Nervenheilkunde 2003; 22(01): 19-23
DOI: 10.1055/s-0038-1624365
Original- und Übersichtsarbeiten/Original and Review Articles
Schattauer GmbH

Neuroendokrinologie der Alkoholabhängigkeit

Einfluss auf Affekt, Alkoholappetenz und CravingNeuroendocrinology of alcoholismeffects upon emotions and craving
F. Kiefer
1   Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Hamburg-Eppendorf
,
K. Wiedemann
1   Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Hamburg-Eppendorf
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
15. Januar 2018 (online)

Zusammenfassung

Insbesondere zwei psychiatrisch relevante Krankheitsbilder, die affektiven Störungen und die Störungen der Appetitregulation, werden aktuell durch Impulse aus der neuroendokrinologischen Forschung neuen biologischen Erklärungsmodellen zugänglich. Eine besondere Bedeutung kommt hierbei den Peptiden der HypothalamusHypophysen-Nebennierenrinden-Achse (HHN-Achse) zu, neuerdings aber auch weiteren modulierenden Neuropeptiden wie z.B. dem Leptin, dem atrialen natriuretischen Peptid (ANP) und dem β-Endorphin. Obwohl seit langer Zeit bekannt ist, dass sowohl Störungen der Stresshormon-Achse (HHN) als auch Störungen der Affektivität und der Appetitregulation bei Alkoholabhängigen ausgeprägt vorhanden sind, war der Einfluss von Neuropeptiden auf psychopathologische Veränderungen bei Alkoholabhängigkeit nur selten Gegenstand spezifischer Studien. Die vorliegende Übersicht fasst aktuelle Studien über die Wechselwirkungen zwischen Endokrinum und affektiven Syndromen sowie Suchtdruck bei der Alkoholabhängigkeit zusammen.

Summary

Impact of neuroendocrinologic research has been demonstrated especially regarding the regulation of affect and appetite. One well known central mechanism of action is the hypothalamic-pituitary-adrenocortical (HPA) axis, but moreover, some modulating peptides like leptin, atrial natriuretic peptide (ANP) and β-endorphin have been shown to reveal new insights and perspectives in the regulation of this system. Whereas disturbances of the HPA axis as well as disturbances in the regulation of affect and appetite occur regularly in alcohol addicts, interactions of neuropeptides and psychopathology in alcoholism have been studied rather seldom. This article summarizes some recent results on this topic.

