Hypothalamic-Pituitary Function during Alcohol Exposure and Withdrawal and Cocaine Exposure

  • Jeffery N. Wilkins
  • David A. Gorelick
  • Koonlawee Nademanee
  • Anna Taylor
  • David S. Herzberg
Part of the Recent Developments in Alcoholism book series (RDIA, volume 10)


This chapter examines the neuroendocrine effects of acute exposure to and withdrawal from alcohol and cocaine, with special emphasis on the hypothalamic-pituitary-adrenal (HPA) axis. We present the results from two preliminary controlled inpatient studies that document HPA dysfunction during acute exposure to alcohol and cocaine and during withdrawal from alcohol. We discuss the methodological approach of these studies in comparison to related attempts in the literature to use measures of thyroid and prolactin regulation to predict risk of relapse to alcohol and cocaine use, respectively. Our data and the results of related studies are presented in the context of a proposed index of HPA axis dysfunction that may provide a useful clinical measure of susceptibility to relapse during protracted abstinence from alcohol or cocaine.


Cortisol Level Cortisol Response Alcohol Exposure Alcohol Withdrawal Cocaine Dependence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gorelick DA, Wilkins JN: Special aspects of human alcohol withdrawal, in Galanter M (ed): Recent Developments in Alcoholism, Vol. IV New York, Plenum Press, 1986, p 285-1285.Google Scholar
  2. 2.
    Loosen PT, Dew BW, Prange AJ: Long-term predictors of outcome in abstinent alcoholic men. Am J Psychiatry 147:1662–1666, 1990.PubMedGoogle Scholar
  3. 3.
    Teoh SK, Mendelson JH, Mello NK, Weiss R, McElroy S, McAfee B: Hyperprolactinemia and risk for relapse of cocaine abuse. Biol Psychiatry 28:824–828, 1990.PubMedCrossRefGoogle Scholar
  4. 4.
    Mendelson JH, Teoh SK, Lange U, Mello NK, Weiss R, Skupny A, Ellingboe J: Anterior pituitary, adrenal, and gonadal hormones during cocaine withdrawal. Am J Psychiatry 145(9):1094–1098, 1988.PubMedGoogle Scholar
  5. 5.
    Wilkins JN, Gorelick DA, Bamshad BR, Setoda DY: Elevated serum prolactin levels in newly abstinent male cocaine abusers. Society for Neuroscience, Toronto, Canada, November 1988 (abstract).Google Scholar
  6. 6.
    Martin WR, Jasiriski DR: Physiological parameters of morphine dependence in man—tolerance, early abstinence, protracted abstinence. J Psychiatr Res 1969(7):9–17.PubMedCrossRefGoogle Scholar
  7. 7.
    Himmelsbach CK: Clinical studies of drug addiction—physical dependence, withdrawal and recovery. Arch Intern Med 69:766, 1942.CrossRefGoogle Scholar
  8. 8.
    Martin WR, Jasinski DR, Sapira JD, Flanary HG, Kelly OA, Thompson AK, Logan CR: The respiratory effects of morphine during a cycle of dependence. J Pharmacol Exp Ther 162:182, 1968.PubMedGoogle Scholar
  9. 9.
    Merry J, Marks V: Plasma-hydrocortisone response to ethanol in chronic alcoholics. Lancet 921-923, 1969 (preliminary communications).Google Scholar
  10. 10.
    Bailly D, Dewailly D, Beuscart R, Couplet G, Dumont P, Racadot A, Fossati P, Parquet PJ: Adrenocorticotropin and cortisol responses to ovine corticotropin-releasing factor in alcohol dependence disorder. Preliminary report. Hormone Res 31(1–2):72–75, 1989.PubMedCrossRefGoogle Scholar
  11. 11.
    von Bardeleben U, Heuser I, Holsboer F: Human CRH stimulation response during acute withdrawal and after medium-term abstention from alcohol abuse. Psychoneuroendocrinology 14(6):441–449, 1989.CrossRefGoogle Scholar
  12. 12.
