01-01

    This report discusses the following topics on the Aries-I Tokamak: Design description; systems studies and economics; reactor plasma physics; magnet engineering; fusion-power-ore engineering; and environmental and safety features

  6. Theory of incremental turbulent transport in tokamaks

    International Nuclear Information System (INIS)

    Similon, P.L.

    1991-01-01

    The goal of this research is to understand how the various aspect of turbulent transport operate in tokamaks, in the presence of low frequency fluctuations such as drift waves or trapped electron modes

  7. Numerical simulation of edge plasma in tokamak

    International Nuclear Information System (INIS)

    Chen Yiping; Qiu Lijian

    1996-02-01

    The transport process and transport property of plasma in edge layer of Tokamak are simulated by solving numerically two-dimensional and multi-fluid plasma transport equations using suitable simulation code. The simulation results can show plasma parameter distribution characteristics in the area of edge layer, especially the characteristics near the first wall and divertor target plate. The simulation results play an important role in the design of divertor and first wall of Tokamak. (2 figs)

  8. Plasma diagnostics using synchrotron radiation in tokamaks

    International Nuclear Information System (INIS)

    Fidone, I.; Giruzzi, G.; Granata, G.

    1995-09-01

    This report deal with the use of synchrotron radiation in tokamaks. The main advantage of this new method is that it enables to overcome several deficiencies, caused by cut-off, refraction, and harmonic overlap. It also makes it possible to enhance the informative contents of the familiar low harmonic scheme. The basic theory of the method is presented and illustrated by numerical applications, for plasma parameters of relevance in present and next step tokamaks. (TEC). 10 refs., 13 figs

  9. The ETE spherical Tokamak project. IAEA report

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, Gerson Otto; Del Bosco, E.; Berni, L.A.; Ferreira, J.G.; Oliveira, R.M.; Andrade, M.C.R.; Shibata, C.S.; Barroso, J.J.; Castro, P.J.; Patire Junior, H. [Instituto Nacional de Pesquisas Espaciais (INPE), Sao Jose dos Campos, SP (Brazil). Lab. Associado de Plasma]. E-mail: ludwig@plasma.inpe.br

    2002-07-01

    This paper describes the general characteristics of spherical tokamaks, or spherical tori, with a brief overview of work in this area already performed or in progress at several institutions worldwide. The paper presents also the historical development of the ETE (Spherical Tokamak Experiment) project, its research program, technical characteristics and operating conditions as of October, 2002 at the Associated Plasma Laboratory (LAP) of the National Space Research Institute (INPE) in Brazil. (author)

  10. Electric conductivity and bootstrap current in tokamak

    International Nuclear Information System (INIS)

    Mao Jianshan; Wang Maoquan

    1996-12-01

    A modified Ohm's law for the electric conductivity calculation is presented, where the modified ohmic current can be compensated by the bootstrap current. A comparison of TEXT tokamak experiment with the theories shows that the modified Ohm's law is a more close approximation to the tokamak experiments than the classical and neoclassical theories and can not lead to the absurd result of Z eff <1, and the extended neoclassical theory would be not necessary. (3 figs.)

  11. Erosion of the first wall of Tokamaks

    International Nuclear Information System (INIS)

    Guseva, M.I.; Ionova, E.S.; Martynenko, Yu.V.

    1980-01-01

    An estimate of the rate of erosion of the wall due to sputtering and blistering requires knowledge of the fluxes and energies of the particles which go from the plasma to the wall, of the sputtering coefficients S, and of the erosion coefficients S* for blistering. The overall erosion coefficient is equal to the sum of the sputtering coefficient and the erosion coefficient for blistering. Here the T-20 Tokamak is examined as an example of a large-scale Tokamak. 18 refs

  12. Advanced tokamak physics in DIII-D

    Energy Technology Data Exchange (ETDEWEB)

    Petty, C.C.; Luce, T.C.; Politzer, P.A.; Bray, B.; Burrell, K.H.; Chu, M.S.; Ferron, J.R.; Gohil, P.; Greenfield, C.M.; Hsieh, C.-L.; Hyatt, A.W.; La Haye, R.J.; Lao, L.L.; Leonard, A.W.; Lin-Liu, Y.R.; Lohr, J.; Mahdavi, M.A.; Petrie, T.W.; Pinsker, R.I.; Prater, R.; Scoville, J.T.; Staebler, G.M.; Strait, E.J.; Taylor, T.S.; West, W.P. [General Atomics, PO Box 85608, San Diego, CA (United States); Wade, M.R.; Lazarus, E.A.; Murakami, M. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Allen, S.L.; Casper, T.A.; Jayakumar, R.; Lasnier, C.J.; Makowski, M.A.; Rice, B.W.; Wolf, N.S. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Austin, M.E. [University of Texas, Austin, TX (United States); Fredrickson, E.D.; Gorelov, I.; Johnson, L.C.; Okabayashi, M.; Wong, K.-L. [Princeton Plasma Physics Laboratory, Princeton, NJ (United States); Garofalo, A.M.; Navratil, G.A. [Columbia University, New York (United States); Heidbrink, W. [University of California, Irvine, CA (United States); Kinsey, J.E. [Leheigh University, Bethlehem, PA (United States); McKee, G.R. [University of Wisconsin, Madison, WI (United States); Rettig, C.L.; Rhodes, T.L. [University of California, Los Angeles, CA (United States); Watkins, J.G. [Sandia National Laboratories, Albuquerque, NM (United States)

    2000-12-01

    Advanced tokamaks seek to achieve a high bootstrap current fraction without sacrificing fusion power density or fusion gain. Good progress has been made towards the DIII-D research goal of demonstrating a high-{beta} advanced tokamak plasma in steady state with a relaxed, fully non-inductive current profile and a bootstrap current fraction greater than 50%. The limiting factors for transport, stability, and current profile control in advanced operating modes are discussed in this paper. (author)

  13. Optimization design for SST-1 Tokamak insulators

    International Nuclear Information System (INIS)

    Zhang Yuanbin; Pan Wanjiang

    2012-01-01

    With the help of ANSYS FEA technique, high voltage and cryogenic proper- ties of the SST-1 Tokamak insulators were obtained, and the structure of the insulators was designed and modified by taking into account the simulation results. The simulation results indicate that the optimization structure has better high voltage insulating property and cryogenic mechanics property, and also can fulfill the qualification criteria of the SST-1 Tokamak insulators. (authors)

  14. Spherical tokamak without external toroidal fields

    International Nuclear Information System (INIS)

    Kaw, P.K.; Avinash, K.; Srinivasan, R.

    2001-01-01

    A spherical tokamak design without external toroidal field coils is proposed. The tokamak is surrounded by a spheromak shell carrying requisite force free currents to produce the toroidal field in the core. Such equilibria are constructed and it is indicated that these equilibria are likely to have robust ideal and resistive stability. The advantage of this scheme in terms of a reduced ohmic dissipation is pointed out. (author)

  15. Preliminary results of the TBR small tokamak

    International Nuclear Information System (INIS)

    Nascimento, I.C.; Fagundes, A.N.; Da Silva, R.P.; Galvao, R.M.O.; Del Bosco, E.; Vuolo, J.H.; Sanada, E.K.; Dellaqua, R.

    1982-01-01

    The paper gives a short description of the TBR - small Brazilian tokamak and the first results obtained for plasma formation and equilibrium. Measured breakdown curves for hydrogen are shown to be confined within analytically calculated limits and to depend strongly on stray vertical magnetic fields. Time profiles of plasma current in equilibrium are shown and compared with the predictions of a simple analytical model for tokamak discharges. Reasonable agreement is obtained taking Zsub(eff) as a free parameter. (author)

  16. Full power in the European tokamak

    International Nuclear Information System (INIS)

    Lallia, P.P.; Hugon, M.

    1987-01-01

    A new research campaign begins at Jet (Abingdon, UK). At this occasion, authors review and compare the performances of the three big Tokamaks that are currently in competition: Jet, JT60 and TFTR, insisting upon the European one. Conditions of ignition are reviewed together and energy losses are specified. Magnetic configurations used in tokamaks are shown, together with the technological responses brought these last years

  17. Facility approach to tokamak operation

    International Nuclear Information System (INIS)

    Edmonds, P.H.; Gabbard, W.A.

    1981-01-01

    In anticipation of the appearance of more advanced tokamaks and other fusion relevant experiments, program has been established at ORNL to systemically identify the requirements of an effective machine operations group. This program is presently applied to the ISX-B experiment. With its continuing development, it is expected to provide major support in the identification of potential problem areas and to assist in the generation of the necessary procedures for forthcoming devices. The present and future generations of large plasma devices will function as facilities, operated by an operations group as service to the plasma physicists and diagnosticians. The purpose of the program discussed here is to develop and to encourage an orderly transition to the facility-like style of operation

  18. Developments in tokamak transport modeling

    International Nuclear Information System (INIS)

    Houlberg, W.A.; Attenberger; Lao, L.L.

    1981-01-01

    A variety of numerical methods for solving the time-dependent fluid transport equations for tokamak plasmas is presented. Among the problems discussed are techniques for solving the sometimes very stiff parabolic equations for particle and energy flow, treating convection-dominated energy transport that leads to large cell Reynolds numbers, optimizing the flow of a code to reduce the time spent updating the particle and energy source terms, coupling the one-dimensional (1-D) flux-surface-averaged fluid transport equations to solutions of the 2-D Grad-Shafranov equation for the plasma geometry, handling extremely fast transient problems such as internal MHD disruptions and pellet injection, and processing the output to summarize the physics parameters over the potential operating regime for reactors. Emphasis is placed on computational efficiency in both computer time and storage requirements

  19. Simulation models for tokamak plasmas

    International Nuclear Information System (INIS)

    Dimits, A.M.; Cohen, B.I.

