Psychiatry Research: Neuroimaging
Volume 174, Issue 2 , Pages 130-137 , 30 November 2009

The effects of lorazepam on extrastriatal dopamine D2/3-receptors—A double-blind randomized placebo-controlled PET study

  • Harry Vilkman

      Affiliations

    • Turku PET Centre, University of Turku, Turku, Finland
  • ,
  • Jaana Kajander

      Affiliations

    • Turku PET Centre, University of Turku, Turku, Finland
  • ,
  • Sargo Aalto

      Affiliations

    • Turku PET Centre, University of Turku, Turku, Finland
    • Department of Psychology, Åbo Akademi University, Turku, Finland
  • ,
  • Tero Vahlberg

      Affiliations

    • Institute of Clinical Medicine, Biostatistics, University of Turku, Turku, Finland
  • ,
  • Kjell Någren

      Affiliations

    • Turku PET Centre, Radiopharmaceutical Chemistry Laboratory, Turku, Finland
  • ,
  • Topias Allonen

      Affiliations

    • Turku PET Centre, University of Turku, Turku, Finland
  • ,
  • Erkka Syvälahti

      Affiliations

    • Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland
  • ,
  • Jarmo Hietala

      Affiliations

    • Turku PET Centre, University of Turku, Turku, Finland
    • Department of Psychiatry, University of Turku, Kunnallissairaalantie 20, Building 9, 20700 Turku, Finland
    • Corresponding Author InformationCorresponding author. Department of Psychiatry, University of Turku, Kunnallissairaalantie 20, Building 9, 20700 Turku, Finland. Tel.: +358 2 269 2520; fax: +358 2 269 2528.

Received 6 December 2007 ,Revised 19 April 2009 ,Accepted 19 April 2009.

