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Adam, M., primary, Alpert, Nathaniel M., additional, Anderson, J.R., additional, Andreasen, Nancy C., additional, Antonini, A., additional, Ardekani, Babak A., additional, Arndt, Stephan, additional, Ashburner, John, additional, Ashworth, Sharon, additional, Bailey, Dale L., additional, Baker, E., additional, Barnes, D.G., additional, Bench, C., additional, Bendriem, B., additional, Berdichevsky, D., additional, Biegon, A., additional, Blair, R.C., additional, Blomqvist, G., additional, Bloomfield, Peter M., additional, Ponto, Laura L. Boles, additional, Brakeman, Paul, additional, Braun, Michael, additional, Brooks, David J., additional, Brown, C.K., additional, Brown, W.D., additional, Bruckbauer, T., additional, Buckley, K.R., additional, Calonder, C., additional, Campbell, Gregory, additional, Carson, Richard E., additional, Chaly, Thomas, additional, Chan, G. L-Y., additional, Chen, Chin-Tu, additional, Cizadlo, Ted, additional, Cliffe, I.A., additional, Collins, D.L., additional, Cooper, Malcolm, additional, Crivello, F., additional, Crossnoe, M., additional, Cumming, Paul, additional, Cunningham, Vincent J., additional, Czernin, J., additional, Dahlbom, M., additional, Damasio, H., additional, DaSilva, J., additional, Witherspoon, Margaret E. Daube-, additional, DeJesus, O.T., additional, Delforge, J., additional, Dhawan, Vijay, additional, Dickhoven, S., additional, Diksic, Mirko, additional, Eberl, Stefan, additional, Egan, G.F., additional, Eidelberg, David, additional, Eriksson, Lars, additional, Evans, Alan C., additional, Fink, G.R., additional, Fischman, Alan J., additional, Fisher, Ronald E., additional, Fletcher, A., additional, Fontaine, A., additional, Ford, I., additional, Forse, G., additional, Frackowiak, R.S.J., additional, Frank, R.J., additional, Friston, K.J., additional, Frost, J. James, additional, Frouin, V., additional, Fujita, Hideaki, additional, Fujiwara, Takehiko, additional, Fukuda, H., additional, Fulham, Michael J., additional, Gee, Anthony D., additional, Gillings, N., additional, Gjedde, Albert, additional, Glaser, Robert, additional, Grabowski, T.J., additional, Graf, R., additional, Grafton, S.T., additional, Graham, Michael M., additional, Grasby, P., additional, Gunn, R.N., additional, Günther, I., additional, Hagisawa, S., additional, Haida, A., additional, Halber, M., additional, Hallett, Mark, additional, Hansen, Lars K., additional, Harris, Greg, additional, Haslam, Jane, additional, Hasselbalch, Steen, additional, Hatazawa, Jun, additional, Heiss, W.-D., additional, Herholz, K., additional, Herscovitch, Peter, additional, Herzog, H., additional, Hichwa, Richard D., additional, Hoh, C., additional, Holden, J.E., additional, Holm, Søren, additional, Holmes, A.P., additional, Holmes, C.J., additional, Hooper, Patrick K., additional, Houle, S., additional, Houser, D., additional, Huang, Sung-Cheng, additional, Hume, S.P., additional, Hurtig, Richard R., additional, Hussey, D., additional, Hutton, Brian F., additional, Iacoboni, M., additional, Ido, T., additional, Iida, Hidehiro, additional, Inoue, O., additional, Ishii, Kazunari, additional, Ishikawa, Tatsuya, additional, Itoh, H., additional, Itoh, Masatoshi, additional, Iwata, R., additional, Jadali, F., additional, Jagust, W., additional, Jivan, S., additional, Joliot, M., additional, Jones, A.K.P., additional, Jones, C., additional, Jones, Terry, additional, Kanno, Iwao, additional, Kao, Chien-Min, additional, Kapur, S., additional, Karbe, H., additional, Kessler, J., additional, Kilbourn, Michael R., additional, Kimura, Yuichi, additional, Kinahan, P.E., additional, Knorr, U., additional, Kobayashi, K., additional, Kops, E. Rota, additional, Kosugi, Yukio, additional, Kruger, Mark, additional, Kuwabara, Hiroto, additional, Lammertsma, Adriaan A., additional, Laurier, L., additional, Law, Ian, additional, Leenders, K.L., additional, Legg, B., additional, Levin, Z., additional, Lin, Kang-Ping, additional, Links, Jonathan