    1992-01-01

    Two developments in the nonlinear simulation of tokamak plasmas are described: (A) Simulation algorithms that use quasiballooning coordinates have been implemented in a 3D fluid code and a 3D partially linearized (Δf) particle code. In quasiballooning coordinates, one of the coordinate directions is closely aligned with that of the magnetic field, allowing both optimal use of the grid resolution for structures highly elongated along the magnetic field as well as implementation of the correct periodicity conditions with no discontinuities in the toroidal direction. (B) Progress on the implementation of a likeparticle collision operator suitable for use in partially linearized particle codes is reported. The binary collision approach is shown to be unusable for this purpose. The algorithm under development is a complete version of the test-particle plus source-field approach that was suggested and partially implemented by Xu and Rosenbluth

  20. Burn Control Mechanisms in Tokamaks

    Science.gov (United States)

    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.

  1. Tokamak plasma interaction with limiters

    International Nuclear Information System (INIS)

    Pitcher, C.S.

    1987-11-01

    The importance of plasma purity is first discussed in terms of the general requirements of controlled thermonuclear fusion. The tokamak approach to fusion and its inherent problem of plasma contamination are introduced. A main source of impurities is due to the bombardment of the limiter by energetic particles and thus the three main aspects of the plasma-limiter interaction are reviewed, boundary plasma conditions, fuelling/recycling and impurity production. The experiments, carried out on the DITE tokamak at Culham Laboratory, UK, investigated these three topics and the results are compared with predicted behaviour; new physical phenomena are presented in all three areas. Simple one-dimensional fluid equations are found to adequately describe the SOL plasma, except in regard to the pre-sheath electric field and ambipolarity; that is, the electric field adjacent to the limiter surface appears to be weak and the associated plasma flow can be non-ambipolar. Recycling of fuel particles from the limiter is observed to be near unity at all times. The break-up behaviour of recycled and gas puffed D 2 molecules is dependent on the electron temperature, as expected. Impurity production at the limiter is chemical erosion of graphite being negligible. Deposition of limiter and wall-produced impurities is found on the limiter. The spatial distributions of impurities released from the limiter are observed and are in good agreement with a sputtered atom transport code. Finally, preliminary experiments on the transport of impurity ions along field lines away from the limiter have been performed and compared with simple analytic theory. The results suggest that the pre-sheath electric field in the SOL is much weaker than the simple fluid model would predict

  2. Economic considerations of commercial tokamak options

    International Nuclear Information System (INIS)

    Dabiri, A.E.

    1986-05-01

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

  3. D-D tokamak reactor assessment

    International Nuclear Information System (INIS)

    Baxter, D.C.; Dabiri, A.E.

    1983-01-01

    A quantitative comparison of the physics and technology requirements, and the cost and safety performance of a d-d tokamak relative to a d-t tokamak has been performed. The first wall/blanket and energy recovery cycle for the d-d tokamak is simpler, and has a higher efficiency than the d-t tokamak. In most other technology areas (such as magnets, RF, vacuum, etc.) d-d requirements are more severe and the systems are more complex, expensive and may involve higher technical risk than d-t tokamak systems. Tritium technology for processing the plasma exhaust, and tritium refueling technology are required for d-d reactors, but no tritium containment around the blanket or heat transport system is needed. Cost studies show that for high plasma beta and high magnetic field the cost of electricity from d-d and d-t tokamaks is comparable. Safety analysis shows less radioactivity in a d-d reactor but larger amounts of stored energy and thus higher potential for energy release. Consequences of all postulated d-d accidents are significantly smaller than those from d-t reactor tritium releases

  4. Ocular Hypotensive Response in Nonhuman Primates of (8R)-1-[(2S)-2-Aminopropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol a Selective 5-HT2 Receptor Agonist.

    Science.gov (United States)

    May, Jesse A; Sharif, Najam A; McLaughlin, Marsha A; Chen, Hwang-Hsing; Severns, Bryon S; Kelly, Curtis R; Holt, William F; Young, Richard; Glennon, Richard A; Hellberg, Mark R; Dean, Thomas R

    2015-11-25

    Recently, it has been reported that 5-HT2 receptor agonists effectively reduce intraocular pressure (IOP) in a nonhuman primate model of glaucoma. Although 1-[(2S)-2-aminopropyl]indazol-6-ol (AL-34662) was shown to have good efficacy in this nonhuman primate model of ocular hypertension as well as a desirable physicochemical and permeability profile, subsequently identified cardiovascular side effects in multiple species precluded further clinical evaluation of this compound. Herein, we report selected structural modifications that resulted in the identification of (8R)-1-[(2S)-2-aminopropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol (13), which displayed an acceptable profile to support advancement for further preclinical evaluation as a candidate for proof-of-concept studies in humans.

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

    Science.gov (United States)

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

    2003-06-13

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

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

    Science.gov (United States)

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

    2014-02-01

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

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

    International Nuclear Information System (INIS)

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

    2014-03-01

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

  8. On the HL-1M tokamak plasma confinement time

    International Nuclear Information System (INIS)

    Qin Yunwen

    2001-01-01

    Emphasizing that the tokamak plasma confinement time is the plasma particle or thermal energy loss characteristic time, the relevant physical concept and HL-1M tokamak experimental data analyses are reviewed

  9. Analysis of tokamak plasma confinement modes using the fast

    Indian Academy of Sciences (India)

    The Fourier analysis is a satisfactory technique for detecting plasma confinement modes in tokamaks. The confinement mode of tokamak plasma was analysed using the fast Fourier transformation (FFT). For this purpose, we used the data of Mirnov coils that is one of the identifying tools in the IR-T1 tokamak, with and ...

  10. Comparative studies of stellarator and tokamak transport

    Energy Technology Data Exchange (ETDEWEB)

    Stroth, U; Burhenn, R; Geiger, J; Giannone, L.; Hartfuss, H J; Kuehner, G; Ledl, L; Simmet, E E; Walter, H [Max-Planck-Inst. fuer Plasmaphysik, IPP-Euratom Association, Garching (Germany); ECRH Team; W7-AS Team

    1997-09-01

    Transport properties in the W7-AS stellarator and in tokamaks are compared. The parameter dependences and the absolute values of the energy confinement time are similar. Indications are found that the density dependence, which is usually observed in stellarator confinement, can vanish above a critical density. The density dependence in stellarators seems to be similar to that in the linear ohmic confinement regime, which, in small tokamaks, extends to high density values, too. Because of the similarity in the gross confinement properties, transport in stellarators and tokamaks should not be dominated by the parameters which are very different in the two concepts, i.e. magnetic shear, major rational values of the rotational transform and plasma current. A difference in confinement is that there exists evidence for pinches in the particle and, possibly, energy transport channels in tokamaks whereas in stellarators no pinches have been observed, so far. In order to study the effect of plasma current and toroidal electric fields, stellarator discharges were carried out with an increasing amount of plasma current. From these experiments, no clear evidence of a connection of pinches with these parameters is found. The transient response in W7-AS plasmas can be described in terms of a non-local model. As in tokamaks, also cold pulse experiments in W7-AS indicate the importance of non-local transport. (author). 8 refs, 5 figs.

  11. Three novel tokamak plasma regimes in TFTR

    International Nuclear Information System (INIS)

    Furth, H.P.

    1985-10-01

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

  12. Edge plasma diagnostics on Tore Supra tokamak

    International Nuclear Information System (INIS)

    Fujita, Junji

    1991-01-01

    From 1988 to 1991, the international scientific research 'Diagnosis of peripheral plasma in Tore Supra tokamak' was carried out as a three-year plan receiving the support of the scientific research expense of the Ministry of Education. This is to apply the method of measuring electron density distribution by neutral lithium beam probe spectroscopy to the measurement of the electron density distribution in the peripheral plasma in Tore Supra Tokamak in France. Among many tokamaks in operation doing respective characteristics researches, the Tore Supra generates the toroidal magnetic field by using superconducting coils, and aims at the long time discharge for 30 sec. for the time being, and for 300 sec. in future. In the plasma generators for long time discharge like this, the technology of particle control is a large problem. For this purpose, a divertor was added to the Tore Supra. In order to advance the research on particle control, it is necessary to examine the behavior of plasma in the peripheral part in detail. The measurement of peripheral plasma in tokamaks, beam probe spectroscopy, the Tore Supra tokamak, the progress of the joint research, the problems in the joint research and the perspective of hereafter are reported. (K.I.)

  13. Electron thermal transport in tokamak plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Konings, J A

    1994-11-30

    The process of fusion of small nuclei thereby releasing energy, as it occurs continuously in the sun, is essential for the existence of mankind. The same process applied in a controlled way on earth would provide a clean and an abundant energy source, and be the long term solution of the energy problem. Nuclear fusion requires an extremely hot (10{sup 8} K) ionized gas, a plasma, that can only be maintained if it is kept insulated from any material wall. In the so called `tokamak` this is achieved by using magnetic fields. The termal insulation, which is essential if one wants to keep the plasma at the high `fusion` temperature, can be predicted using basic plasma therory. A comparison with experiments in tokamaks, however, showed that the electron enery losses are ten to hundred times larger than this theory predicts. This `anomalous transport` of thermal energy implies that, to reach the condition for nuclear fusion, a fusion reactor must have very large dimensions. This may put the economic feasibility of fusion power in jeopardy. Therefore, in a worldwide collaboration, physicists study tokamak plasmas in an attempt to understand and control the energy losses. From a scientific point of view, the mechanisms driving anomalous transport are one of the challenges in fudamental plasma physics. In Nieuwegein, a tokamak experiment (the Rijnhuizen Tokamak Project, RTP) is dedicated to the study of anomalous transport, in an international collaboration with other laboratories. (orig./WL).