 
  • Literatur

  • 1 Heim C, Nemeroff CB. Neurobiology of early life stress: Clinical studies. Semin Clin Neuropsychiatry 2002; 07: 147-59.
  • 2 Kandel ER. A new intellectual framework for psychiatry. Am J Psychiatry 1998; 155: 457-69.
  • 3 Fulton S, Woodside B, Shizgal P. Modulation of brain reward circuitry by leptin. Science 2000; 287: 125-8.
  • 4 O’Malley SS, Krishnan-Sarin S, Farren C, Sinha R, Kreek J. Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamopituitary-adrenocortical axis. Psychopharmacology (Berl) 2002; 160: 19-29.
  • 5 Adinoff B, Martin PR, Bone GHA. et al. Hpothalamic-pituitary-adrenal axis functioning and cerebrospinal fluid corticotropin releasing hormone and corticotropin levels in alcoholics after recent and long-term abstinence. Arch Gen Psychiat 1990; 47: 325-30.
  • 6 Adinoff B, Risher DFlowers, De Jong J. et al. Disturbances of hypothalamic-pituitary-adrenal axis functioning during ethanol withdrawal in six men. Am J Psychiatry 1991; 148: 1023-5.
  • 7 Tabakoff B, Jaffe RC, Ritzmann RF. Corticosterone concentrations in mice during etanol drinking and withdrawal. J Pharmacol Exp Ther 1978; 30: 371-4.
  • 8 Heuser I, von Bardeleben U, Boll E, Holsboer F. Response of ACTH and cortisol to human corticotropin-releasing hormone after shortterm abstention from alcohol abuse. Biol Psychiat 1988; 24: 316-21.
  • 9 Costa A, Bono G, Martignoni E, Merlo P, Sances G, Nappi G. An assessment of hypothalamo-pituitary-adrenal axis functioning in non-depressed, early abstinent alcoholics. Psychoneuroendocrinology 1996; 21: 263-75.
  • 10 Bleuler M. Endokrinologische Psychiatrie. Stuttgart: Georg Thieme Verlag 1954
  • 11 Holsboer F, von Bardeleben U, Buller R, Heuser I, Steiger A. Stimulation response to corticotropin-releasing hormone in patients with depression, alcoholism and panic disorder. Horm Metab Res 1987; 16 suppl: 80-8.
  • 12 von Bardeleben U, Heuser I, Holsboer F. Human CRH stimulation response during acute withdrawal and after medium-term abstention from alcohol abuse. Psychoneuroendocrinology 1989; 14: 441-9.
  • 13 Sillaber I, Rammes G, Zimmermann S. et al. Enhanced and delayed stress-induced alcohol drinking in mice lacking functional CRH1 receptors. Science 2002; 296: 931-3.
  • 14 Munck A, Guyre PM, Holbrook NJ. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocrinol Rev 1984; 05: 25-44.
  • 15 Sapolsky RM, Krey LC, McEwen BS. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev 1986; 07: 284-301.
  • 16 Adinoff B. The alcohol withdrawal syndrome: Neurobiology of treatment and toxicity. Am J Psych 1994; 03: 277-88.
  • 17 Roberts AJ, Lessov CN, Phillips TJ. Critical role for glucocorticoid receptors in stress and ethanol-induced locomotor sensitization. J Pharmacol Exp Ther 1995; 275: 790-7.
  • 18 Roberts AJ, Chu HP, Crabbe JC, Keith LD. Differential modulation by the stress axis of ethanol withdrawal seizure expression in WSP and WSR mice. Alcohol Clin Exp Res 1991; 15: 412-16.
  • 19 Menzaghi F, Rassnick S, Heinrichs S. et al. The role of corticotropin-releasing factor in the anxiogenic effects of ethanol withdrawal. Ann N Y Acad Sci 1994; 739: 176-84.
  • 20 Adinoff B, Iranmanesh A, Veldhuis J, Fisher L. Disturbance of the stress response – the role of the HPA axis during alcohol withdrawal and abstinence. Alcohol Health and Research World 1998; 22: 67-73.
  • 21 Deroche V, Marinelli M, Maccari S, Le Moal M, Simon H, Piazza PV. Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamin-dependent locomotor effects of amphetamine and morphine depends on stressinduced corticosterone secretion. J Neurosci 1995; 15: 7181-8.