M., additional, Lipinski, B., additional, Lopresti, B.J., additional, Löttgen, J., additional, Luthra, S.K., additional, Ma, Yilong, additional, Maguire, R.P., additional, Mahmood, K., additional, Malizia, Andrea L., additional, Mankoff, David A., additional, Marenco, Stefano, additional, Marrett, S., additional, Mathis, C.A., additional, Matsumura, Y., additional, Mazoyer, B., additional, Mazziotta, John C., additional, McCarron, J.A., additional, Meguro, K., additional, Meikle, Steven R., additional, Mejia, Marco A., additional, Mellet, E., additional, Meltzer, Carolyn Cidis, additional, Meyer, Ernst, additional, Millet, P., additional, Minoshima, S., additional, Mintun, M.A., additional, Missimer, J., additional, Miura, Shuichi, additional, Miyake, M., additional, Momose, Toshimitsu, additional, Mørch, Niels, additional, Morris, Evan D., additional, Morrish, Paul K., additional, Morrison, S., additional, Müller-Gärtner, H.W., additional, Murase, Kenya, additional, Muzi, Mark, additional, Myers, R., additional, Nakamura, Takashi, additional, Nariai, Tadashi, additional, Neelin, P., additional, Nickles, R.J., additional, Nishikawa, Junichi, additional, Nishizawa, Sadahiko, additional, Nutt, D.J., additional, O'Keefe, G.J., additional, O'Leary, Daniel S., additional, O'Sullivan, B.T., additional, O'Sullivan, Finbarr, additional, Oberschelp, W., additional, Ogawa, Toshihide, additional, Ono, S., additional, Osman, S., additional, Patlak, Clifford, additional, Paulson, Olaf B., additional, Pawlik, Gunter, additional, Petit, L., additional, Pietrzyk, U., additional, Pike, V.W., additional, Poline, J.-B., additional, Poole, K., additional, Price, J.C., additional, Psylla, M., additional, Pyzalski, Robert, additional, Rajeswaran, S., additional, Rakshi, James S., additional, Ranicar, Alex, additional, Rauch, Scott L., additional, Remy, P., additional, Reutens, David C., additional, Roberts, Andy, additional, Rosenqvist, G., additional, Rottenberg, D.A., additional, Rousset, Olivier G., additional, Ruth, T.J., additional, Sadato, Norihiro, additional, Samson, Y., additional, Sasaki, H., additional, Sase, Mikiya, additional, Sashin, D., additional, Schaper, K., additional, Schlaug, G., additional, Schnorr, L., additional, Seitz, R.J., additional, Senda, Michio, additional, Shelton, S.E., additional, Shields, Anthony F., additional, Shimosegawa, Eku, additional, Shiraishi, Masahiro, additional, Shrager, Richard, additional, Sidtis, J.J., additional, Simpson, N.R., additional, Smith, D., additional, Smith, Donald F., additional, Snow, B.J., additional, Snyder, Abraham Z., additional, Sossi, V., additional, Spelle, L., additional, Spence, Alexander, additional, Strother, S.C., additional, Stumpf, Martin J., additional, Suganami, Yusuke, additional, Svarer, Claus, additional, Swerdloff, S.J., additional, Syrota, A., additional, Taguchi, A., additional, Talarico, E., additional, Taylor, Chris, additional, Tellman, L., additional, Thiel, A., additional, Danguy, H. J. Tochon-, additional, Toga, Arthur W., additional, Toussaint, P.-J., additional, Townsend, D.W., additional, Toyama, Hinako, additional, Trébossen, R., additional, Tzourio, N., additional, Uchiyama, A., additional, Uemura, Kazuo, additional, Uno, H., additional, Vafaee, M., additional, Vingerhoets, F.J.G., additional, Vontobel, P., additional, Wagner, R., additional, Watabe, Hiroshi, additional, Watkins, G. Leonard, additional, Watson, J.D.G., additional, Wernick, Miles, additional, Wienhard, K., additional, Wilson, A.A., additional, Wilson, S., additional, Wollenweber, Scott D., additional, Wong, Dean F., additional, Woods, Roger P., additional, Worsley, K.J., additional, Yan, Yuchen, additional, Yanai, K., additional, Yang, J., additional, Yap, Jeffrey T., additional, Yu, D.C., additional, Zeien, Gene, additional, Zhou, Y., additional, and Zubieta, Jon Kar, additional

