Psychiatry Research: Neuroimaging
Volume 154, Issue 3 , Pages 241-251 , 15 April 2007

Altered benzodiazepine receptor sensitivity in alcoholism: A study with fMRI and acute lorazepam challenge

  • Ralf G.M. Schlösser

      Affiliations

    • Department of Psychiatry, University of Jena, Philosophenweg 3, 07740 Jena, Germany
    • Corresponding Author InformationCorresponding author. Tel.: +49 3641 35287; fax: +49 3641 35444.
    • ,
  • Thomas Gesierich

      Affiliations

    • Department of Psychiatry, University of Mainz, Germany
    • ,
  • Gerd Wagner

      Affiliations

    • Department of Psychiatry, University of Jena, Philosophenweg 3, 07740 Jena, Germany
    • ,
  • Matthias Bolz

      Affiliations

    • Department of Psychiatry, University of Jena, Philosophenweg 3, 07740 Jena, Germany
    • ,
  • Gerhard Gründer

      Affiliations

    • Department of Psychiatry, University of Mainz, Germany
    • ,
  • Thomas F. Dielentheis

      Affiliations

    • Department of Psychiatry, University of Mainz, Germany
    • ,
  • Claudius Scherb

      Affiliations

    • Department of Psychiatry, University of Mainz, Germany
    • ,
  • Peter Stoeter

      Affiliations

    • Department of Neuroradiology, University of Mainz, Germany

Received 15 May 2004 ,Revised 16 January 2006 ,Accepted 11 February 2006.