  • 22 Kiefer F, Jahn H, Kellner M, Naber D, Wiedemann K. Leptin as a possible modulator of craving for alcohol. Arch Gen Psychiatry 2001; 58: 509-10.
  • 23 Kiefer F, Jahn H, Jaschinski M. et al. Leptin: a modulator of alcohol craving?. Biol Psychiatry 2001; 49: 782-7.
  • 24 Nicolás JM, Fernández-Solà J, Fatló F. et al. Increased circulating leptin levels in chronic alcoholism. Alcohol Clin Exp Res 2001; 25: 83-8.
  • 25 Obradovic T, Meadows GG. Chronic ethanol consumption increases plasma leptin levels and alters leptin receptors in the hypothalamus and the perigonadal fat of C57BL/6 mice. Alcohol Clin Exp Res 2002; 26: 255-62.
  • 26 Kiefer F, Jahn H, Wolf K, Kampf P, Knaudt K, Wiedemann K. Free-choice alcohol consumption in mice after application of the appetite regulating peptide leptin. Alcohol Clin Exp Res 2001; 25: 787-9.
  • 27 Spanagel R, Holter SM. Long-term alcohol self-administration with repeated alcohol deprivation phases: an animal model of alcoholism?. Alcohol & Alcoholism 1999; 34: 231-43.
  • 28 Lin HZ, Yang SQ, Zeldin G, Diehl AM. Chronic ethanol consumption induces the production of tumor necrosis factor-alpha and related cytokines in liver and adipose tissue. Alcohol Clin Exp Res 1998; 22: 231-7.
  • 29 Barbier M, Cherbut C, Aube AC, Blottiere HM, Galmiche JP. Elevated plasma leptin concentrations in early stages of experimental intestinal inflammation in rats. Gut 1998; 43: 783-90.
  • 30 Kiefer F, Jahn H, Schick M, Wiedemann K. Alcohol intake, TNF-alpha, leptin and craving: factors of a possibly vicious circle?. Alcohol & Alcoholism 2002; 37 (04) 401-4.
  • 31 De Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 1981; 28: 89-94.
  • 32 Cantin M, Genest J. The heart as an endocrine gland. Hypertension 1987; 10 (Suppl. I): 118-21.
  • 33 Gutkowska J, Nemer M. Structure expression and function of atrial natriuretic factor in extra atrial tissues. Endocr Rev 1989; 10: 519-36.
  • 34 Samson WK. Dehydratation-induced alterations in rat brain vasopressin and atrial natriuretic factor immunoreactivity. Endocrinology 1985; 117: 1279-81.
  • 35 Gutkowska J, Cantin M, Genest J, Sirois P. Release of immunoreactive atrial natriuretic factor from the isolated perfused rat lungs. FEBS Lett 1987; 214: 17-20.
  • 36 Imura H, Nakao K, Itoh H. The natriuretic peptide system in the brain: Implications of the central control of cardiovascular and neuroendocrine functions. Front Neuroendocrinol 1992; 13: 217-49.
  • 37 Kellner M, Wiedemann K, Holsboer F. Atrial natriuretic factor inhibits the CRH-stimulated secretion of ACTH and cortisol in man. Life Sciences 1992; 50: 1835-42.
  • 38 Jessop DS. Central non-glucocorticoid inhibitors of the hypothalamopituitary-adrenal axis. J Endocrinol 1999; 160: 169-80.
  • 39 Wiedemann K. Effects of peptidergic factors in anxiety and stress. Eur Arch Psychiat Clin Neuroscience 1998; 248: 7.
  • 40 Wiedemann K, Jahn H, Yassouridis A, Kellner M. Anxiolyticlike effects of atrial natriuretic peptide on cholecystokinin tetrapeptide-induced panic attacks: preliminary findings. Arch Gen Psychiatry 2001; 58: 371-7.
  • 41 Bidzseranova A, Gueron J, Toth G, Penke B, Varga J, Teledgy G. Behavioral effects of atrial natriuretic and brain natriuretic peptides in rats. Neuroreport 1992; 03: 283-5.
  • 42 Bhattacharya SK, Chakrabarti A, Sandler M, Glover V. Anxiolytic activity of intraventriculary administered atrial natriuretic peptide in the rat. Neuropsychopharmacology 1996; 15: 199-206.