  14. Neoclassical MHD equations for tokamaks

    International Nuclear Information System (INIS)

    Callen, J.D.; Shaing, K.C.

    1986-03-01

    The moment equation approach to neoclassical-type processes is used to derive the flows, currents and resistive MHD-like equations for studying equilibria and instabilities in axisymmetric tokamak plasmas operating in the banana-plateau collisionality regime (ν* approx. 1). The resultant ''neoclassical MHD'' equations differ from the usual reduced equations of resistive MHD primarily by the addition of the important viscous relaxation effects within a magnetic flux surface. The primary effects of the parallel (poloidal) viscous relaxation are: (1) Rapid (approx. ν/sub i/) damping of the poloidal ion flow so the residual flow is only toroidal; (2) addition of the bootstrap current contribution to Ohm's laws; and (3) an enhanced (by B 2 /B/sub theta/ 2 ) polarization drift type term and consequent enhancement of the perpendicular dielectric constant due to parallel flow inertia, which causes the equations to depend only on the poloidal magnetic field B/sub theta/. Gyroviscosity (or diamagnetic vfiscosity) effects are included to properly treat the diamagnetic flow effects. The nonlinear form of the neoclassical MHD equations is derived and shown to satisfy an energy conservation equation with dissipation arising from Joule and poloidal viscous heating, and transport due to classical and neoclassical diffusion

  15. Alfven Eigenmodes in spherical tokamaks

    International Nuclear Information System (INIS)

    Gryaznevich, Mikhail P.; Sharapov, Sergei E.; Berk, Herbert L.; Pinches, Simon D.

    2005-01-01

    Electromagnetic instabilities are often excited by fast super-Alfvenic ions produced by neutral beam injection (NBI) in plasmas of the spherical tokamaks START and MAST (toroidal magnetic confinement devices in which the minor a and major R 0 radii of the torus are comparable, R 0 /a≅1.2/1.8). These instabilities are seen as discrete weakly-damped toroidal and elliptical Alfven Eigenmodes (TAEs and EAEs) with frequencies tracing in time the Alfven scaling with the equilibrium magnetic field and plasma density, or as energetic particle modes (EPMs) whose frequencies don't start from TAE-frequency and sweep down in time faster than the equilibrium parameters change. In some discharges the beam drives Aflvenic-type modes that start from the TAE frequency and sweep in both up- and down- directions. Such electromagnetic perturbations are interpreted as 'hole-clump' long-living nonlinear fluctuations of the fast ion distribution function predicted by Berk-Breizman-Petviashvili [Phys. Lett. A238 (1998) 408]. It is found on both START and MAST that the Alfven instabilities weaken in their mode amplitude and in the number of unstable modes as the pressure of the thermal plasma increases, in agreement with increased thermal ion Landau damping and the pressure effect on core-localised TAEs. (author)

  16. The collaborative tokamak control room

    International Nuclear Information System (INIS)

    Schissel, D.P.

    2006-01-01

    Magnetic fusion experiments keep growing in size and complexity resulting in a concurrent growth in collaborations between experimental sites and laboratories worldwide. In the US, the National Fusion Collaboratory Project is developing a persistent infrastructure to enable scientific collaboration for all aspects of magnetic fusion energy research by creating a robust, user-friendly collaborative environment and deploying this to the more than 1000 US fusion scientists in 40 institutions who perform magnetic fusion research. This paper reports on one aspect of the project which is the development of the collaborative tokamak control room to enhance both collocated and remote scientific participation in experimental operations. This work includes secured computational services that can be scheduled as required, the ability to rapidly compare experimental data with simulation results, a means to easily share individual results with the group by moving application windows to a shared display, and the ability for remote scientists to be fully engaged in experimental operations through shared audio, video, and applications. The project is funded by the USDOE Office of Science, Scientific Discovery through Advanced Computing (SciDAC) Program and unites fusion and computer science researchers to directly address these challenges

  17. Tokamak rotation and charge exchange

    International Nuclear Information System (INIS)

    Hazeltine, R.D.; Rowan, W.L.; Solano, E.R.; Valanju, P.M.

    1991-01-01

    In the absence of momentum input, tokamak toroidal rotation rates are typically small - no larger in particular than poloidal rotation - even when the radial electric field is strong, as near the plasma edge. This circumstance, contradicting conventional neoclassical theory, is commonly attributed to the rotation damping effect of charge exchange, although a detailed comparison between charge-exchange damping theory and experiment is apparently unavailable. Such a comparison is attempted here in the context of recent TEXT experiments, which compare rotation rates, both poloidal and toroidal, in helium and hydrogen discharges. The helium discharges provide useful data because they are nearly free of ion-neutral charge exchange; they have been found to rotate toroidally in reasonable agreement with neoclassical predictions. The hydrogen experiments show much smaller toroidal motion as usual. The theoretical calculation uses the full charge-exchange operator and assumes plateau collisionality, roughly consistent with the experimental conditions. The authors calculate the ion flow as a function of v cx /v c , where v cx is the charge exchange rate and v c the Coulomb collision frequency. The results are in reasonable accord with the observations. 1 ref

  18. Progress of the ECH·ECCD experiments. Research progress of the ECH·ECCD experiments in tokamaks and spherical tokamaks

    International Nuclear Information System (INIS)

    Isayama, Akihiko; Tanaka, Hitoshi

    2009-01-01

    Recent progress in the ECH·ECCD study in tokamak and spherical tokamak devices is described. As for the tokamak study, results on the control of neoclassical tearing modes and sawtooth oscillations, the current profile, the internal transport barrier, the plasma start-up and the discharge cleaning are given. As for the spherical tokamak study, the plasma start-up by ECH·ECCD and the electron-Bernstein-wave heating and the current drive are described. (T.I.)

  19. Modelling of Ohmic discharges in ADITYA tokamak using the Tokamak Simulation Code

    International Nuclear Information System (INIS)

    Bandyopadhyay, I; Ahmed, S M; Atrey, P K; Bhatt, S B; Bhattacharya, R; Chaudhury, M B; Deshpande, S P; Gupta, C N; Jha, R; Joisa, Y Shankar; Kumar, Vinay; Manchanda, R; Raju, D; Rao, C V S; Vasu, P

    2004-01-01

    Several Ohmic discharges of the ADITYA tokamak are simulated using the Tokamak Simulation Code (TSC), similar to that done earlier for the TFTR tokamak. Unlike TFTR, the dominant radiation process in ADITYA is through impurity line radiation. TSC can follow the experimental plasma current and position to very good accuracy. The thermal transport model of TSC including impurity line radiation gives a good match of the simulated results with experimental data for the Ohmic flux consumption, electron temperature and Z eff . Even the simulated magnetic probe signals are in reasonably good agreement with the experimental values

  20. Modelling of Ohmic discharges in ADITYA tokamak using the Tokamak Simulation Code

    Energy Technology Data Exchange (ETDEWEB)

    Bandyopadhyay, I; Ahmed, S M; Atrey, P K; Bhatt, S B; Bhattacharya, R; Chaudhury, M B; Deshpande, S P; Gupta, C N; Jha, R; Joisa, Y Shankar; Kumar, Vinay; Manchanda, R; Raju, D; Rao, C V S; Vasu, P [Institute for Plasma Research, Bhat, Gandhinagar 382428 (India)

    2004-09-01

    Several Ohmic discharges of the ADITYA tokamak are simulated using the Tokamak Simulation Code (TSC), similar to that done earlier for the TFTR tokamak. Unlike TFTR, the dominant radiation process in ADITYA is through impurity line radiation. TSC can follow the experimental plasma current and position to very good accuracy. The thermal transport model of TSC including impurity line radiation gives a good match of the simulated results with experimental data for the Ohmic flux consumption, electron temperature and Z{sub eff}. Even the simulated magnetic probe signals are in reasonably good agreement with the experimental values.

  1. Heat load material studies: Simulated tokamak disruptions

    International Nuclear Information System (INIS)

    Gahl, J.M.; McDonald, J.M.; Zakharov, A.; Tserevitinov, S.; Barabash, V.; Guseva, M.

    1991-01-01

    It is clear that an improved understanding of the effects of tokamak disruptions on plasma facing component materials is needed for the ITER program. very large energy fluxes are predicted to be deposited in ITER and could be very damaging to the machine. During 1991, Sandia National Laboratories and the University of New Mexico conducted cooperative tokamak disruption simulation experiments at several Soviet facilities. These facilities were located at the Efremov Institute in Leningrad, the Kurchatov Atomic Energy Institute (Troisk and Moscow) and the Institute for Physical Chemistry of the Soviet Adademy of Sciences in Moscow. Erosion of graphite from plasma stream impact is seen to be much less than that observed with laser or electron beams with similar energy fluxes. This, along with other data obtained, seem to suggest that the ''vapor shielding'' effect is a very important phenomenon in the study of graphite erosion during tokamak disruption

  2. Effect of impurity radiation on tokamak equilibrium

    International Nuclear Information System (INIS)

    Rebut, P.H.; Green, B.J.

    1977-01-01

    The energy loss from a tokamak plasma due to the radiation from impurities is of great importance in the overall energy balance. Taking the temperature dependence of this loss for two impurities characteristic of those present in existing tokamak plasmas, the condition for radial power balance is derived. For the impurities considered (oxygen and iron) it is found that the radiation losses are concentrated in a thin outer layer of the plasma and the equilibrium condition places an upper limit on the plasma paraticle number density in this region. This limiting density scales with mean current density in the same manner as is experimentally observed for the peak number density of tokamak plasmas. The stability of such equilibria is also discussed. (author)

  3. Spherical tokamak power plant design issues

    International Nuclear Information System (INIS)

    Hender, T.C.; Bond, A.; Edwards, J.; Karditsas, P.J.; McClements, K.G.; Mustoe, J.; Sherwood, D.V.; Voss, G.M.; Wilson, H.R.