Published
1996
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83. Brain Regional [Alpha]-[[sup.11]C]Methyl-L-Tryptophan Trapping in Impulsive Subjects With Borderline Personality Disorder

Author

Leyton, Marco, Okazawa, Hidehiko, Diksic, Mirko, Paris, Joel, Rosa, Pedro, Mzengeza, Shadreck, Young, Simon N., Blier, Pierre, and Benkelfat, Chawki

Subjects
Serotonin -- Physiological aspects, Impulsive personality -- Causes of, Tryptophan -- Physiological aspects, Health, Psychology and mental health
Abstract

Objective: Neurotransmission of serotonin (or 5-hydroxytryptamine [5-HT]) is thought to be disturbed in patients exhibiting impulsive behaviors. However, until recently it has not been possible to test this hypothesis in the brains of living humans. Method: Unidirectional trapping of the 5-HT precursor analog [Alpha]-[[sup.11]C]methyl-L-tryptophan ([Alpha]-[[sup.11]C]MTrp) has been proposed as an index of 5-HT synthesis capacity. The authors measured brain regional [Alpha]-[[sup.11]C]MTrp trapping with positron emission tomography in medication-free subjects with borderline personality disorder (N=13) and a healthy comparison group (N=11). Impulsivity was assessed by using a laboratory measure of behavioral disinhibition, go/no-go commission errors. Results: Compared to healthy men, the men with borderline personality disorder had significantly lower [Alpha]-[[sup.11]C]MTrp trapping in corticostriatal sites, including the medial frontal gyrus, anterior cingulate gyrus, superior temporal gyrus, and corpus striatum. In the women with borderline personality disorder, significantly lower [Alpha][[sup.11]C]MTrp trapping was seen in fewer regions, but in both men and women, negative correlations with impulsivity scores were identified in the medial frontal gyrus, anterior cingulate gyrus, temporal gyrus, and striatum. Conclusions: Low 5-HT synthesis capacity in corticostriatal pathways may contribute to the development of impulsive behaviors in persons with borderline personality disorder. (Am J Psychiatry 2001; 158:775-782)

Published
2001

87. Acute effect of monoamine oxidase (MAO) inhibitors on the 5-HT synthesis rate in the rat brain: an autoradiographic study

Author

Muck-Šeler, Dorotea, Pivac, Nela, Diksic, Mirko, and Bousquet, Pascal

Subjects
clorgyline, deprenyl, pargyline, serotonin synthesis rate
Abstract

The aim of the present study was to examine the effect of acute administration of three irreversible MAO inhibitors: clorgyline (MAO A inhibitor), deprenyl (MAO B inhibitor) and pargyline (MAO A/B inhibitor) on the serotonin (5-HT) synthesis rate, measured in 28 regions of the rat brain using an autoradiographic method and alpha-14C-methyl-L-tryptophan as a tracer. Clorgyline (10 mg/kg), deprenyl (3 mg/kg) and pargyline (100 mg/kg) significantly decreased 5-HT synthesis rate in the dorsal (-18%, -20%; -20%), median (-27%; -41%; -29%) raphe and pineal body (-31%; -71%; -32%), respectively. Clorgyline increased 5-HT synthesis rate in sensory-motor cortex (+37%), lateral caudate (+37%) and ventral hippocampus (+36%). This significant change in the 5-HT synthesis rate, was even more expressed in the regions of superior olive (+81%), frontal (+86%) and sensory-motor (+52%) cortex, medial forebrain bundle (+44%) and medial geniculate body (+44%) of pargyline treated rats. Deprenyl did not change the rate of 5-HT synthesis in the areas of nerve terminals. Results suggest that the increase in 5-HT concentrations after inhibition of MAO activity has different effect on the 5-HT synthesis rate in the serotonergic cell bodies and areas of nerve terminals. MAO A and in less extend MAO B are directly and/or indirectly involved in the regulation of 5-HT synthesis throughout the brain. Supported by the MRC of Canada (MT-13368), US Public Service (R01-NS19629) and Croatian Ministry of Science.