References 

  1. Aalto S, Ihalainen J, Hirvonen J, Kajander J, Scheinin H, Tanila H, et al. Cortical glutamate-dopamine interaction and ketamine-induced psychotic symptoms in man. Psychopharmacology. 2005;182:375–383
  2. Aalto S, Brück A, Laine M, Någren K, Rinne JO. Frontal and temporal dopamine release during working memory and attention tasks in healthy humans: a positron emission tomography study using the high-affinity dopamine D2 receptor ligand [11C]FLB 457. Journal of Neuroscience. 2005;25:2471–2477
  3. Aalto S, Hirvonen J, Kaasinen V, Hagelberg N, Kajander J, Någren K, et al. The effects of d-amphetamine on extrastriatal dopamine D(2)/D(3) receptors: a randomized, double-blind, placebo controlled PET study with [(11)C]FLB 457 in healthy subjects. European Journal of Nuclear Medicine and Molecular Imaging. 2009;36:475–483
  4. Aquilonius S-M, Eckernäs S-Å. A Colour Atlas of the Human Brain. Stockholm, Sweden: Esselte studium; 1980;
  5. Bentué-Ferrer D, Reymann JM, Tribut O, Allain H, Vasar E, Bourin M. Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam. European Neuropsychopharmacology. 2001;11:41–50
  6. Biggio G, Concas A, Corda MG, Giorgi O, Sanna E, Serra M. GABAergic and dopaminergic transmission in the rat cerebral cortex: effect of stress, anxiolytic and anxiogenic drugs. Pharmacology & Therapeutics. 1990;48:121–142
  7. Blomqvist G. On the construction of functional maps in positron emission tomography. Journal of Cerebral Blood Flow and Metabolism. 1984;4:629–632
  8. Brose N, O'Neill RD, Boutelle MG, Fillenz M. Dopamine in the basal ganglia and benzodiazepine-induced sedation. Neuropharmacology. 1988;27:589–595
  9. Bunney BS, Aghajanian GK. Dopaminergic influence in the basal ganglia: evidence for striatonigral feedback regulation. Research Publications – Association for Research in Nervous and Mental Disease. 1976;55:249–267
  10. Busatto GF, Pilowsky LS, Costa DC, Ell PJ, David AS, Lucey JV, et al. Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia. American Journal of Psychiatry. 1997;154:56–63
  11. Chou YH, Karlsson P, Halldin C, Olsson H, Farde L. A PET study of D(1)-like dopamine receptor ligand binding during altered endogenous dopamine levels in the primate brain. Psychopharmacology. 1999;146:220–227
  12. Chou YH, Halldin C, Farde L. Effect of amphetamine on extrastriatal D2 dopamine receptor binding in the primate brain: a PET study. Synapse. 2000;38:138–143
  13. Chugani DC, Ackermann RF, Phelps ME. In vivo [3H]Spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization. Journal of Cerebral Blood Flow and Metabolism. 1988;8:291–303
  14. Dazzi L, Motzo C, Imperato A, Serra M, Gessa GL, Biggio G. Modulation of basal and stress-induced release of acetylcholine and dopamine in rat brain by abecarnil and imidazenil, two anxioselective gamma-aminobutyric acid-A receptor modulators. Journal of Pharmacology and Experimental Therapeutics. 1995;273:241–247
  15. Del Arco A, Mora F. Prefrontal cortex–nucleus accumbens interaction: in vivo modulation by dopamine and glutamate in the prefrontal cortex. Pharmacology, Biochemistry and Behavior. 2008;90:226–235
  16. Dewey SL, Smith GS, Logan J, Brodie JD, Yu DW, Ferrieri RA, et al. GABAergic inhibition of endogenous dopamine release measured in vivo with 11C-raclopride and positron emission tomography. Journal of Neuroscience. 1992;12:3773–3780
  17. Di Chiara G, Porceddu ML, Vargiu L, Argiolas A, Gessa GL. Evidence for dopamine receptors mediating sedation in the mouse brain. Nature. 1976;264:564–567
  18. Farde L, Suhara T, Nyberg S, Karlsson P, Nakashima Y, Hietala J, et al. A PET-study of [C-11]FLB 457 binding to extrastriatal D-2-dopamine receptors in healthy subjects and antipsychotic drug-treated patients. Psychopharmacology. 1997;133:396–404
  19. Feenstra MGP, Bottenblom MHA, van Uum JFM. Novelty-induced increase in dopamine in the rat prefrontal cortex in vivo: inhibition by diazepam. Neuroscience Letters. 1995;189:81–84
  20. Finlay JM, Zigmond MJ, Abercrombie ED. Increased dopamine and norepinephrine release in medial prefrontal cortex induced by acute and chronic stress: effects of diazepam. Neuroscience. 1995;64:619–628
  21. Frankle WG, Laruelle M, Haber SN. Prefrontal cortical projections to the midbrain in primates: evidence for a sparse connection. Neuropsychopharmacology. 2006;31:1627–1636
  22. Friston KJ, Holmes AP, Worsley KJ, Poline JP, Frith CD, Frackowiak RS. Statistical parametric maps in functional imaging: a general linear approach. Human Brain Mapping. 1995;2:189–210