References 

  1. Abboud HA. Super Lab. Pro. 1.06. Phoenix: Cedrus; 1998;
  2. Alexander G, DeLong M, Strick P. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience. 1986;9:357–381
  3. Banger M, Philipp M, Herth T, Hebenstreit M, Aldenhoff J. Development of a rating scale for quantitative measurement of the alcohol withdrawal syndrome. European Archives of Psychiatry and Clinical Neuroscience. 1992;241:241–246
  4. Buck KJ, Finn DA. Genetic factors in addiction: QTL mapping and candidate gene studies implicate GABAergic genes in alcohol and barbiturate withdrawal in mice. Addiction. 2001;96:139–149
  5. Cohen J, Forman S, Braver T, Casey B, Servan-Schreiber D, Noll D. Activation of prefrontal cortex in a non-spatial working memory task with functional MRI. Human Brain Mapping. 1994;1:293–304
  6. Coull JT, Middleton HC, Robbins TW, Sahakian BJ. Contrasting effects of clonidine and diazepam on tests of working memory and planning. Psychopharmacology. 1995;120:311–321
  7. Curran HV, Schifano F, Lader M. Models of memory dysfunction? A comparison of the effects of scopolamine and lorazepam on memory, psychomotor performance and mood. Psychopharmacology. 1991;103:83–90
  8. Davis KM, Wu JY. Role of glutamatergic and GABAergic systems in alcoholism. Journal of Biomedical Science. 2001;8:7–19
  9. de Wit H, Metz J, Wagner N, Cooper M. Behavioral and subjective effects of ethanol: relationship to cerebral metabolism using PET. Alcoholism, Clinical and Experimental Research. 1990;14:482–489
  10. de Wit H, Metz J, Wagner N, Cooper M. Effects of diazepam on cerebral metabolism and mood in normal volunteers. Neuropsychopharmacology. 1991;5:33–41
  11. Desmond JE, Chen SH, DeRosa E, Pryor MR, Pfefferbaum A, Sullivan EV. Increased frontocerebellar activation in alcoholics during verbal working memory: an fMRI study. NeuroImage. 2003;19:1510–1520
  12. Duka T, Redemann B, Voet B. Scopolamine and lorazepam exert different patterns of effects in a test battery assessing stages of information processing. Psychopharmacology. 1995;119:315–324
  13. Durstewitz D, Seamans JK, Sejnowski TJ. Dopamine-mediated stabilization of delay-period activity in a network model of prefrontal cortex. Journal of Neurophysiology. 2000;83:1733–1750
  14. Fleishaker JC, Garzone PD, Chambers JH, Sirocco K, Weingartner H. Comparison of the spectrum of cognitive effects of alprazolam and adinazolam after single doses in healthy subjects. Psychopharmacology. 1995;120:169–176
  15. Freund RK, van Horne CG, Harlan T, Palmer MR. Electrophysiological interactions of ethanol with GABAergic mechanisms in the rat cerebellum in vivo. Alcoholism, Clinical and Experimental Research. 1993;17:321–328
  16. Friston K, Ashburner J, Frith C, Poline J, Heather J, Frackowiak R. Spatial registration and normalization of images. Human Brain Mapping. 1995;2:165–189
  17. Friston KJ, Holmes AP, Poline JB, Grasby PJ, Williams SC, Frackowiak RS, et al. Analysis of fMRI time-series revisited. NeuroImage. 1995;2:45–53
  18. Friston KJ, Holmes AP, Worsley KJ, Poline J-B, Frith CD, Frackowiak RSJ. Statistical parametric maps in functional imaging: a general linear approach. Human Brain Mapping. 1995;2:189–280
  19. Fuster JM. The Prefrontal Cortex. Philadelphia: Lippincott-Raven; 1997;
  20. Grobin AC, Fritschy JM, Morrow AL. Chronic ethanol administration alters immunoreactivity for GABAA receptor subunits in rat cortex in a region-specific manner. Alcoholism, Clinical and Experimental Research. 2000;24:1137–1144
  21. Grobin AC, Papadeas ST, Morrow AL. Regional variations in the effects of chronic ethanol administration on GABAA receptor expression: potential mechanisms. Neurochemistry International. 2000;37:453–461
  22. Gur RC, Erwin RJ, Gur RE. Neurobehavioral probes for physiologic neuroimaging studies. Archives of General Psychiatry. 1992;49:409–414
  23. Hood HM, Buck KJ. Allelic variation in the GABA A receptor gamma2 subunit is associated with genetic susceptibility to ethanol-induced motor incoordination and hypothermia, conditioned taste aversion, and withdrawal in BXD/Ty recombinant inbred mice. Alcoholism, Clinical and Experimental Research. 2000;24:1327–1334