Published
2001

88. Acute effects of noradrenaline and serotonin (5-HT)uptake inhibitors (desipramine and fluoxetine)on the 5-HT synthesis rate in the rat brain regions : an autoradiographic study

Author

Pivac, Nela, Muck-Šeler, Dorotea, Diksic, Mirko, Mendlewicz, J., and Souery, D.

Subjects
serotonin synthesis rate, rat brain regions, desipramine, fluoxetine, autoradiography
Abstract

Various studies have implicated the involvement of noradrenaline and/or serotonin (5-HT) in the pathogenesis and treatment of depression. Since noradrenaline uptake inhibitor (desipramine) and 5-HT uptake inhibitor (fluoxetine) are antidepressants, the aim of the present study was to compare the acute effects of both drugs on the rate of 5-HT synthesis in the rat brain by an original autoradiographic method (Diksic et al 1990), using a-14C-methyl-L-tryptophan (specific activity 55 mCi/mmol) as a tracer (30 mCi). The administration of desipramine (10 mg/kg , i.p., 2 h before i.v. infusion of the tracer) or fluoxetine (10 mg/kg, i.p. 2 h before tracer) did not affect significantly plasma tryptophan concentration in male rats. Desipramine and fluoxetine decreased the rate of 5-HT synthesis in the regions that contain serotonergic cell bodies (i.e. dorsal raphe, median raphe, magnus raphe). These decreases, calculated as percent (%) of the synthesis rate in the control group, were 23, 19 and 28% after desipramine and 17, 18 and 23 % after fluoxetine administration, respectively. Desipramine and fluoxetine increased the rate of 5-HT synthesis in the majority of areas containing serotonergic terminals. The administration of desipramine elevated the rate of 5-HT synthesis in sensory-motor (65%), frontal (21%), auditory (21%), parietal (45%) cortex, caudate (39%), mediate geniculate body (42%), in superior colliculus (26%), and in globus pallidus (31%). The administration of fluoxetine increased the rate of 5-HT synthesis in sensory-motor (32%), visual (35%), auditory (28%) cortex, in caudate (42%), in mediate geniculate body (29%), and in superior colliculus (57%). In some brain regions of the serotonergic terminals and in pineal body desipramine and fluoxetine showed the opposite effects on the 5-HT synthesis rate. The administration of desipramine decreased the rate of 5-HT synthesis in ventral tegmental area (17%), in superior olive (31%), and in pineal body (75%). The administration of fluoxetine increased the 5-HT synthesis rate in ventral tegmental area (23%), in substantia nigra (27%), in inferior colliculus (53%), and in pineal body (41%). These data suggest that the effects of desipramine (noradrenaline uptake inhibitor) and fluoxetine (5-HT uptake inhibitor) on the 5-HT synthesis rate in the rat brain, are regionally dependent. Supported by the MRC of Canada (MT-13368), US Public Service (RO1-NS29629) and Croatian Ministry of Science. Diksic M, Nagahiro S, Sourkes TL, Yamamoto YL. A new method to measure brain serotonin synthesis in vivo. I. Theory and basic data for a biological model. J Cereb. Blood Flow Metab. 10: 1-12, 1990.

Published
2000

89. Acute effect of fluvoxamine on the serotonin synthesis rate in rat brain areas innervated by dorsal and median raphe nuclei: an autoradiographic study

Author

Muck-Šeler, Dorotea, Pivac, Nela, Diksic, Mirko, Mendlewicz, J, and Souery, D.

