, Volume 68, Issue 3, pp 221–227 | Cite as

Acute and chronic ethanol treatment changes endorphin levels in brain and pituitary

  • Rüdiger Schulz
  • Michael Wüster
  • Theodora Duka
  • Albert Herz
Original Investigations


Acute ethanol administration increased methionine-enkephalin (met-enkephalin) and β-endorphin levels in distinct areas of the rat brain, whereas chronically supplied ethanol caused a depression of met-enkephalin and β-endorphin levels in most of the brain areas investigated. The β-endorphin content of the intermediate/posterior lobe of the pituitary of rats and guinea pigs decreased by 70%. Withdrawal of ethanol resulted in a complete recovery of endorphin levels in brain and pituitary within two weeks. Whether the observed alterations in endorphin concentrations are causally related to the primary mechanisms under-lying alcohol dependence is uncertain, since no obvious signs of physical dependence were observed in treated animals.

Key words

Endorphin Enkephalin Ethanol Tolerance/Dependence 


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  1. Beaumont, A., Hughes, J.: Biology of opioid peptides. Ann. Rev. Pharmacol. Toxicol. 19, 245–267 (1979)Google Scholar
  2. Blum, K., Hamilton, M. G., Wallace, J. E.: Alcohol and opiates: A review of common neurochemical and behavioural mechanisms. In: Alcohol and opiates, K. Blum, ed., pp. 203–236. New York: Academic Press 1977Google Scholar
  3. Cavey, C. V.: Alcoholism — a biological approach. Trends in Neurosciences 2, 23–25 (1979)Google Scholar
  4. Cicero, T. J., Badger, T. M.: A comparative analysis of the effects of narcotics, alcohol and the barbiturates on the hypothalamic-pituitary-gonadal axis. In: Advances in experimental medicine and biology, vol. 85, M. M. Gross, ed., pp. 95–115. New York, London: Plenum Press 1977Google Scholar
  5. Cox, B. M., Baizman, E. R., Su, T., Osman, O. H., Goldstein, A.: Further studies on the nature and functions of pituitary endorphins. In: Advances in biomedical psychopharmacology, vol. 18, E. Costa, M. Trabucchi, eds., pp. 183–189. New York: Raven Press 1978Google Scholar
  6. Duka, Th., Höllt, V., Przewłocki, R., Wesche, D.: Distribution of methionine- and leucine-enkephalin within the rat pituitary gland measured by highly specific radioimmunoassay. Biochem. Biophys. Res. Commun. 85, 1119–1127 (1978)Google Scholar
  7. Duka, Th., Wüster, M., Herz, A.: Rapid changes of enkephalin levels in rat striatum and hypothalamus induced by diazepam. Naunyn Schmiedebergs Arch. Pharmacol. 309, 1–5 (1979)Google Scholar
  8. Ellingboe, J.: Effects of alcohol on neurochemical processes. In: Psychopharmacology: A generation of progress, M. A. Lipton, A. DiMascio, K. F. Killam, eds., pp. 1653–1664. Raven Press: New York 1978Google Scholar
  9. Glowinski, J., Iversen, L. L.: Regional studies of catecholamines in the rat brain. J. Neurochem. 13, 655–669 (1966)Google Scholar
  10. Goldstein, D. B., Pal, N.: Alcohol dependence produced in mice by inhalation of ethanol: Grading the withdrawal reaction. Science 172, 288–290 (1971)Google Scholar
  11. Hill, M. W., Bangham, A. D.: General depressant drug dependency: A biophysical hypothesis. In: Advances in experimental medicine and biology, vol. 59, M. M. Gross, ed., pp. 1–9. New York, London: Plenum Press 1975Google Scholar
  12. Höllt, V., Przewłocki, R., Herz, A.: β-Endorphin-like immuno-reactivity in plasma, pituitaries and hypothalamus of rats following treatment with opiates. Life Sci. 23, 1057–1066 (1978)Google Scholar
  13. Höllt, V., Przewłocki, R., Bergmann, M., Haarmann, I., Duka, Th.: Increased biosynthesis of β-endorphin in the pars intermedia of rat pituitaries after long-term treatment with haloperidol. In: Endogenous and exogenous opiate agonists and antagonists, E. L. Way, ed. New York: Pergamon Press (in press) 1979aGoogle Scholar