  24. Jonides J, Schumacher E, Smith E, Lauber E, Awh E, Minoshima S, et al. Verbal working memory load affects regional brain activation as measured by PET. Journal of Cognitive Neuroscience. 1997;9:462–475
  25. June HL, Harvey SC, Foster KL, McKay PF, Cummings R, Garcia M, et al. GABAA receptors containing α5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors: an extended ethanol reward circuitry. Journal of Neuroscience. 2001;21:2166–2177
  26. Keverne EB. GABA-ergic neurons and the neurobiology of schizophrenia and other psychoses. Brain Research Bulletin. 1999;48:467–473
  27. Korpi ER. Role of GABAA receptors in the actions of alcohol and in alcoholism: recent advances. Alcohol and Alcoholism. 1994;29:115–129
  28. Korpi ER, Kleingoor C, Kettenmann H, Seeburg PH. Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor. Nature. 1993;361:356–359
  29. Lachner G, Wittchen HU, Perkonigg A, Holly A, Schuster P, Wunderlich U, et al. Structure, content and reliability of the Munich-Composite International Diagnostic Interview (M-CIDI) substance use sections. European Addiction Research. 1998;4:28–41
  30. Lewis DA. GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia. Brain Research Reviews. 2000;31:270–276
  31. 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
  32. Mellers JD, Bullmore E, Brammer M, Williams SC, Andrew C, Sachs N, et al. Neural correlates of working memory in a visual letter monitoring task: an fMRI study. NeuroReport. 1995;7:109–112
  33. Mihalek RM, Bowers BJ, Wehner JM, Kralic JE, VanDoren MJ, Morrow AL, et al. GABAA-receptor delta subunit knockout mice have multiple defects in behavioral responses to ethanol. Alcoholism, Clinical and Experimental Research. 2001;25:1708–1718
  34. Myrick H, Brady KT, Malcolm R. New developments in the pharmacotherapy of alcohol dependence. American Journal on Addictions. 2001;10:3–15
  35. Nelson RM, Green AR, Lambert DG, Hainsworth AH. On the regulation of ischaemia-induced glutamate efflux from rat cortex by GABA; in vitro studies with GABA, clomethiazole and pentobarbitone. British Journal of Pharmacology. 2000;130:1124–1130
  36. Nichols JM, Martin F, Kirkby KC. A comparison of the effect of lorazepam on memory in heavy and low social drinkers. Psychopharmacology. 1993;112:475–482
  37. Owen AM, Stern CE, Look RB, Tracey I, Rosen BR, Petrides M. Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex. Proceedings of the National Academy of Sciences of the United States of America. 1998;95:7721–7726
  38. Papadeas S, Grobin AC, Morrow AL. Chronic ethanol consumption differentially alters GABAA receptor alpha1 and alpha4 subunit peptide expression and GABAA receptor-mediated 36 Cl(−) uptake in mesocorticolimbic regions of rat brain. Alcoholism, Clinical and Experimental Research. 2001;25:1270–1275
  39. Petrie J, Sapp DW, Tyndale RF, Park MK, Fanselow M, Olsen RW. Altered GABA-A receptor subunit and splice variant expression in rats treated with chronic intermittent ethanol. Alcoholism, Clinical and Experimental Research. 2001;25:819–828
  40. Pfefferbaum A, Desmond JE, Galloway C, Menon V, Glover GH, Sullivan EV. Reorganization of frontal systems used by alcoholics for spatial working memory: an fMRI study. NeuroImage. 2001;14:7–20
  41. Rao SG, Williams GV, Goldman-Rakic PS. Destruction and creation of spatial tuning by disinhibition: GABAA blockade of prefrontal cortical neurons engaged by working memory. Journal of Neuroscience. 2000;20:485–494
  42. Rassnick S, D'Amico E, Riley E, Koob GF. GABA antagonist and benzodiazepine partial inverse agonist reduce motivated responding for ethanol. Alcoholism, Clinical and Experimental Research. 1993;17:124–130
  43. Rassnick S, Krechman J, Koob GF. Chronic ethanol produces a decreased sensitivity to the response— disruptive effects of GABA receptor complex antagonists. Pharmacology, Biochemistry and Behavior. 1993;44:943–950
  44. Rassnick S, D'Amico E, Riley E, Pulvirenti L, Zieglgansberger W, Koob GF. GABA and nucleus accumbens glutamate neurotransmission modulate ethanol self-administration in rats. Annals of the New York Academy of Sciences. 1992;654:502–505
  45. Rusted JM, Eaton-Williams P, Warburton DM. A comparison of the effects of scopolamine and diazepam on working memory. Psychopharmacology. 1991;105:442–445