  • 43 Poggioli R, Vergoni AV, Rasori E, Marrama D, Bertolini A. Behavioral effects of atriopeptin in rats. Neuropeptides 1992; 22: 149-54.
  • 44 Strohle A, Jahn H, Montkowski A. et al. Central and peripheral administration of atriopeptin is anxiolytic in rats. Neuroendocrinology 1997; 65: 210-5.
  • 45 Kellner M, Herzog L, Yassouridis A, Holsboer F, Wiedemann K. Possible role of atrial natriuretic hormone in pituitary-adrenocortical unresponsiveness in lactate-induced panic. Am J Psychiatry 1995; 152: 1365-7.
  • 46 Strohle A, Kellner M, Holsboer F, Wiedemann K. Anxiolytic activity of atrial natriuretic peptide in patients with panic disorder. Am J Psychiatry 2001; 158: 1514-6.
  • 47 Kovacs GL. Alpha-atrial natriuretic peptide attenuates ethanol withdrawal symptoms. Eur J Pharmacol 1993; 238: 417-9.
  • 48 Kiefer F, Andersohn F, Jahn H, Wolf K, Wiedemann K. Involvement of plasma ANP in protracted alcohol withdrawal. Acta Psychiatrica Scandinavica 2002; 105: 65-70.
  • 49 Naber D. Clinical relevance of endorphins in psychiatry. Prog Neuropsychopharmacol Biol Psychiatry 1988; 12: 119-35.
  • 50 Giannini AJ, Melemis SM, Martin DM, Folts DJ. Symptoms of premenstrual syndrome as a function of beta-endorphin: two subtypes. Progress in Neuro-Psychopharmacology & Biological Psychiatry 1994; 18: 321-7.
  • 51 Meador-Woodruff JH, Haskett RF, Grunhaus L, Akil H, Watson SJ, Greden JF. Postdexamethasone plasma cortisol and beta-endorphin levels in depression: relationship to severity of illness. Biol Psychiatry 1987; 22: 1137-50.
  • 52 de Waele JP, Kiianmaa K, Gianoulakis C. Spontaneous and ethanol-stimulated in vitro release of betaendorphin by the hypothalamus of AA and ANA rats. Alcoholism: Clinical & Experimental Research 1994; 18: 1468-73.
  • 53 Patel VA, Pohorecky LA. Acute and chronic ethanol treatment on beta-endorphin and catecholamine levels. Alcohol 1989; 06: 59-63.
  • 54 Lukas SE, Mendelson JH. Electroencephalographic activity and plasma ACTH during ethanol-induced euphoria. Biol Psychiatry 1988; 23: 141-8.
  • 55 Sher L. The role of the endogenous opioid system in the pathogenesis of anxiety disorders. Med Hypotheses 1998; 50: 473-4.
  • 56 Borg S, Kvande H, Rydberg U, Terenius L, Wahlstrom A. Endorphin levels in human cerebrospinal fluid during alcohol intoxication and withdrawal. Psychopharmacology (Berl) 1982; 78: 101-3.
  • 57 Vescovi PP, Coiro V, Volpi R, Giannini A, Passeri M. Plasma beta-endorphin, but not met-enkephalin levels are abnormal in chronic alcoholics. Alcohol Alcohol 1992; 27: 471-5.
  • 58 Esel E, Sofuoglu S, Aslan SS, Kula M, Yabanoglu I, Turan MT. Plasma levels of beta-endorphin, adrenocorticotropic hormone and cortisol during early and late alcohol withdrawal. Alcohol Alcohol 2001; 36: 572-6.
  • 59 Kiefer F, Horntrich M, Jahn H, Wiedemann K. Is withdrawal-induced anxiety in alcoholism based on beta-endorphin deficiency?. Psychopharmacology 2002; 162: 433-7.
  • 60 Gianoulakis C. Endogenous opioids and excessive alcohol consumption. J Psychiatry Neurosci 1993; 18: 148-56.
  • 61 Wand GS, Mangold D, El Deiry S, McCaul ME, Hoover D. Family history of alcoholism and hypothalamic opioidergic activity. Arch Gen Psychiatry 1998; 55: 1114-9.
  • 62 Hundt W, Zimmermann U, Pottig M, Spring K, Holsboer F. The combined dexamethasonesuppression/CRH-stimulation test in alcoholics during and after acute withdrawal. Alcohol Clin Exp Res 2001; 25: 687-91.
  • 63 Timpl P, Spanagel R, Sillaber I. et al. Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor. Nature Genetics 1998; 19: 162-6.