    Rivier C, Imaki T, Vale W: Prolonged exposure to alcohol: Effect on CRF mRNA levels, and CRF-and stress-induced ACTH secretion in the rat. Brain Res 520(1–2):1–5, 1990.PubMedCrossRefGoogle Scholar
  13. 13.
    George SR, Fan T, Roldan L, Naranjo CA: Corticotropin-releasing factor is altered in brains of animals with high preference for ethanol. Alcohol Clin Exp Res 14(3):425–429, 1990.PubMedCrossRefGoogle Scholar
  14. 14.
    Redei E, Branch BJ, Gholami S, Lin EY, Taylor AN: Effects of ethanol on CRF release in vitro. Endocrinology 123(6):2736–2743, 1988.PubMedCrossRefGoogle Scholar
  15. 15.
    Moldow RL, Fischman AJ: Cocaine induced secretion of ACTH, beta-endorphin, and corticosterone. Peptides 8(5):819–822, 1987.PubMedCrossRefGoogle Scholar
  16. 16.
    Pilotte NS, Sharpe LG, Dax EM: Multiple, but not acute, infusions of cocaine alter the release of prolactin in male rats. Brain Res 512(11):107–112, 1990.PubMedCrossRefGoogle Scholar
  17. 17.
    Goeders NE, Bienvenu OJ, De Souza EB: Chronic cocaine administration alters corticotropin-releasing factor receptors in the rat brain. Brain Res 531(1–2):322–328, 1990.PubMedCrossRefGoogle Scholar
  18. 18.
    Rivier C, Vale W: Cocaine stimulates adrenocorticotropin (ACTH) secretion through a corticotropin-releasing factor (CRF)-mediated mechanism. Brain Res 422(2):403–406, 1987.PubMedCrossRefGoogle Scholar
  19. 19.
    Wilkins JN, Shaner AL, Patterson CM, Setoda D, Gorelick D: Discrepancies between patient report, clinical assessment, and urine analysis in psychiatric patients during inpatient admission. Psychopharmacol Bull 27(2):149–154, 1991.PubMedGoogle Scholar
  20. 20.
    Gorelick DA, Paredes A: Effect of fluoxetine on alcohol intake in male alcoholics. Alcoholism: Clinical and Experimental Research (in press).Google Scholar
  21. 21.
    Van Thiel DH: Alcohol and its effect on endocrine functioning. Alcoholism 4:44–49, 1980.PubMedGoogle Scholar
  22. 22.
    Morgan MY: Alcohol and the endocrine system. Br Med Bull 38:17–20, 1982.Google Scholar
  23. 23.
    Valimaki M, Palkonen R, Harkonen, M, Yilkahri R: Hormonal changes in noncirrhotic male alcoholics during ethanol withdrawal. Alcohol Alcoholism 19(3):235–242, 1984.Google Scholar
  24. 24.
    Willenbring ML, Morley JE, Niewochner CB, Heilman RO, Carlson CH, Shafer RB: Adrenocortical hyperactivity in newly admitted alcoholics: prevalence, course, and associated variables. Psychoneuroendocrinology 9:415–422, 1984.PubMedCrossRefGoogle Scholar
  25. 25.
    Risher-Flowers D, Adinoff B, Ravitz B, Bone GH, Martin PR, Nutt D, Linnoila M: Circadian rhythms of cortisol during alcohol withdrawal. Adv Alcohol Substance Abuse 7(3–4):37–41, 1988.CrossRefGoogle Scholar
  26. 26.
    Mander AJ, Young A, MacDonald TM, Williams BC, Waugh CJ, Edwards CR: Blood pressure, renin-angiotensin-aldosterone axis and cortisol changes during withdrawal from alcohol. Alcohol Alcoholism 24(5):409–414, 1989.Google Scholar
  27. 27.