    2000-01-01

    The very high β potential of the spherical tokamak has been demonstrated in the START experiment. Systems code studies show the cost of electricity from spherical tokamak power plants, operating at high β in second ballooning mode stable regime, is comparable with fossil fuels and fission. Outline engineering designs are presented based on two concepts for the central rod of the toroidal field (TF) circuit - a room temperature water cooled copper rod or a helium cooled cryogenic aluminium rod. For the copper rod case the TF return limbs are supported by the vacuum vessel, while for the aluminium rod the TF coils form an independent structure. In both cases thermohydraulic and stress calculations indicate the viability of the design. Two-dimensional neutronics calculations show the feasibility of tritium self-sufficiency without an inboard blanket. The spherical tokamak has unique maintenance possibilities based on lowering major component structures into a hot cell beneath the device and these are discussed

  4. Time - resolved thermography at Tokamak T-10

    International Nuclear Information System (INIS)

    Grunow, C.; Guenther, K.; Lingertat, J.; Chicherov, V.M.; Evstigneev, S.A.; Zvonkov, S.N.

    1987-01-01

    Thermographic experiments were performed at T-10 tokamak to investigate the thermic coupling of plasma and the limiter. The limiter is an internal equipment of the vacuum vessel of tokamak-type fusion devices and the interaction of plasma with limiter results a high thermal load of limiter for short time. In according to improve the limiter design the temperature distribution on the limiter surface was measured by a time-resolved thermographic method. Typical isotherms and temperature increment curves are presented. This measurement can be used as a systematic plasma diagnostic method because the limiter is installed in the tokamak whereas special additional probes often disturb the plasma discharge. (D.Gy.) 3 refs.; 7 figs

  5. Magnet design considerations for Tokamak fusion reactors

    International Nuclear Information System (INIS)

    Purcell, J.R.; Chen, W.; Thomas, R.

    1976-01-01

    Design problems for superconducting ohmic heating and toroidal field coils for large Tokamak fusion reactors are discussed. The necessity for making these coils superconducting is explained, together with the functions of these coils in a Tokamak reactor. Major problem areas include materials related aspects and mechanical design and cryogenic considerations. Projections and comparisons are made based on existing superconducting magnet technology. The mechanical design of large-scale coils, which can contain the severe electromagnetic loading and stress generated in the winding, are emphasized. Additional major tasks include the development of high current conductors for pulsed applications to be used in fabricating the ohmic heating coils. It is important to note, however, that no insurmountable technical barriers are expected in the course of developing superconducting coils for Tokamak fusion reactors. (Auth.)

  6. Ripple induced trapped particle loss in tokamaks

    International Nuclear Information System (INIS)

    White, R.B.

    1996-05-01

    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 axisymmetric orbit loss, ripple trapping, convective banana flow, and stochastic ripple loss, which gives accurate ripple loss predictions for representative Tokamak Fusion Test Reactor and International Thermonuclear Experimental Reactor equilibria. The algorithm is extended to include the effects of collisions and drag, allowing rapid estimation of alpha particle loss in tokamaks

  7. Activation analysis of the compact ignition tokamak

    International Nuclear Information System (INIS)

    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

  8. Helicity content and tokamak applications of helicity

    International Nuclear Information System (INIS)

    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

  9. Proposed tokamak poloidal field system development program

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, J.D.; Vogel, H.F.; Warren, R.W.; Weldon, D.M.

    1977-05-01

    A program is proposed to develop poloidal field components for TNS and EPR size tokamak devices and to test these components in realistic circuits. Emphasis is placed upon the development of the most difficult component, the superconducting ohmic-heating coil. Switches must also be developed for testing the coils, and this switching technology is to be extended to meet the requirements for the large scale tokamaks. Test facilities are discussed; power supplies, including a homopolar to drive the coils, are considered; and poloidal field systems studies are proposed.

  10. Tokamak Engineering Technology Facility scoping study

    Energy Technology Data Exchange (ETDEWEB)

    Stacey, W.M. Jr.; Abdou, M.A.; Bolta, C.C.

    1976-03-01

    A scoping study for a Tokamak Engineering Technology Facility (TETF) is presented. The TETF is a tokamak with R = 3 m and I/sub p/ = 1.4 MA based on the counterstreaming-ion torus mode of operation. The primary purpose of TETF is to demonstrate fusion technologies for the Experimental Power Reactor (EPR), but it will also serve as an engineering and radiation test facility. TETF has several technological systems (e.g., superconducting toroidal-field coil, tritium fuel cycle, impurity control, first wall) that are prototypical of EPR.

  11. Ballooning stable high beta tokamak equilibria

    International Nuclear Information System (INIS)

    Tuda, Takashi; Azumi, Masafumi; Kurita, Gen-ichi; Takizuka, Tomonori; Takeda, Tatsuoki

    1981-04-01

    The second stable regime of ballooning modes is numerically studied by using the two-dimensional tokamak transport code with the ballooning stability code. Using the simple FCT heating scheme, we find that the plasma can locally enter this second stable regime. And we obtained equilibria with fairly high beta (β -- 23%) stable against ballooning modes in a whole plasma region, by taking into account of finite thermal diffusion due to unstable ballooning modes. These results show that a tokamak fusion reactor can operate in a high beta state, which is economically favourable. (author)

  12. Energy storage for tokamak reactor cycles

    International Nuclear Information System (INIS)

    Buchanan, C.H.

    1979-01-01

    The inherent characteristic of a tokamak reactor requiring periodic plasma quench and reignition introduces the problem of energy storage to permit continuous electrical output to the power grid. The cycle under consideration in this paper is a 1000 second burn followed by a 100 second reignition phase. The physical size of a typical toroidal plasma reaction chamber for a tokamak reactor has been described earlier. The thermal energy storage requirements described in this reference will serve as a basis for much of the ensuing discussion

  13. Tokamak power systems studies, FY 1985

    International Nuclear Information System (INIS)

    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

  14. A Fast Shutdown Technique for Large Tokamaks

    International Nuclear Information System (INIS)

    Fredrickson, E.; Schmidt, G.L.; Hill, K.; Jardin, S.C.

    1999-01-01

    A practical method is proposed for the fast shutdown of a large ignited tokamak. The method consists of injecting a rapid series of 30-50 deuterium pellets doped with a small ( 0.0005%) concentration of Krypton impurity, and simultaneously ramping the plasma current and shaping fields down over a period of several seconds using the poloidal field system. Detailed modeling with the Tokamak Simulation Code using a newly developed pellet mass deposition model shows that this method should terminate the discharge in a controlled and stable way without producing significant numbers of runaway electrons. A partial prototyping of this technique was accomplished in TFTR

  15. Two-ion ICRF heating in Tokamaks

    International Nuclear Information System (INIS)

    Tennfors, E.

    1985-03-01

    The practical consequences for tokamak plasma heating in the ion cyclotron frequency regime of the two-dimensional treatment of the two-ion mode conversion layer are analyzed. The problem of evaluation of the condition for fast wave resonance is analyzed, as well as the limitations imposed by warm plasma effects. Simple ways to find the mode conversion surfaces when they exist are presented. Also for large tokamaks, it is possible to obtain mode conversion conditions for realistic antenna spectra provided species concentration and frequency are chosen such that the surface Epsilon = 0 intersects the plasma midplane just outside of the magnetic axis. (Author)

  16. Radial electric fields for improved tokamak performance

    International Nuclear Information System (INIS)

    Downum, W.B.

    1981-01-01

    The influence of externally-imposed radial electric fields on the fusion energy output, energy multiplication, and alpha-particle ash build-up in a TFTR-sized, fusing tokamak plasma is explored. In an idealized tokamak plasma, an externally-imposed radial electric field leads to plasma rotation, but no charge current flows across the magnetic fields. However, a realistically-low neutral density profile generates a non-zero cross-field conductivity and the species dependence of this conductivity allows the electric field to selectively alter radial particle transport

  17. Tokamak power systems studies, FY 1985

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Thermonuclear ignition in the next generation tokamaks

    International Nuclear Information System (INIS)

    Johner, J.

    1989-04-01

    The extrapolation of experimental rules describing energy confinement and magnetohydrodynamic - stability limits, in known tokamaks, allow to show that stable thermonuclear ignition equilibria should exist in this configuration, if the product aB t x of the dimensions by a magnetic-field power is large enough. Quantitative application of this result to several next-generation tokamak projects show that those kinds of equilibria could exist in such devices, which would also have enough additional heating power to promote an effective accessible ignition

  19. Shielding and maintainability in an experimental tokamak

    International Nuclear Information System (INIS)

    Abdou, M.A.; Fuller, G.; Hager, E.R.; Vogelsang, W.F.

    1979-01-01

    This paper presents the results of an attempt to develop an understanding of the various factors involved. This work was performed as a part of the task assigned to one of the expert groups on the International Tokamak Reactor (INTOR). However, the results of this investigation are believed to be generally applicable to the broad class of the next generation of experimental tokamak facilities such as ETF. The shielding penalties for requiring personnel access are quantified. This is followed by a quantitative estimate of the benefits associated with personnel access. The penalties are compared to the benefits and conclusions and recommendations are developed on resolving the issue

  20. Periodic disruptions in the MT-1 tokamak

    International Nuclear Information System (INIS)

    Zoletnik, S.