  23. Fujita M, Verhoeff NPLG, Varrone A, Zoghbi SS, Baldwin RM, Jatlow PA, et al. Imaging extrastriatal dopamine D(2) receptor occupancy by endogenous dopamine in healthy humans. European Journal of Pharmacology. 2000;387:179–188
  24. Gifkins A, Greba Q, Kokkinidis L. Ventral tegmental area dopamine neurons mediate the shock sensitization of acoustic startle: a potential site of action for benzodiazepine anxiolytics. Behavioral Neuroscience. 2002;116:785–794
  25. Gottesmann C. The neurochemistry of waking and sleeping mental activity: the disinhibition dopamine hypothesis. Psychiatry and Clinical Neurosciences. 2002;56:345–354
  26. Greenblatt DJ. Clinical pharmacokinetics of oxazepam and lorazepam. Clinical Pharmacokinetics. 1981;6:89–105
  27. Greenblatt DJ, Shader RI, Franke K, MacLaughlin DS, Harmatz JS, Allen MD, et al. Pharmacokinetics and bioavailability of intravenous, intramuscular and oral lorazepam in humans. Journal of Pharmaceutical Sciences. 1979;68:57–63
  28. Gunn RN, Lammertsma AA, Hume SP, Cunningham VJ. Parametric imaging of ligand–receptor binding in PET using a simplified reference region model. NeuroImage. 1997;6:279–287
  29. Hagelberg N, Aalto S, Kajander J, Oikonen V, Hinkka S, Någren K, et al. Alfentanil increases dopamine D2/D3 receptor binding in healthy subjects. Pain. 2004;109:86–93
  30. Halldin C, Farde L, Högberg T, Mohell N, Hall H, Suhara T, et al. Carbon-11-FLB 457: a radioligand for extrastriatal D2 dopamine receptors. Journal of Nuclear Medicine. 1995;36:1275–1281
  31. Hegarty AA, Vogel WH. The effect of acute and chronic diazepam treatment on stress-induced changes in cortical dopamine in the rat. Pharmacology, Biochemistry, and Behavior. 1995;52:771–778
  32. Hietala J, Kuoppamäki M, Någren K, Lehikoinen P, Syvälahti E. Effects of lorazepam administration on striatal dopamine D2 receptor binding characteristics in man – a positron emission tomography study. Psychopharmacology. 1997;132:361–365
  33. Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversible binding radioligands. Journal of Cerebral Blood Flow and Metabolism. 2007;27:1533–1539
  34. Joel D, Weiner I. The connections of the dopaminergic system with the striatum in rats and primates: an analysis with respect to the functional and compartmental organization of the striatum. Neuroscience. 2000;96:451–474
  35. Kalivas PW. Neurotransmitter regulation of dopamine neurons in the ventral tegmental area. Brain Research. Brain Research Reviews. 1993;18:75–113
  36. Kubota Y, Inagaki S, Kito S, Wu JY. Dopaminergic axons directly make synapses with GABAergic neurons in the rat neostriatum. Brain Research. 1987;406:147–156
  37. Lammertsma AA, Hume SP. Simplified reference tissue model for PET receptor studies. NeuroImage. 1996;4:153–158
  38. Laruelle M. Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. Journal of Cerebral Blood Flow and Metabolism. 2000;20:423–451
  39. Lawson CL, Hanson RJ. Solving Least Squares Problems. New Jersey: Prentice-Hall; 1974;
  40. Levy F. Pharmacological and therapeutic directions in ADHD: specificity in the PFC. Behavioral and Brain Functions. 2008;4:12;(e-pub)
  41. Lokwan SJ, Overton PG, Berry MS, Clark D. The medial prefrontal cortex plays an important role in the excitation of A10 dopaminergic neurons following intravenous muscimol administration. Neuroscience. 2000;95:647–656
  42. Lorr M, Wunderlich RA. A semantic differential mood scale. Journal of Clinical Psychology. 1988;44:33–36
  43. Lorr M, McNair DM, Fisher SU. Evidence for bipolar mood states. Journal of Personality Assessment. 1982;46:432–436
  44. Lynd-Balta E, Haber SN. The organization of midbrain projections to the striatum in the primate: sensorimotor-related striatum versus ventral striatum. Neuroscience. 1994;59:625–640
  45. Maj J, Przewlocka B, Kukulka L. Sedative action of low doses of dopaminergic agents. Polish Journal of Pharmacology and Pharmacy. 1977;29:11–21
  46. Malizia AL, Cunningham VJ, Bell CJ, Liddle PF, Jones T, Nutt DJ. Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder: preliminary results from a quantitative PET study. Archives of General Psychiatry. 1998;55:715–720
  47. Matthew E, Andreason P, Pettigrew K, Carson RE, Herscovitch P, Cohen R, et al. Benzodiazepine receptors mediate regional blood flow changes in the living human brain. Proceedings of the National Academy of Sciences of the United States of America. 1995;92:2775–2779
  48. McRitchie DA, Cartwright H, Pond SM, van der Schyf CJ, Castagnoli N, van der Nest DG, et al. The midbrain dopaminergic cell groups in the baboon Papio ursinus. Brain Research Bulletin. 1998;47:611–623
