Psychiatrie und Psychotherapie

, Volume 3, Issue 2, pp 45–49 | Cite as

Alkoholbedingte Störungen – ein kleines Alphabet der Neurobiologie

  • Jakob Hein
  • Michael Rapp
  • Andreas Heinz
Übersicht
  • 48 Downloads

Zusammenfassung

Die neurobiologische Forschung auf dem Gebiet alkoholbedingter Störungen hat in den letzten Jahren vielfältige wichtige Erkenntnisse erbracht, über die hier eine kurze Übersicht gegeben werden soll. Insbesondere haben sich neue Erkenntnisse auf dem Gebiet der genetischen Disposition dieser Störungen ergeben, aber auch bei der Erforschung der Neurotransmittersysteme konnten mit Hilfe tierexperimentieller Studien und Untersuchungsmethoden der Bildgebung neue Erkenntnisse gewonnen werden. Besonders Forschungsergebnisse zum hypothalamischen-hyophysiär Regelsystem, sowie Rezeptoren für Endocannabinoide und Opiate bieten neue, interessante Aspekte. Aus diesen neurobiologischen Erkenntnissen ergeben sich neue pharmakologische Behandlungsmöglichkeiten zur Behandlung alkoholbedingter Störungen.

Schlüsselwörter

Acamprosat ADH ALDH Alkoholabhängigkeit Cannabinoid-Rezeptoren Dopamin GABA Glutamat HHNNR-Regelachse Ketamin Naltrexon Opiat-Rezeptoren Serotonin 

Neurobiology's little alphabet of alcohol use disorders

Summary

Neurobiological research has yielded a variety of important results on the field of alcohol use disorders in recent years. This article tries to give a brief overview of these results. Especially in researching the genetic disposition many new results have come forward. But also on the field of neurotransmitter changes new findings using animal models as well as modern imaging methods were made. New and interesting insights come from research of the hypothalamic-pituitary gland hormonal systems, endocannabinoid receptors, as well as opiate receptors. New pharmacological approaches for the treatment of alcohol use disorders begin to evolve from these neurobiological findings.

Keywords

Acamprosate ADH ALDH Alcohol dependence Cannabinoid-receptors Dopamine GABA Glutamate HPA-axis Ketamine Naltrexone Opiate-receptors Serotonin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