Subjects
serotonin synthesis rate, rat brain regions, fluvoxamine, autoradiography
Abstract

A considerable body of evidence points to the involvement of neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression. The present study was undertaken to gain further insight into relationship between serotonergic system and the mechanism of action of antidepressants. The acute effect of fluvoxamine (antidepressant, a selective 5-HT reuptake inhibitor), on the 5-HT synthesis rate was investigated in the rat brain regions, using the ŕ-14C-methyl-L-tryptophan (specific activity 55 mCi/mmol) as a tracer in an autoradiograpic method (Diksic et al., 1990). Fluvoxamine (25 mg/kg) and saline (control) were injected intraperitoneally, one hours before injection of tracer (30 ćCi). There were no changes in the concentrations of plasma free tryptophan in fluvoxamine and saline-treated rats. In the areas of serotonergic cell bodies the decrease in 5-HT synthesis rate in fluvoxamine treated rats, calculated as a percent (%) of the synthesis rate in the control group was -32% in magnus and -20% in median raphe nuclei (MRN), while a nonsignificant change in 5-HT synthesis rate was observed in the dorsal raphe nuclei (DRN) (-3%). It the areas of nerve terminals a pronounced increase in synthesis rate was observed in dorsal hippocampus (+41%), region receiving a preferential MRN innervation (Steinbusch, 1981). There were no changes in synthesis rate in median (-12%) and lateral (-23%) part of caudatus-putamen, nucleus accumbens (-4%), VTA (-15%) and frontal cortex (-7%), the areas of nerve terminals reported to receive 5-HT projections mostly from the DRN. In the majority of the rat brain structures receiving mixed DRN/MRN inputs the rate of 5-HT synthesis was significantly increased: sensory-motor (+36%), parietal (+37%), visual (+38%) and auditory (+65%) cortex, medial geniculate body (+48%), substantia nigra pars compacta (+56 %), ventral hippocampus (43%), and superior colliculus (+38%). The decrease in 5-HT synthesis was observed only in the region of medial forebrain bundle (-20%). The preliminary results shown that acute administration of fluvoxamine effects 5-HT synthesis rate in the regionally specific pattern. Supported by the MRC of Canada (MT13368), US Public service (RO1-NS29629) and Croatian Ministry of Science. -Diksic,M., Nagahiro, S., Sourkes, T.L.and Yamamoto, Y.L. A new method to measure brain serotonin synthesis in vivo.I. Theory and basic data for a biological model, J.Cereb. Blood Flow Metab.,10:1-12 (1990). -Steinbusch, H.W.M. Distribution of serotonin-immunoreactivity in the central nervous system of the rat cell bodies and terminals. Neuroscience, 6:557-618, 1981.

Published
2000

90. Acute effect of monoamine oxidase inhibitors on the 5-HT synthesis rate in the rat brain: An autoradiographic study

Author

Muck-Šeler, Dorotea, Diksic, Mirko, and Vitale, Branko

Subjects
clorgyline, 5-HT synthesis rate, autoradiography, rat brain, deprenyl
Abstract

The effect of acute administration of clorgyline ( a selective inhibitor of monoamine oxidase / MAO/ type A) and deprenyl (a selective inhibitor of MAO type B) on the serotonin (5-HT) synthesis rate, was determined in 28 regions of the rat brain using an autoradiographic method and 14C-alpha-methyl-L-tryptophan as a tracer. Results indicated that MAO inhibitors have different effects on the 5-HT synthesis rate in different brain regions. Clorgyline (10 mg/kg) and deprenyl (30 mg/kg) decreased 5-HT synthesis rate in the areas of nerve cell bodies i.e. in dorsal (-18 percent and -20 percent), median (-27 percent and -41 percent) raphe nuclei as well as in pineal body (-31 percent and -71 percent). Clorgyline increased 5-HT synthesis rate in sensory-motor cortex (37 percent), lateral caudate (37 percent) and ventral hippocampus (36 percent). In contrast, deprenyl did not induce significant changes in 5-HT synthesis rate in nerve terminals. Results suggest that the MAO activity participates in the regulation of 5-HT synthesis rate in the areas of cell bodies as well as in the nerve terminals. Research supported in part by the NIH and MRC grants.

Published
1997

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