    1988-11-01

    Disruptive instabilities are common phenomena in toroidal devices, especially in tokamaks. Three types can be distinguished: internal, minor and major disruptions. Periodic minor disruptions in the MT-1 tokamak were measured systematically with values of the limiter safety factor between 4 and 10. The density limit as a function of plasma current and horizontal displacement was investigated. Precursor oscillations always appear before the instability with increasing amplitude but can be observed at the density limit with quasi-stationary amplitude. Phase correlation between precursor oscillations were measured with Mirnov coils and x-ray detectors, and they show good agreement with a simple magnetic island model. (R.P.) 11 refs.; 6 figs

  1. Gas blanket fueling of a tokamak reactor

    International Nuclear Information System (INIS)

    Gralnick, S.L.

    1978-01-01

    The purpose of this paper is a speculative investigation of the potential of fueling a Tokamak by introducing a sufficiently large quantity of gaseous deuterium and tritium at the vacuum wall boundary. It is motivated by two factors: current generation tokamaks are, in a manner of speaking, fueled from the edge quite successfully as is evidenced by pulse lengths that are long compared to particle recycling times, and by rapid plasma density increase produced by gas puffing, alternative, deep penetration fueling techniques that have been proposed possess severe technological problems and large costs

  2. Electronic system of TBR tokamak device

    International Nuclear Information System (INIS)

    Silva, R.P. da.

    1980-01-01

    The electronics developed as a part of the TBR project, which involves the construction of a small tokamak at the Physics Institute of the University of Sao Paulo, is described. On the basis of tokamak parameter values, the electronics for the toroidal field, ohmic/heating and vertical field systems is presented, including capacitors bank, switches, triggering circuits and power supplies. A controlled power oscilator used in discharge cleaning and pre-ionization is also described. The performance of the system as a function of the desired plasma parameters is discussed. (Author) [pt

  3. Tokamak Engineering Technology Facility scoping study

    International Nuclear Information System (INIS)

    Stacey, W.M. Jr.; Abdou, M.A.; Bolta, C.C.

    1976-03-01

    A scoping study for a Tokamak Engineering Technology Facility (TETF) is presented. The TETF is a tokamak with R = 3 m and I/sub p/ = 1.4 MA based on the counterstreaming-ion torus mode of operation. The primary purpose of TETF is to demonstrate fusion technologies for the Experimental Power Reactor (EPR), but it will also serve as an engineering and radiation test facility. TETF has several technological systems (e.g., superconducting toroidal-field coil, tritium fuel cycle, impurity control, first wall) that are prototypical of EPR

  4. Alfven wave heating in a tokamak reactor

    International Nuclear Information System (INIS)

    Borg, G.G.; Appert, K.; Knight, A.J.; Lister, J.B.; Vaclavik, J.

    1990-01-01

    A number of features of Alfven wave heating make it potentially attractive for use in large tokamak reactors. Among them are the availability and relativity low cost of the power supplies, the potential ability to act selectively on the current profile, and the probable absence of operational limits in size, fields or density. The physics of Alfven wave heating in a large tokamak is assessed. Present theoretical understanding of mode coupling and antenna loading is extrapolated to a large machine. The problem of a recessed antenna is analysed. Calculations of loading and discussion of various heating scenarios for the particular case of NET are also presented. (author). 23 refs, 18 figs, 4 tabs

  5. Can better modelling improve tokamak control?

    International Nuclear Information System (INIS)

    Lister, J.B.; Vyas, P.; Ward, D.J.; Albanese, R.; Ambrosino, G.; Ariola, M.; Villone, F.; Coutlis, A.; Limebeer, D.J.N.; Wainwright, J.P.

    1997-01-01

    The control of present day tokamaks usually relies upon primitive modelling and TCV is used to illustrate this. A counter example is provided by the successful implementation of high order SISO controllers on COMPASS-D. Suitable models of tokamaks are required to exploit the potential of modern control techniques. A physics based MIMO model of TCV is presented and validated with experimental closed loop responses. A system identified open loop model is also presented. An enhanced controller based on these models is designed and the performance improvements discussed. (author) 5 figs., 9 refs

  6. Increase in beta limit in tokamak plasmas

    International Nuclear Information System (INIS)

    Kamada, Yutaka

    2003-01-01

    This paper reviews recent studies of tokamak MHD stability towards the achievement of a high beta steady-state, where the profile control of current, pressure, and rotation, and the optimization of the plasma shape play fundamental roles. The key instabilities include the neoclassical tearing mode, the resistive wall mode, the edge localized mode, etc. In order to demonstrate an economically attractive tokamak reactor, it is necessary to increase the beta value simultaneously with a sufficiently high integrated plasma performance. Towards this goal, studies of stability control in self-regulating plasma systems are essential. (author)

  7. Development of Operation Scenario for Spherical Tokamak at SNU

    International Nuclear Information System (INIS)

    Sung, C. K.; Park, Y. S.; Lee, H. Y.; Kang, J.; Hwang, Y. S.

    2009-01-01

    Several concepts for nuclear fusion plant exist. In these concepts, tokamak is the most promising one to realize nuclear fusion plant. Though tokamak has leading concept, and this has world record in fusion heating power, tokamak has the critical drawback: low heating efficiency. That is the reason why we need another alternative concept which compensates tokamak's disadvantage. Spherical Torus(ST) is one of these kinds of concepts. ST is a kind of tokamak which has low aspect ratio. This feature gives ST advantages compared to conventional tokamak: high efficiency, compactness, low cost. However, ST lacks central region for solenoid that is needed to start-up and sustain. Since it is the most efficient that initializing and sustaining by using solenoid, this is ST's intrinsic limitation. To overcome this, a new device which can start-up and sustain ST plasmas by means of continuous tokamak plasma injection has been designed

  8. Tokamak startup: problems and scenarios related to the transient phases of ignited tokamak operations

    International Nuclear Information System (INIS)

    Sheffield, J.

    1985-01-01

    During recent years improvements have been made to tokamak startup procedures, which are important to the optimization of ignited tokamaks. The use of rf-assisted startup and noninductive current drive has led to substantial reduction and even complete elimination of the volt-seconds used during startup, relaxing constraints on poloidal coil, vacuum vessel, and structure design. This paper reviews these and other improvements and discusses the various bulk heating techniques that may be used to ignite a D-T plasma

  9. Reinforced spatial alternation as an animal model of obsessive-compulsive disorder (OCD): investigation of 5-HT2C and 5-HT1D receptor involvement in OCD pathophysiology.

    Science.gov (United States)

    Tsaltas, Eleftheria; Kontis, Dimitris; Chrysikakou, Sofia; Giannou, Haralambos; Biba, Angeliki; Pallidi, Stella; Christodoulou, Angeliki; Maillis, Antonis; Rabavilas, Andreas

    2005-05-15

    This study introduces a laboratory model of compulsive behavior based on persistence in the context of rewarded spatial alternation. Rats were screened for spontaneous persistence during T-maze reinforced alternation. Experiment 1: One high and one low spontaneous persistence group (n = 8) received 20 injections of fluoxetine, a matched pair saline, both followed by 4 days of meta-chlorophenylpiperazine (mCPP) challenge. Experiment 2: Five matched groups of rats (n = 9) received pretreatment (20 injections) with fluoxetine, mCPP, desipramine, diazepam or saline, followed by 4 days of mCPP challenge (fluoxetine in mCPP group). After washout, animals received 2 days of naratriptan, followed by another 2-day mCPP challenge. In both experiments mCPP significantly increased persistence in saline controls. Fluoxetine also acutely increased persistence scores: after a gradual return to baseline, these scores showed tolerance to mCPP. Experiment 1: This pattern was significant in high but not low initial persistence groups. Experiment 2: Fluoxetine and mCPP showed cross-tolerance. Neither desipramine nor diazepam protected against mCPP challenge. Persistence scores returned to baseline during washout and naratriptan and were thereafter increased by another mCPP challenge in all but the fluoxetine and mCPP groups, suggesting 5-HT2C receptor mediation. This model is based on spontaneous persistence behavior showing pharmacological responses concordant with those of compulsive symptomatology.

  10. Down-regulation of dopamine D-2, 5-HT2 receptors and β-adrenoceptors in rat brain after prolonged treatment with a new potential antidepressant, Lu 19-005

    International Nuclear Information System (INIS)

    Nowak, G.; Arnt, J.; Hyttel, J.; Svendsen, O.

    1985-01-01

    Lu 19-005 is a new phenylindan derivative with strong and equipotent inhibitory effect on dopamine (DA), noradrenaline (NA) and serotonin (5-HT) uptake. The adaptive effects of 2 weeks treatment with Lu 19-005, on receptor binding in vitro and on d-amphetamine responsiveness in vivo have been investigated in rats. One or 3 days after the final dose the number of β-adrenoceptors and of 5-HT 2 and DA D-2 receptors was decreased by 20-30%, whereas αsub1-adrenoceptor number was slightly decreased only 1 day after withdrawal. The DA D-2 receptor number remained decreased at 7 days withdrawal, but returned to normal after another 3 days. The brain levels of DA, NA and 5-HT were not changed by 2 weeks' Lu 19-005 treatment. The down-regulation of DA D-2 receptors was accompanied by tolerance to d-amphetamine-induced hypermotility (after low doses) and stereotyped licking or biting (after a high dose). The tolerance to d-amphetamine-induced hypermotility was maximal 3-5 days withdrawal time, and remained significant also 15 days after the last dose. The results are discussed in relation to the effect of prolonged treatment with other antidepressant drugs. (Author)

  11. A need for non-tokamak approaches to magnetic fusion energy

    International Nuclear Information System (INIS)

    Bathke, C.G.; Krakowski, R.A.; Miller, R.L.