  46. Schlösser R, Gesierich T, Kaufmann B, Vucurevic G, Hunsche S, Gawehn J, et al. Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling. NeuroImage. 2003;19:751–763
  47. Schlösser R, Gesierich T, Kaufmann B, Vucurevic G, Stoeter P. Altered effective connectivity in drug free schizophrenic patients. NeuroReport. 2003;14:2233–2237
  48. Schmahmann JD, Pandya DN. The cerebrocerebellar system. International Review of Neurobiology. 1997;41:31–60
  49. Smith MA, Jewkes DA. Chlormethiazole. In:  Levy RH,  Mattson RH,  Meldrum BS editor. Antiepileptic Drugs. New York: Raven Press; 1995;
  50. Stolerman IP, Olufsen K. Generalisation of ethanol with drug mixtures containing a positive modulator of the GABAA receptor and an NMDA antagonist. Neuropharmacology. 2001;40:123–130
  51. Streeter CC, Ciraulo DA, Harris GJ, Kaufman MJ, Lewis RF, Knapp CM, et al. Functional magnetic resonance imaging of alprazolam-induced changes in humans with familial alcoholism. Psychiatry Research. Neuroimaging. 1998;82:69–82
  52. Stromberg MF, Mackler SA, Volpicelli JR, O'Brien CP, Dewey SL. The effect of gamma-vinyl-GABA on the consumption of concurrently available oral cocaine and ethanol in the rat. Pharmacology, Biochemistry and Behavior. 2001;68:291–299
  53. Sullivan EV. Compromised pontocerebellar and cerebellothalamocortical systems: speculations on their contributions to cognitive and motor impairment in nonamnesic alcoholism. Alcoholism, Clinical and Experimental Research. 2003;27:1409–1419
  54. Sullivan EV, Harding AJ, Pentney R, Dlugos C, Martin PR, Parks MH, et al. Disruption of frontocerebellar circuitry and function in alcoholism. Alcoholism, Clinical and Experimental Research. 2003;27:301–309
  55. Tapert SF, Brown GG, Kindermann SS, Cheung EH, Frank LR, Brown SA. fMRI measurement of brain dysfunction in alcohol-dependent young women. Alcoholism, Clinical and Experimental Research. 2001;25:236–245
  56. Vaucher E, Tong XK, Cholet N, Lantin S, Hamel E. GABA neurons provide a rich input to microvessels but not nitric oxide neurons in the rat cerebral cortex: a means for direct regulation of local cerebral blood flow. Journal of Comparative Neurology. 2000;421:161–171
  57. Vekovischeva OY, Haapalinna A, Sarviharju M, Honkanen A, Korpi ER. Cerebellar GABAA receptors and anxiolytic action of diazepam. Brain Research. 1999;837:184–187
  58. Volkow ND, Hitzemann R, Wolf AP, Logan J, Fowler JS, Christman D, et al. Acute effects of ethanol on regional brain glucose metabolism and transport. Psychiatry Research. 1990;35:39–48
  59. Volkow ND, Wang GJ, Begleiter H, Hitzemann R, Pappas N, Burr G, et al. Regional brain metabolic response to lorazepam in subjects at risk for alcoholism. Alcoholism, Clinical and Experimental Research. 1995;19:510–516
  60. Volkow ND, Wang GJ, Hitzemann R, Fowler JS, Wolf AP, Pappas N, et al. Decreased cerebral response to inhibitory neurotransmission in alcoholics. American Journal of Psychiatry. 1993;150:417–422
  61. Volkow ND, Wang GJ, Overall JE, Hitzemann R, Fowler JS, Pappas N, et al. Regional brain metabolic response to lorazepam in alcoholics during early and late alcohol detoxification. Alcoholism, Clinical and Experimental Research. 1997;21:1278–1284
  62. Wagemans J, Notebaert W, Boucart M. Lorazepam but not diazepam impairs identification of pictures on the basis of specific contour fragments. Psychopharmacology. 1998;138:326–333
  63. Wang GJ, Volkow ND, Franceschi D, Fowler JS, Thanos PK, Scherbaum N, et al. Regional brain metabolism during alcohol intoxication. Alcoholism, Clinical and Experimental Research. 2000;24:822–829
  64. Wittchen, H.-U., Beloch, E., Garcynski, E., Holly, A., Lachner, G., Perkonigg, A., Pfütze, E.-M., Schuster, P., Vodermaier, A., Vossen, A., Wunderlich, U., Zieglgänsberger, S., 1995. Munich Composite International Diagnostic Interview (M-CIDI, Paper-pencil 2.2, 2/95), Max-Planck-Institute for Psychiatry, Clinical Institute, Munich.

PII: S0925-4927(06)00151-X

doi: 10.1016/j.pscychresns.2006.02.008

Psychiatry Research: Neuroimaging
Volume 154, Issue 3 , Pages 241-251 , 15 April 2007

Article Tools

* Image Usage & Resolution