    Targum SD, Wheadon DE Chastek CT, et al.: Dysregulation on hypothalamic-pituitaryadrenal function in depressed alcoholic patients. J Affect Dis 4:347–353, 1982.PubMedCrossRefGoogle Scholar
  28. 28.
    Targum SD, Capodanno AE, Unger S, et al.: Abnormal dexamethasone tests in withdrawing alcoholic patients. Bid Psychiatry 19(3):401–405, 1984.Google Scholar
  29. 29.
    Abou-Saleh MT, Merry J, Coppen A: Dexamethasone suppression test in alcoholism. Acta Psychiatr Scand 69:112–116, 1984.PubMedCrossRefGoogle Scholar
  30. 30.
    Coopen A, Abou-Saleh M, Milln P, et al.: Dexamethasone suppression test in depression and other psychiatric illness. Br J Psychiatry 142:498–504, 1983.CrossRefGoogle Scholar
  31. 31.
    Newsom G, Murray N: Reversal of dexamethasone suppression test nonsuppression in alcohol abusers. Am J Psychiatry 140:3, 1983.Google Scholar
  32. 32.
    Ravi SD, Dorus W, Park YN, et al.: The dexamethasone suppression test and depressive symptoms in early and late withdrawal from alcohol. Am J Psychiatry 141(11):1445–1448, 1984.PubMedGoogle Scholar
  33. 33.
    Dackis CA, Bailey J, Pottash ALC, et al.: Specificity of the DST and the TRH test for major depression in alcoholics. Am J Psychiatry 141:680–683, 1984.PubMedGoogle Scholar
  34. 34.
    Carroll BJ, Feinberg M, Greden JF, et al.: A specific laboratory test for the diagnosis of melancholia. Arch Gen Psychiatry 38:15–22, 1981.PubMedCrossRefGoogle Scholar
  35. 35.
    Edelstein CK, Roy-Bryne P, Fawzy FI, et al.: Effects of weight loss on the dexamethasone suppression test. Am J Psychiatry 140:33S–341, 1983.Google Scholar
  36. 36.
    Swartz CM, Dunner FJ: Dexamethasone suppression testing of alcoholics. Arch Gen Psychiatry 39:1309–1312, 1982.PubMedCrossRefGoogle Scholar
  37. 37.
    Rihmer Z, Arato M: Depression and diabetes mellitus. Neuropsychobiology 8:315–318, 1982.PubMedCrossRefGoogle Scholar
  38. 38.
    Wilkins, JN, Carlson HE, Van Vunakis H, et al.: Nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone and prolactin in male chronic smokers. Psycho-pharmacology 78:305–308, 1982.CrossRefGoogle Scholar
  39. 39.
    Burov IV, Treskov VG, Vedernikova NN, Sheveleva OS: Types of alcoholic abstinence and the dexamethasone test (Russian). Z Nevropatol Psikhiatrii Imeni SS Korsakova 87(3):424–428, 1987.Google Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Jeffery N. Wilkins
    • 1
  • David A. Gorelick
    • 2
  • Koonlawee Nademanee
    • 3
  • Anna Taylor
    • 4
  • David S. Herzberg
    • 5
  1. 1.West Los Angeles Veterans Administration Medical Center, Brentwood DivisionSubstance Abuse ServiceLos AngelesUSA
  2. 2.Treatment and Early Intervention Branch, Addiction Research Center, National Institute on Drug Abuse, and Department of PsychiatryUniversity of Maryland School of MedicineBaltimoreUSA
  3. 3.Department of CardiologyDenver General HospitalDenverUSA
  4. 4.Department of Anatomy and Cell BiologyUCLA School of MedicineLos AngelesUSA
  5. 5.West Los Angeles Veterans Administration Medical Center, Brentwood DivisionResearch ServiceLos AngelesUSA

Personalised recommendations