    1992-01-01

    Focusing exclusively on conventional tokamak physics in the quest for commercial fusion power is premature, and the options for both advanced-tokamak and non-tokamak concepts need continued investigation. The basis for this claim is developed, and promising advanced-tokamak and non-tokamak options are suggested

  12. Tokamak startup with electron cyclotron heating

    International Nuclear Information System (INIS)

    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

  13. Transformer Recharging with Alpha Channeling in Tokamaks

    International Nuclear Information System (INIS)

    Fisch, N.J.

    2009-01-01

    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.

  14. Criteria for initiation of tokamak disruptions

    International Nuclear Information System (INIS)

    Hopcraft, K.I.; Turner, M.F.

    1986-01-01

    The process by which a tokamak plasma evolves from an equilibrium state containing a saturated magnetic island to one which is disruptively unstable is discussed and illustrated by numerical simulation of a resistive magnetoplasma. Those elements which are required to initiate a disruption are delineated

  15. Feedback stabilization of axisymmetric modes in tokamaks

    International Nuclear Information System (INIS)

    Jardin, S.C.; Larrabee, D.A.

    1982-01-01

    Noncircular tokamak plasmas can be unstable to ideal MHD axisymmetric instabilities. Passive conductors with finite resistivity will at best slow down these instabilities to the resistive (L/R) time of the conductors. An active feedback system far from the plasma which responds on this resistive time can stabilize the system provided its mutual inductance with the passive coils is small enough

  16. Compact tokamak reactors. Part 1 (analytic results)

    International Nuclear Information System (INIS)

    Wootton, A.J.; Wiley, J.C.; Edmonds, P.H.; Ross, D.W.

    1996-01-01

    We discuss the possible use of tokamaks for thermonuclear power plants, in particular tokamaks with low aspect ratio and copper toroidal field coils. Three approaches are presented. First we review and summarize the existing literature. Second, using simple analytic estimates, the size of the smallest tokamak to produce an ignited plasma is derived. This steady state energy balance analysis is then extended to determine the smallest tokamak power plant, by including the power required to drive the toroidal field, and considering two extremes of plasma current drive efficiency. The analytic results will be augmented by a numerical calculation which permits arbitrary plasma current drive efficiency; the results of which will be presented in Part II. Third, a scaling from any given reference reactor design to a copper toroidal field coil device is discussed. Throughout the paper the importance of various restrictions is emphasized, in particular plasma current drive efficiency, plasma confinement, plasma safety factor, plasma elongation, plasma beta, neutron wall loading, blanket availability and recirculating electric power. We conclude that the latest published reactor studies, which show little advantage in using low aspect ratio unless remarkably high efficiency plasma current drive and low safety factor are combined, can be reproduced with the analytic model

  17. Scattering measurements in Tokamak type devices

    International Nuclear Information System (INIS)

    Matoba, Tohru

    1975-03-01

    Theories, experiments and proposals for light scattering in Tokamak type devices are reviewed. Thomson scattering, measuring method of the current density distribution by scattering and resonance fluorescence are summarily described. These methods may be useful for diagnosis of the fusion plasmas. The report may help planning of the measuring apparatus for the fusion plasmas in future. (auth.)

  18. Maintenance considerations of the STARFIRE commercial tokamak

    International Nuclear Information System (INIS)

    Trachsel, C.A.; Zahn, H.S.; Field, R.E.; Stevens, H.C.

    1979-01-01

    This paper presents the maintenance approach, the commercial tokamak design features that enhance maintenance and preliminary repair time and required mean-time-between-failures for major subsystems. Reactor hall building and maintenance equipment requirements including hot cells, coil rewinding, and cranes are discussed

  19. Tokamak fusion test reactor. Final design report

    International Nuclear Information System (INIS)

    1978-08-01

    Detailed data are given for each of the following areas: (1) system requirements, (2) the tokamak system, (3) electrical power systems, (4) experimental area systems, (5) experimental complex, (6) neutral beam injection system, (7) diagnostic system, and (8) central instrumentation control and data acquisition system

  20. Tokamak power plant burn cycle options

    International Nuclear Information System (INIS)

    Ehst, D.A.

    1994-06-01

    Experiments show that tokamaks can operate in various fashions. Economic analyses show that steady state is most attractive provided the physics and technology of current drive (CD) can be modestly improved. Even with very conservative CD assumptions a hybrid operating mode seems superior to conventional, simple inductive operation

  1. Plasma-gun fueling for tokamak reactors

    International Nuclear Information System (INIS)

    Ehst, D.A.

    1980-11-01

    In light of the uncertain extrapolation of gas puffing for reactor fueling and certain limitations to pellet injection, the snowplow plasma gun has been studied as a fueling device. Based on current understanding of gun and plasma behavior a design is proposed, and its performance is predicted in a tokamak reactor environment

  2. Preliminary measurements on Tokamak KT-5

    International Nuclear Information System (INIS)

    Wen Yizhi; Wan Shude; Rong Furui; Haan Shengshen; Liu Wandong; Liu Lei

    1987-01-01

    A small tokamak, KT-5, has been put in to operation since 1984. The major and minor radius of the plasma are 30 and 4.5 cm, respectively. The parameters obtained in the first phase of KT-5 experiments are as follows B t = 0.45 T, I p ≥ 5 kA, q(α) σ = 50 eV

  3. Experimental methods to study tokamak plasma stability

    International Nuclear Information System (INIS)

    Perez-Navarro, A.

    1978-01-01

    Experimental devices to measure external instability modes with small pick-up coils to detect poloidal magnetic field fluctuations, and internal modes with soft-X-ray detectors are discussed. The characteristics of these devices are calculated for a small tokamak (R 0 = 30 cm, a = 10 cm, I 0 50 KA). (author)

  4. MHD stability of vertically asymmetric tokamak equilibria

    International Nuclear Information System (INIS)

    Dalhed, H.E.; Grimm, R.C.; Johnson, J.L.

    1981-03-01

    The ideal MHD stability properties of a special class of vertically asymmetric tokamak equilibria are examined. The calculations confirm that no major new physical effects are introduced and the modifications can be understood by conventional arguments. The results indicate that significant departures from up-down symmetry can be tolerated before the reduction in β becomes important for reactor operation

  5. [High beta tokamak research and plasma theory

    International Nuclear Information System (INIS)

    1990-01-01

    Our activities on High Beta Tokamak Research during the past 12 months of the present budget period can be divided into four areas: completion of kink mode studies in HBT; completion of carbon impurity transport studies in HBT; design of HBT-EP; and construction of HBT-EP. Each of these is described briefly in the sections of this progress report

  6. Computation of tokamak equilibria with steady flow

    International Nuclear Information System (INIS)

    Kerner, W.; Tokuda, Shinji

    1987-08-01

    The equations for ideal MHD equilibria with stationary flow are reexamined and addressed as numerically applied to tokamak configurations with a free plasma boundary. Both the isothermal (purely toroidal flow) and the poloidal flow cases are treated. Experiment-relevant states with steady flow (so far only in the toroidal direction) are computed by the modified SELENE40 code. (author)

  7. Ion diagnostics for the tokamak boundary

    International Nuclear Information System (INIS)

    Matthews, G.F.

    1991-01-01

    In this paper, recent developments in ion diagnostic probes for tokamak boundary plasmas are discussed. Three areas are covered: retarding field analysers, sniffer probes and plasma ion mass spectrometers. The contribution of these diagnostics to our understanding of plasma surface interactions is summarised. (author)

  8. Anomalous periodic disruptions in tokamak plasma

    International Nuclear Information System (INIS)

    Montvai, A.; Tegze, M.; Valyi, I.

    1982-09-01

    Anomalously strong, periodic instabilities were observed in the MT-1 tokamak. Characteristics of these instabilities were partly similar to those of internal disruptions, but there were features making them different from the normal relaxational oscillations. Basic characteristics of the phenomenon were studied with the aid of generally used diagnostics. (author)

  9. Energy confinement of high-density tokamaks

    NARCIS (Netherlands)

    Schüller, F.C.; Schram, D.C.; Coppi, B.; Sadowski, W.

    1977-01-01

    Neoclassical ion heat conduction is the major energy loss mechanism in the center of an ohmically heated high-d. tokamak discharge (n>3 * 1020 m-3). This fixes the mutual dependence of plasma quantities on the axis and leads to scaling laws for the poloidal b and energy confinement time, given the

  10. Supravodivý tokamak dobyl Asii

    Czech Academy of Sciences Publication Activity Database

    Řípa, Milan

    2006-01-01

    Roč. 54, č. 18 (2006), s. 58 ISSN 0040-1064 Institutional research plan: CEZ:AV0Z20430508 Keywords : superconducting tokamak * ITER * Tore Supra * Institute of Plasma Physics AV CR Subject RIV: BL - Plasma and Gas Discharge Physics

  11. Runaway electrons in the TRIAM-1 tokamak

    International Nuclear Information System (INIS)

    Satoh, Takemichi; Nakamura, Kazuo; Toi, Kazuo; Nakamura, Yukio; Hiraki, Naoji

    1981-01-01

    Pulse height analysis of soft X-rays is carried out in the TRIAM-1 tokamak. The electron temperatures determined from the soft X-ray spectrum agree well with those from Thomson scattering. It is observed that low-energy runaway (slideaway) electrons appear in the high-current-density discharges. (author)

  12. Runaway electrons in the TRIAM-1 tokamak

    Energy Technology Data Exchange (ETDEWEB)

    Satoh, T; Nakamura, K; Toi, K; Nakamura, Y; Hiraki, N [Kyushu Univ., Fukuoka (Japan). Research Inst. for Applied Mechanics

    1981-09-01

    Pulse height analysis of soft X-rays is carried out in the TRIAM-1 tokamak. The electron temperatures determined from the soft X-ray spectrum agree well with those from Thomson scattering. It is observed that low-energy runaway (slideaway) electrons appear in the high-current-density discharges.