LITERATUR

  1. Abi-Dargham A, Krystal JH, Anjilvel S, Scanley BE, Zoghbi S, Baldwin RM et al (1998) Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [I-123]iomazenil. Am J Psychiatry 155: 1550–1555PubMedGoogle Scholar
  2. Basavarajappa BS, Hungund BL (2005) Role of the endocannabinoid system in the development of tolerance to alcohol. Alcohol Alcohol 40: 15–24PubMedGoogle Scholar
  3. Bell SM, Reynolds JG, Thiele TE, Gan J, Figlewicz DP, Woods SC (1998) Effects of third intracerebroventricular injections of corticotropin-releasing factor (CRF) on ethanol drinking and food intake. Psychopharmacology 139: 128–135PubMedCrossRefGoogle Scholar
  4. Berridge KC, Robinson TE (1998) What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev 28: 309–369PubMedCrossRefGoogle Scholar
  5. Cheng AT, Gau SF, Chen TH, Chang JC, Chang YT (2004) A 4-year longitudinal study on risk factors for alcoholism. Arch Gen Psychiatry 61: 184–191PubMedCrossRefGoogle Scholar
  6. Crabb DW, Matsumoto M, Chang D, You M (2004) Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proc Nutr Soc 63: 49–63PubMedCrossRefGoogle Scholar
  7. de Vries TJ, Schoffelmeer AN (2005) Cannabinoid CB1 receptors control conditioned drug seeking. Trends Pharmacol Sci 26: 420–426PubMedCrossRefGoogle Scholar
  8. Doudet D, Hommer D, Higley JD, Andreason PJ, Moneman R, Suomi SJ et al (1995) Cerebral glucose metabolism, CSF 5-HIAA levels, and aggressive behavior in rhesus monkeys. Am J Psychiatry 152: 1782–1787PubMedGoogle Scholar
  9. Ehlers CL, Chaplin RI, Wall TL, Lumeng L, Li TK, Owens MJ et al (1992) Corticotropin Releasing-Factor (Crf) – Studies in Alcohol Preferring and Nonpreferring Rats. Psychopharmacology 106: 359–364PubMedCrossRefGoogle Scholar
  10. Ehlers CL, Spence JP, Wall TL, Gilder DA, Carr LG (2004) Association of ALDH1 promoter polymorphisms with alcohol-related phenotypes in southwest California Indians. Alcohol Clin Exp Res 28: 1481–1486PubMedCrossRefGoogle Scholar
  11. Engberg G, Hajos M (1992) Alcohol withdrawal reaction as a result of adaptive changes of excitatory amino acid receptors. Naunyn Schmiedebergs Arch Pharmacol 346: 437–441PubMedCrossRefGoogle Scholar
  12. Gallate JE, McGregor IS (1999) The motivation for beer in rats: effects of ritanserin, naloxone and SR 141716. Psychopharmacology 142: 302–308PubMedCrossRefGoogle Scholar
  13. George MS, Anton RF, Bloomer C, Teneback C, Drobes DJ, Lorberbaum JP et al (2001) Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues. Arch Gen Psychiatry 58: 345–352PubMedCrossRefGoogle Scholar
  14. Giuffrida A, Parsons LH, Kerr TM, Rodriguez d F, Navarro M, Piomelli D (1999) Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 2: 358–363PubMedCrossRefGoogle Scholar
  15. Harada S, Agarwal DP, Goedde HW, Tagaki S, Ishikawa B (1982) Possible protective role against alcoholism for aldehyde dehydrogenase isozyme deficiency in Japan. Lancet 2: 827PubMedCrossRefGoogle Scholar
  16. Heinz A, Higley JD, Gorey JG, Saunders RC, Jones DW, Hommer D et al (1998) In vivo association between alcohol intoxication, aggression, and serotonin transporter availability in nonhuman primates. Am J Psychiatry 155: 1023–1028PubMedGoogle Scholar
  17. Heinz A, Jones DW, Gorey JG, Bennet A, Suomi SJ, Weinberger DR et al (2003a) Serotonin transporter availability correlates with alcohol intake in non-human primates. Mol Psychiatry 8: 231–234CrossRefGoogle Scholar
  18. Heinz A, Lober S, Georgi A, Wrase J, Hermann D, Rey ER et al (2003b) Reward craving and withdrawal relief craving: assessment of different motivational pathways to alcohol intake. Alcohol Alcohol 38: 35–39Google Scholar
  19. Heinz A, Reimold M, Wrase J, Hermann D, Croissant B, Mundle G et al (2005) Correlation of stable elevations in striatal {micro}-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil. Arch Gen Psychiatry 62: 57–64PubMedCrossRefGoogle Scholar