  49. Mehta AK, Ticku MK. An update on GABA-A receptors. Brain Research. Brain Research Reviews. 1999;29:196–217
  50. Montgomery AJ, Asselin MC, Farde L, Grasby PM. Measurement of methylphenidate-induced change in extrastriatal dopamine concentration using [11C]FLB 457 PET. Journal of Cerebral Blood Flow and Metabolism. 2007;27:369–377
  51. O'Brien DP, White FJ. Inhibition of non-dopamine cells in the ventral tegmental area by benzodiazepines: relationship to A10 dopamine cell activity. European Journal of Pharmacology. 1987;142:343–354
  52. O'Dowd BF, Ji X, Alijaniaram M, Rajaram RD, Kong MM, Rashid A, et al. Dopamine receptor oligomerization visualized in living cells. Journal of Biological Chemistry. 2005;280:37225–37235
  53. Olsson H, Halldin C, Swahn CG, Farde L. Quantification of [11C]FLB 457 binding to extrastriatal dopamine receptors in the human brain. Journal of Cerebral Blood Flow and Metabolism. 1999;19:1164–1173
  54. Rimondini R, Fuxe K, Ferre S. Multiple intramembrane receptor–receptor interactions in the regulation of striatal dopamine D2 receptors. NeuroReport. 1999;10:2051–2054
  55. Sareen J, Campbell DW, Leslie WD, Malisza KL, Stein MB, Paulus MP, et al. Striatal function in generalized social phobia: a functional magnetic resonance imaging study. Biological Psychiatry. 2007;61:396–404
  56. Schneier FR, Liebowitz MR, Abi-Dargham A, Zea-Ponce Y, Lin S-H, Laruelle M. Low dopamine D2 receptor binding potential in social phobia. American Journal of Psychiatry. 2000;157:457–459
  57. Seeman P, Schwarz J, Chen JF, Szechtman H, Perreault M, McKnight GS, et al. Psychosis pathways converge via D2 high dopamine receptors. Synapse. 2006;60:319–346
  58. Slifstein M, Laruelle M. Models and methods for derivation of in vivo neuroreceptor parameters with PET and SPECT reversible radiotracers. Nuclear Medicine and Biology. 2001;28:595–608
  59. Tiihonen J, Kuikka J, Bergström K, Lepola U, Koponen H, Leinonen E. Dopamine reuptake site densities in patients with social phobia. American Journal of Psychiatry. 1997;154:239–242
  60. Tiihonen J, Kuikka J, Räsänen P, Lepola U, Koponen H, Liuska A, et al. Cerebral bezodiazepine receptor binding and distribution in generalized anxiety disorder: a fractal analysis. Molecular Psychiatry. 1997;2:463–471
  61. Tsukada H, Nishiyama S, Fukumoto D, Sato K, Kakiuchi T, Domino EF. Chronic NMDA antagonism impairs working memory, decreases extracellular dopamine, and increases D1 receptor binding in prefrontal cortex of conscious monkeys. Neuropsychopharmacology. 2005;30:1861–1869
  62. van Kammen DP. Gamma-aminobutyric acid (GABA) and the dopamine hypothesis of schizophrenia. American Journal of Psychiatry. 1977;134:138–143
  63. Vilkman H, Kajander J, Någren K, Oikonen V, Syvälahti E, Hietala J. Measurement of extrastriatal D2-like receptor binding with [11C] FLB 457 – a test–retest analysis. European Journal of Nuclear Medicine. 2000;27:1666–1673
  64. Vivo M, Lin H, Strange PG. Investigation of cooperativity in the binding of ligands to the D(2) dopamine receptor. Molecular Pharmacology. 2006;69:226–235
  65. Volkow ND, Wang GJ, Hitzemann R, Fowler JS, Pappas N, Lowrimore P, et al. Depression of thalamic metabolism by lorazepam is associated with sleepiness. Neuropsychopharmacology. 1995;12:123–132
  66. Wang GJ, Volkow ND, Overall J, Hitzemann RJ, Pappas N, Pascani K, et al. Reproducibility of regional brain metabolic responses to lorazepam. Journal of Nuclear Medicine. 1996;37:1609–1613
  67. Wang GJ, Volkow ND, Fowler JS, Hitzemann RJ, Pappas NR, Netusil N. Evaluation of gender difference in regional brain metabolic responses to lorazepam. Psychiatry Research. 1998;82:37–46
  68. Waszczak BL, Walters JR. Effects of GABAergic drugs on single unit activity of A9 and A10 dopamine neurons. Brain Research Bulletin. 1980;5(suppl. 2):465–470
  69. Waszczak BL, Walters JR. Intravenous GABA agonist administration stimulates firing of A10 dopaminergic neurons. European Journal of Pharmacology. 1980;66:141–144
  70. Zhou Y, Brasic JR, Ye W, Dogan AS, Hilton J, Singer HS, et al. Quantification of cerebral serotonin binding in normal controls and subjects with Tourette's syndrome using [11C]MDL 100,907 and (+)[11C]McN 5652 dynamic PET with parametric imaging approach. NeuroImage. 2004;22(suppl. 2):T98–T99

 The data were presented in abstract form in the 19th ECNP Congress, Paris, France, 16-20 September 2006 (European Neuropsychopharmacology, Volume 16, Supplement 4, page S266).

PII: S0925-4927(09)00110-3

doi: 10.1016/j.pscychresns.2009.04.006

Psychiatry Research: Neuroimaging
Volume 174, Issue 2 , Pages 130-137 , 30 November 2009