  13. Plasma position control in SST1 tokamak

    Indian Academy of Sciences (India)

    also placed inside the vessel, however the controller would ignore fast but insignificant changes in radius arising ... poloidal cross-sectional view of the SST1 plasma along with the stabilizers are shown in figure 1 and ... [1] model which has shown excellent agreement with control experiments in TCV tokamak and also with ...

  14. Central control system for the EAST tokamak

    International Nuclear Information System (INIS)

    Sun Xiaoyang; Ji Zhenshan; Wu Yicun; Luo Jiarong

    2008-01-01

    The architecture, the main function and the design scheme of the central control system and the collaboration system of EAST tokamak are described. The main functions of the central control system are to supply a union control interface for all the control, diagnoses, and data acquisition (DAQ) subsystem and it is also designed to synchronize all those subsystem. (authors)

  15. Microinstabilities in weak density gradient tokamak systems

    International Nuclear Information System (INIS)

    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

  16. Design parameters of Tokamak-7 system

    International Nuclear Information System (INIS)

    Ivanov, D.P.; Keilin, V.E.; Klimenko, E.Yu.; Strelkov, V.S.

    Superconducting windings for the main magnetic field of Tokamak-7 are discussed. The parameters of this facility are based on the use of commercially available superconducting materials for fields up to 80 kOe. Experimental parameters are described. (U.S.)

  17. Modular pulse sequencing in a tokamak system

    International Nuclear Information System (INIS)

    Chew, A.C.; Lee, S.; Saw, S.H.

    1992-01-01

    Pulse technique applied in the timing and sequencing of the various part of the MUT tokamak system are discussed. The modular architecture of the pulse generating device highlights the versatile application of the simple physical concepts in precise and complicated research experiment. (author)

  18. INTEGRATED PLASMA CONTROL FOR ADVANCED TOKAMAKS

    International Nuclear Information System (INIS)

    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.

    2004-03-01

    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

  19. Tokamak startup with electron cyclotron heating

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. The ARIES tokamak fusion reactor study

    International Nuclear Information System (INIS)

    Bartlit, J.R.; Bathke, C.G.; Krakowski, R.A.; Miller, R.L.; Beecraft, W.R.; Hogan, J.T.; Peng, Y.K.M.; Reid, R.L.; Strickler, D.J.; Whitson, J.C.; Blanchard, J.P.; Emmert, G.A.; Santarius, J.F.; Sviatoslavsky, I.N.; Wittenberg, L.J.

    1989-01-01

    The ARIES study is a community effort to develop several visions of the tokamak as fusion power reactors. The aims are to determine their potential economics, safety, and environmental features and to identify physics and technology areas with the highest leverage for achieving the best tokamak reactor. Three ARIES visions are planned, each having a different degree of extrapolation from the present data base in physics and technology. The ARIES-I design assumes a minimum extrapolation from current tokamak physics (e.g., 1st stability) and incorporates technological advances that can be available in the next 20 to 30 years. ARIES-II is a DT-burning tokamak in 2nd stability regime and employs both potential advances in the physics and expected advances in technology and engineering; and ARIES-III is a conceptual D 3 He reactor. This paper focuses on the ARIES-I design. Parametric systems studies show that the optimum 1st stability tokamak has relatively low plasma current (∼ 12 MA), high plasma aspect ratio (∼ 4-6), and high magnetic field (∼ 24 T at the coil). ARIES-I is 1,000 MWe (net) reactor with a plasma major radius of 6.5 m, a minor radius of 1.4 m, a neutron wall loading of about 2.8 MW/m 2 , and a mass power density of about 90 kWe/ton. The ARIES-I reactor operates at steady state using ICRF fast waves to drive current in the plasma core and lower-hybrid waves for edge-plasma current drive. The current-drive system supplements a significant (∼ 57%) bootstrap current contribution. The impurity control system is based on high-recycling poloidal divertors. Because of the high field and large Lorentz forces in the toroidal-field magnets, innovative approaches with high-strength materials and support structures are used. 24 refs., 4 figs., 1 tab

  1. Plea for stellarator funding raps tokamaks

    International Nuclear Information System (INIS)

    Blake, M.

    1992-01-01

    The funding crunch in magnetic confinement fusion development has moved the editor of a largely technical publication to speak out on a policy issue. James A. Rome, who edits Stellarator News from the Fusion Energy Division at Oak Ridge National Laboratory, wrote an editorial that appeared on the front page of the May 1992 issue. It was titled open-quotes The US Stellarator Program: A Time for Renewal,close quotes and while it focused chiefly on that subject (and lamented the lack of funding for the operation of the existing ATF stellarator at Oak Ridge), it also cited some of the problems inherent in the mainline MCF approach--the tokamak--and stated that if the money can be found for further tokamak design upgrades, it should also be found for stellarators. Rome wrote, open-quotes There is growing recognition in the US, and elsewhere, that the conventional tokamak does not extrapolate to a commercially competitive energy source except with very high field coils ( 1000 MWe).close quotes He pointed up open-quotes the difficulty of simultaneously satisfying conflicting tokamak requirements for efficient current drive, high bootstrap-current fraction, complete avoidance of disruptions, adequate beta limits, and edge-plasma properties compatible with improved (H-mode) confinement and acceptable erosion of divertor plates.close quotes He then called for support for the stellarator as open-quotes the only concept that has performance comparable to that achieved in tokamaks without the plasma-current-related limitations listed above.close quotes

  2. International tokamak reactor conceptual design overview

    International Nuclear Information System (INIS)

    Stacey, W.M. Jr.

    1983-01-01

    The International Tokamak Reactor (INTOR) Workshop is an unique collaborative effort among Euratom, Japan, the USA and the USSR, under the auspices of the IAEA, to assess, define, design, construct and operate the next major experiment in the World Tokamak Program beyond the TFTR, JET, JT-60, T-15 generation. During the Zero-Phase (1979), a technical data base assessment was performed, leading to a positive assessment of feasibility. During Phase-I (1/80-6/81), a conceptual design was developed to define the concept. The programmatic objectives are that INTOR should: (1) be the maximum reasonable step beyond the TFTR, JET, JT-60, T-15 generation of tokamaks, (2) demonstrate the plasma performance required for tokamak DEMOs, (3) test the development and integration into a reactor system of those technologies required for a DEMO, (4) serve as a test facility for blanket, tritium production, materials, and plasma engineering technology, (5) test fusion reactor component reliability, (6) test the maintainability of a fusion reactor, and (7) test the factors affecting the reliability, safety and environmental acceptability of a fusion reactor. A conceptual design has been developed to define a device which is consistent with these objectives. The design concept could, with a reasonable degree of confidence, be developed into a workable engineering design of a tokamak that met the performance objectives of INTOR. There is some margin in the design to allow for uncertainty. While design solutions have been found for all of the critical issues, the overall design may not yet be optimal. (author)

  3. Involvement of 5-HT(2) serotonergic receptors of the nucleus raphe magnus and nucleus reticularis gigantocellularis/paragigantocellularis complex neural networks in the antinociceptive phenomenon that follows the post-ictal immobility syndrome.

    Science.gov (United States)

    de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Ferreira, Célio Marcos Dos Reis; Coimbra, Norberto Cysne

    2006-09-01

    The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and men. In this interesting post-ictal behavioral response, endogenous opioid peptides-mediated mechanisms, as well as cholinergic-mediated antinociceptive processes, have been suggested. However, considering that many serotonergic descending pathways have been implicated in antinociceptive reactions, the aim of the present work is to investigate the involvement of 5-HT(2)-serotonergic receptor subfamily in the post-ictal antinociception. The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. Convulsions were followed by statistically significant increase in the tail-flick latencies (TFL), at least for 120 min of the post-ictal period. Male Wistar rats were submitted to stereotaxic surgery for introduction of a guide-cannula in the rhombencephalon, aiming either the nucleus raphe magnus (NRM) or the gigantocellularis complex. In independent groups of animals, these nuclei were neurochemically lesioned with a unilateral microinjection of ibotenic acid (1.0 microg/0.2 microL). The neuronal damage of either the NRM or nucleus reticularis gigantocellularis/paragigantocellularis complex decreased the post-ictal analgesia. Also, in other independent groups, central administration of ritanserin (5.0 microg/0.2 microL) or physiological saline into each of the reticular formation nuclei studied caused a statistically significant decrease in the TFL of seizing animals, as compared to controls, in all post-ictal periods studied. These results indicate that serotonin input-connected neurons of the pontine and medullarly reticular nuclei may be involved in the post-ictal analgesia.

  4. An overview on plasma disruption mitigation and avoidance in tokamak

    International Nuclear Information System (INIS)

    He Kaihui; Pan Chuanhong; Feng Kaiming

    2002-01-01

    Plasma disruption, which seems to be unavoidable in Tokamak operation, occurs very fast and uncontrolled. In order to keep Tokamak plasma from disruption and mitigate the disruption frequency, the research on Tokamak plasma major disruption constitutes one of the main topics in plasma physics. The phenomena and processes of the precursor, thermal quench, current quench, VDE, halo current and runaway electrons generation during plasma disruption are analyzed in detail and systematically based on the data obtained from current Tokamaks such as TFTR, JET, JT-60U and ASDEX-U, etc. The methods to mitigate and avoid disruption in Tokamak are also highlighted schematically. Therefore, it is helpful and instructive for plasma disruption research in next generation large Tokamak such as ITER-FEAT

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  6. Disruption generated secondary runaway electrons in present day tokamaks

    International Nuclear Information System (INIS)

    Pankratov, I.M.; Jaspers, R.