  20. Heinz A, Rommelspacher H, Graf KJ, Kurten I, Otto M, Baumgartner A (1995) Hypothalamic-Pituitary-Gonadal Axis, Prolactin, and Cortisol in alcoholics during withdrawal and after 3 weeks of abstinence – comparison with healthy control subjects. Psychiatry Res 56: 81–95PubMedCrossRefGoogle Scholar
  21. Heinz A, Siessmeier T, Wrase J, Hermann D, Klein S, Grusser SM et al (2004) Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. Am J Psychiatry 161: 1783–1789PubMedCrossRefGoogle Scholar
  22. Higuchi S, Matsushita S, Kashima H (2006) New findings on the genetic influences on alcohol use and dependence. Curr Opin Psychiatry 19: 253–265PubMedCrossRefGoogle Scholar
  23. Higuchi S, Matsushita S, Masaki T, Yokoyama A, Kimura M, Suzuki G et al (2004) Influence of genetic variations of ethanol-metabolizing enzymes on phenotypes of alcohol-related disorders. Ann N Y Acad Sci 1025: 472–480PubMedCrossRefGoogle Scholar
  24. Hillemacher T, Bayerlein K, Reulbach U, Sperling W, Wilhelm J, Mugele B et al (2005) Influence of beer, wine and spirits consumption on craving. Addict Biol 10: 181–186PubMedCrossRefGoogle Scholar
  25. Hillemacher T, Bayerlein K, Wilhelm J, Poleo D, Frieling H, Ziegenbein M et al (2006) Volume intake and craving in alcohol withdrawal. Alcohol Alcohol 41: 61–65PubMedGoogle Scholar
  26. Hungund BL, Szakall I, Adam A, Basavarajappa BS, Vadasz C (2003) Cannabinoid CB1 receptor knockout mice exhibit markedly reduced voluntary alcohol consumption and lack alcohol-induced dopamine release in the nucleus accumbens. J Neurochem 84: 698–704PubMedCrossRefGoogle Scholar
  27. Junghanns K, Backhaus J, Tietz U, Lange W, Bernzen J, Wetterling T et al (2003) Impaired serum cortisol stress response is a predictor of early relapse. Alcohol Alcohol 38: 189–193PubMedGoogle Scholar
  28. Kiefer F, Jahn H, Tarnaske T, Helwig H, Briken P, Holzbach R et al (2003) Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry 60: 92–99PubMedCrossRefGoogle Scholar
  29. Kiefer F, Wiedemann K (2004) Neuroendocrine pathways of addictive behaviour. Addict Biol 9: 205–212PubMedCrossRefGoogle Scholar
  30. Krystal JH, Cramer JA, Krol WF, Kirk GF, Rosenheck RA (2001) Naltrexone in the treatment of alcohol dependence. N Engl J Med 345: 1734–1739PubMedCrossRefGoogle Scholar
  31. Krystal JH, Petrakis IL, Limoncelli D, Webb E, Gueorgueva R, D'Souza DC et al (2003) Altered NMDA glutamate receptor antagonist response in recovering ethanol-dependent patients. Neuropsychopharmacology 28: 2020–2028PubMedGoogle Scholar
  32. Krystal JH, Petrakis IL, Webb E, Cooney NL, Karper LP, Namanworth S et al (1998) Dose-related ethanol-like effects of the NMDA antagonist, ketamine, in recently detoxified alcoholics. Arch Gen Psychiatry 55: 354–360PubMedCrossRefGoogle Scholar
  33. Lee SL, Hoog JO, Yin SJ (2004) Functionality of allelic variations in human alcohol dehydrogenase gene family: assessment of a functional window for protection against alcoholism. Pharmacogenetics 14: 725–732PubMedCrossRefGoogle Scholar
  34. Mann K, Lehert P, Morgan MY (2004) The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis. Alcohol Clin Exp Res 28: 51–63PubMedCrossRefGoogle Scholar
  35. Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE et al (1997) Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature 389: 385–389PubMedCrossRefGoogle Scholar
  36. Miyakawa T, Yagi T, Kitazawa H, Yasuda M, Kawai N, Tsuboi K et al (1997) Fyn-kinase as a determinant of ethanol sensitivity: relation to NMDA-receptor function. Science 278: 698–701PubMedCrossRefGoogle Scholar
  37. Mizoi Y, Yamamoto K, Ueno Y, Fukunaga T, Harada S (1994) Involvement of genetic polymorphism of alcohol and aldehyde dehydrogenases in individual variation of alcohol metabolism. Alcohol Alcohol 29: 707–710PubMedGoogle Scholar