    2000-01-01

    An analysis of the runaway electron secondary generation during disruptions in present day tokamaks (JET, JT-60U, TEXTOR) was made. It was shown that even for tokamaks with the plasma current I approx 100 kA the secondary generation may dominate the runaway production during disruptions. In the same time in tokamaks with I approx 1 MA the runaway electron secondary generation during disruptions may be suppressed

  7. Tokamak residual zonal flow level in near-separatrix region

    International Nuclear Information System (INIS)

    Bing-Ren, Shi

    2010-01-01

    Residual zonal flow level is calculated for tokamak plasmas in the near-separatrix region of a diverted tokamak. A recently developed method is used to construct an analytic divertor tokamak configuration. It is shown that the residual zonal flow level becomes smaller but still keeps finite near the separatrix because the neoclassical polarisation mostly due to the trapped particles goes larger in this region. (fluids, plasmas and electric discharges)

  8. Steady State Advanced Tokamak (SSAT): The mission and the machine

    International Nuclear Information System (INIS)

    Thomassen, K.; Goldston, R.; Nevins, B.; Neilson, H.; Shannon, T.; Montgomery, B.

    1992-03-01

    Extending the tokamak concept to the steady state regime and pursuing advances in tokamak physics are important and complementary steps for the magnetic fusion energy program. The required transition away from inductive current drive will provide exciting opportunities for advances in tokamak physics, as well as important impetus to drive advances in fusion technology. Recognizing this, the Fusion Policy Advisory Committee and the US National Energy Strategy identified the development of steady state tokamak physics and technology, and improvements in the tokamak concept, as vital elements in the magnetic fusion energy development plan. Both called for the construction of a steady state tokamak facility to address these plan elements. Advances in physics that produce better confinement and higher pressure limits are required for a similar unit size reactor. Regimes with largely self-driven plasma current are required to permit a steady-state tokamak reactor with acceptable recirculating power. Reliable techniques of disruption control will be needed to achieve the availability goals of an economic reactor. Thus the central role of this new tokamak facility is to point the way to a more attractive demonstration reactor (DEMO) than the present data base would support. To meet the challenges, we propose a new ''Steady State Advanced Tokamak'' (SSAT) facility that would develop and demonstrate optimized steady state tokamak operating mode. While other tokamaks in the world program employ superconducting toroidal field coils, SSAT would be the first major tokamak to operate with a fully superconducting coil set in the elongated, divertor geometry planned for ITER and DEMO

  9. Summary of the 1982 small tokamak users meeting

    International Nuclear Information System (INIS)

    Sprott, J.C.

    1982-11-01

    On November 1, 1982, the sixth in a series of approximately annual meetings of the users of small tokamaks was held in conjunction with the APS Division of Plasma Physics meeting at New Orleans. The meeting lasted three hours, with 34 people attending. The interest was on strengthening the ties between the small tokamaks and the large tokamaks. Accordingly, the latest meeting was dedicated to this theme, and in contrast to previous meetings, a few representatives from the large tokamaks were invited to attend and make presentations. Summaries of the various talks are included

  10. Numerical studies of edge localized instabilities in tokamaks

    International Nuclear Information System (INIS)

    Wilson, H.R.; Snyder, P.B.; Huysmans, G.T.A.; Miller, R.L.

    2002-01-01

    A new computational tool, edge localized instabilities in tokamaks equilibria (ELITE), has been developed to help our understanding of short wavelength instabilities close to the edge of tokamak plasmas. Such instabilities may be responsible for the edge localized modes observed in high confinement H-mode regimes, which are a serious concern for next step tokamaks because of the high transient power loads which they can impose on divertor target plates. ELITE uses physical insight gained from analytic studies of peeling and ballooning modes to provide an efficient way of calculating the edge ideal magnetohydrodynamic stability properties of tokamaks. This paper describes the theoretical formalism which forms the basis for the code

  11. Start of the international tokamak physics activity

    International Nuclear Information System (INIS)

    Campbell, D.

    2001-01-01

    This newsletter comprises a summary on the start of the International Tokamak Physics activity (ITPA) by Dr. D. Campbell, Chair of the ITPA Co-ordinating Committee. As the ITER EDA drew to a close, it became clear that it was desirable to establish a new mechanism in order to promote the continued development of the physics basis for burning plasma experiments and to preserve the invaluable collaborations between the major international fusion communities which had been established through the ITER physics expert groups. As a result of the discussions of the representatives of the European Union, Japan, the Russian Federation and the United States the agreed principles for conducting the International Tokamak Physics Activity (ITPA) were elaborated and ITPA topical physics groups were organized

  12. Assembly study for JT-60SA tokamak

    Energy Technology Data Exchange (ETDEWEB)

    Shibanuma, K., E-mail: shibanuma.kiyoshi@jaea.go.jp [Japan Atomic Energy Agency, Naka, Ibaraki-ken 311-0193 (Japan); Arai, T.; Hasegawa, K.; Hoshi, R.; Kamiya, K.; Kawashima, H.; Kubo, H.; Masaki, K.; Saeki, H.; Sakurai, S.; Sakata, S.; Sakasai, A.; Sawai, H.; Shibama, Y.K.; Tsuchiya, K.; Tsukao, N.; Yagyu, J.; Yoshida, K.; Kamada, Y. [Japan Atomic Energy Agency, Naka, Ibaraki-ken 311-0193 (Japan); Mizumaki, S. [Toshiba Corporation, Minato-ku, Tokyo 105-8001 (Japan); and others

    2013-10-15

    The assembly scenarios and assembly tools of the major tokamak components for JT-60SA are studied in the following. (1) The assembly frame (with a dedicated 30-tonne crane), which is located around the JT-60SA tokamak, is adopted for effective assembly works in the torus hall and the temporary support of the components during assembly. (2) Metrology for precise positioning of the components is also studied by defining the metrology points on the components. (3) The sector segmentation for weld joints and positioning of the vacuum vessel (VV), the assembly scenario and tools for VV thermal shield (TS), the connection of the outer intercoil structure (OIS) and the installation of the final toroidal field coil (TFC) are studied, as typical examples of the assembly scenarios and tools for JT-60SA.

  13. Module description of TOKAMAK equilibrium code MEUDAS

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Masaei; Hayashi, Nobuhiko; Matsumoto, Taro; Ozeki, Takahisa [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment

    2002-01-01

    The analysis of an axisymmetric MHD equilibrium serves as a foundation of TOKAMAK researches, such as a design of devices and theoretical research, the analysis of experiment result. For this reason, also in JAERI, an efficient MHD analysis code has been developed from start of TOKAMAK research. The free boundary equilibrium code ''MEUDAS'' which uses both the DCR method (Double-Cyclic-Reduction Method) and a Green's function can specify the pressure and the current distribution arbitrarily, and has been applied to the analysis of a broad physical subject as a code having rapidity and high precision. Also the MHD convergence calculation technique in ''MEUDAS'' has been built into various newly developed codes. This report explains in detail each module in ''MEUDAS'' for performing convergence calculation in solving the MHD equilibrium. (author)

  14. Neural net prediction of tokamak plasma disruptions

    International Nuclear Information System (INIS)

    Hernandez, J.V.; Lin, Z.; Horton, W.; 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

  15. International tokamak reactor conceptual design overview

    International Nuclear Information System (INIS)

    Stacey, W.M. Jr.

    1981-01-01

    The International Tokamak Reactor (INTOR) Workshop is an unique collaborative effort among Euratom, Japan, the USA and USSR. The Zero-Phase of the INTOR Workshop, which was conducted during 1979, assessed the technical data base that would support the construction of the next major device in the tokamak program to operate in the early 1990s and defined the objectives and characteristics of this device. The INTOR workshop was extended into phase-1, the Definition Phase, in early 1980. The objective of the Phase-1 Workshop was to develop a conceptual design of the INTOR experiment. The purpose of this paper is to give an overview of the work of the Phase-1 INTOR Workshop (January 1980-June 1981, with emphasis upon the conceptual design

  16. Magnetohydrodynamic stability of tokamak edge plasmas

    International Nuclear Information System (INIS)

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

    1998-01-01

    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 Hclose 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 ∼n 1/3 rational surfaces into the plasma (rather than ∼n 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

  17. The physics of tokamak start-up

    International Nuclear Information System (INIS)

    Mueller, D.

    2013-01-01

    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

  18. Rapidly Moving Divertor Plates In A Tokamak

    International Nuclear Information System (INIS)

    Zweben, S.

    2011-01-01

    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.

  19. The tokamak - an imperfect frame of refernce

    International Nuclear Information System (INIS)

    Schmitter, K.U.

    1981-03-01

    It is attempted to assess the suitability of tokamaks for fusion power plants on the basis of existing design studies by reference to the reality of energy production in fission power plants. A definition of suitability criteria and a discussion of their relation to the most important features of power plants are followed by a comparative treatment. For example, the mean volumetric net electric power density in the nuclear islands of tokamak power plant designs is only 2,5 to 4 E of the value common today in light water reactor nuclear islands. In addition, configuration problems, auxiliary power requirements and energy payback time are discussed and taken into account in the assessment. (orig.)

  20. Tokamak Fusion Core Experiment maintenance study

    International Nuclear Information System (INIS)

    Snyder, A.M.; Watts, K.D.

    1985-01-01

    The recently completed Tokamak Fusion Core Experiment (TFCX) design project was carried out to investigate potential next generation tokamak concepts. An important aspect of this project was the early development and incorporation of remote maintainability throughout the design process. This early coordination and incorporation of maintenance aspects to the design of the device and facilities would assure that the machine could ultimately be maintained and repaired in an efficient and cost effective manner. To meet this end, a rigorously formatted engineering trade study was performed to determine the preferred configuration for the TFCX reactor based primarily on maintenance requirements. The study indicated that the preferred design was one with an external vacuum vessel and torrodial field coils that could be removed via a simple radial motion. The trade study is presented and the preferred TFCX configuration is described