  38. Neumark YD, Friedlander Y, Durst R, Leitersdorf E, Jaffe D, Ramchandani VA et al (2004) Alcohol dehydrogenase polymorphisms influence alcohol-elimination rates in a male Jewish population. Alcohol Clin Exp Res 28: 10–14PubMedCrossRefGoogle Scholar
  39. Olive MF, Mehmert KK, Koenig HN, Camarini R, Kim JA, Nannini MA et al (2003) A role for corticotropin releasing factor (CRF) in ethanol consumption, sensitivity, and reward as revealed by CRF-deficient mice. Psychopharmacology 165: 181–187PubMedGoogle Scholar
  40. Oroszi G, Goldman D (2004) Alcoholism: genes and mechanisms. Pharmacogenomics 5: 1037–1048PubMedCrossRefGoogle Scholar
  41. Pagan JL, Rose RJ, Viken RJ, Pulkkinen L, Kaprio J, Dick DM (2006) Genetic and environmental influences on stages of alcohol use across adolescence and into young adulthood. Behav Genet 36: 483–497PubMedCrossRefGoogle Scholar
  42. Petrakis IL, Limoncelli D, Gueorguieva R, Jatlow P, Boutros NN, Trevisan L et al (2004) Altered NMDA glutamate receptor antagonist response in individuals with a family vulnerability to alcoholism. Am J Psychiatry 161: 1776–1782PubMedCrossRefGoogle Scholar
  43. Prescott CA (2002) Sex differences in the genetic risk for alcoholism. Alcohol Res Health 26: 264–273PubMedGoogle Scholar
  44. Prescott CA, Caldwell CB, Carey G, Vogler GP, Trumbetta SL, Gottesman II (2005) The Washington University Twin Study of alcoholism. Am J Med Genet B Neuropsychiatr Genet 134: 48–55PubMedGoogle Scholar
  45. Schuckit MA, Mazzanti C, Smith TL, Ahmed U, Radel M, Iwata N et al (1999) Selective genotyping for the role of 5-HT2A, 5-HT2C, and GABA alpha 6 receptors and the serotonin transporter in the level of response to alcohol: a pilot study. Biol Psychiatry 45: 647–651PubMedCrossRefGoogle Scholar
  46. Sillaber I, Rammes G, Zimmermann S, Mahal B, Zieglgänsberger W, Wurst W et al (2002) Enhanced and delayed stress-induced alcohol drinking in mice lacking functional CRH1 receptors. Science 296: 931–933PubMedCrossRefGoogle Scholar
  47. Spanagel R, Herz A, Shippenberg TS (1992) Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci U S A 89: 2046–2050PubMedCrossRefGoogle Scholar
  48. Spanagel R, Pendyala G, Abarca C, Zghoul T, Sanchis-Segura C, Magnone MC et al (2005) The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption. Nat Med 11: 35–42PubMedCrossRefGoogle Scholar
  49. Tanda G, Pontieri FE, Di Chiara G (1997) Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science 276: 2048–2050PubMedCrossRefGoogle Scholar
  50. Tsai G, Gastfriend DR, Coyle JT (1995) The glutamatergic basis of human alcoholism. Am J Psychiatry 152: 332–340PubMedGoogle Scholar
  51. Tyndale RF (2003) Genetics of alcohol and tobacco use in humans. Ann Med 35: 94–121PubMedCrossRefGoogle Scholar
  52. Volpicelli JR, Watson NT, King AC, Sherman CE, O'Brien CP (1995) Effect of naltrexone on alcohol "high" in alcoholics. Am J Psychiatry 152: 613–615PubMedGoogle Scholar
  53. Wall TL, Carr LG, Ehlers CL (2003) Protective association of genetic variation in alcohol dehydrogenase with alcohol dependence in Native American Mission Indians. Am J Psychiatry 160: 41–46PubMedCrossRefGoogle Scholar
  54. Wiedemann K, Jahn H, Yassouridis A, Kellner M (2001) Anxiolyticlike effects of atrial natriuretic peptide on cholecystokinin tetrapeptide-induced panic attacks: preliminary findings. Arch Gen Psychiatry 58: 371–377PubMedCrossRefGoogle Scholar
  55. Wiesbeck GA, Weijers HG, Lesch OM, Glaser T, Toennes PJ, Boening J (2001) Flupenthixol decanoate and relapse prevention in alcoholics: results from a placebo-controlled study. Alcohol Alcohol 36: 329–334PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jakob Hein
  • Michael Rapp
  • Andreas Heinz
    • 1
  1. 1.Universitätsklinik für Psychiatrie und Psychotherapie, Charité – Universitätsmedizin BerlinBerlinGermany

Personalised recommendations