  14. Höllt, V., Gramsch, Ch., Herz, A.: Immunoassay of β-endorphin. In: Radioimmunoassay of drugs and hormones in cardiovascular medicine, A. Albertini, M. DaPrada, eds., pp. 293–307, Amsterdam: Elsevier/North-Holland Biomedical Press 1979bGoogle Scholar
  15. Hong, J. S., Yang, H.-Y. T., Fratta, W., Costa, E.: Rat striatal methionine-enkephalin content after chronic treatment with cataleptogenic and noncataleptogenic antischizophrenic drugs. J. Pharmacol. Exp. Ther. 205, 141–147 (1978)Google Scholar
  16. Kalant, H.: Direct effects of ethanol on the nervous system. Fed. Proc. 34, 1930–1941 (1975)Google Scholar
  17. Kalant, H.: Biochemical aspects of tolerance to, and physical dependence on, central depressants. In: Proc. Eur. Soc. Neurochem, vol. 1, V. Neuhoff, ed., pp. 317–331. Weinheim, New York: Verlag Chemie 1978Google Scholar
  18. Liljequist, S.: Effects of dependence-producing drugs on neurotransmitters and neuronal excitability. In: Proc. Eur. Soc. Neurochem. vol. 1, V. Neuhoff, ed., pp. 359–373. Weinheim, New York: Verlag Chemic 1978Google Scholar
  19. Liljequist, S., Carlsson, A.: Alteration of central catecholamine metabolism following acute administration of ethanol. J. Pharm. Pharmacol. 30, 728–730 (1978)Google Scholar
  20. Mains, R. E., Eipper, B. A., Ling, N.: Common precursor to corticotropins and endorphins. Proc. Natl. Acad. Sci. USA 74, 3014–3018 (1977)Google Scholar
  21. Mains, R. E., Eipper, B. A.: Studies on the common precursor to ACTH and endorphin. In: Endorphins '78, L. Gráf, M. Palkovits, A. Z. Ronai, eds., pp. 79–120. Amsterdam 1978Google Scholar
  22. Marks, V.: Biochemical and metabolic basis of alcohol toxicity. In: Advances in biological psychiatry, vol. 3, J. Medlewicz, H. M. van Praag, eds., pp. 88–96. Basel, München, Paris: Karger 1979Google Scholar
  23. Merry, J.: Hypothalamic-pituitary-adrenal function in chronic alcoholics. In: Advances in experimental medicine and biology, vol. 35, M. M. Gross, ed., pp. 167–179. New York, London: Plenum Press 1973Google Scholar
  24. Miyahara, J. T., Esplin, D. W., Zablocka, B.: Differential effects of depressant drugs on presynaptic inhibition. J. Pharmacol. Exp. Ther. 134, 118 (1966)Google Scholar
  25. Ogawa, N., Panerai, A. E., Lee, S., Forsback, G., Havlicek, V., Friesen, H. G.: β-Endorphin concentration in the brain of intact and hypophysectomized rats. Life Sci. 25, 317–326 (1979)Google Scholar
  26. Przewlocki, R., Höllt, V., Duka, Th., Kleber, G., Gramsch, Ch., Haarmann, I., Herz, A.: Long-term morphine treatment decreases endorphin levels in rat brain and pituitary. Brain Res. 174, 357–361 (1979)Google Scholar
  27. Rossier, J., Battenberg, E., Pittman, Q., Bayon, A., Koda, L., Miller, R., Guillemin, R., Bloom, F.: Hypothalamic enkephalin neurons may regulate the neurohypophysis. Nature 277, 653–655 (1979)Google Scholar
  28. Sharman, A., Seeman, P.: The impulse-blocking concentrations of anesthetics, alcohols, anticonvulsants, barbiturates and narcotics on phrenic and sciatic nerves. Can. J. Physiol. Pharmacol. 52, 535–540 (1974)Google Scholar
  29. Smith, C. M.: The pharmacology of sedative/hynotics, alcohol, and anesthetics: Sites and mechanisms of action. In: Handbuch der Experimentellen Pharmakologie, Vol. 45/1, N. R. Martin, ed., pp. 413–587. Berlin, Heidelberg, New York: Springer 1977Google Scholar
  30. Wallgren, H., Virtanen, P.: Membrane effects of alcohol in the nervous system. In: Proc. Europ. Soc. Neurochem., vol. 1, V. Neuhoff, ed., pp. 346–358. Weinheim, New York: Verlag Chemie 1978Google Scholar
  31. Weber, E., Voigt, K. H., Martin, R.: Concomitant storage of ACTH-and endorphin-like immunoreactivity in the secretory granules of anterior pituitary corticotrophs. Brain Res. 157, 385–390 (1978)Google Scholar
  32. Wright, J.: Endocrine effects of alcohol. Clin. Endocrinol. Metab. 7, 351–367 (1978)Google Scholar
  33. Wüster, M., Schulz, R., Herz, A.: Inquiry into endorphinergic feedback mechanisms during the development of opiate tolerance/dependence. Brain Res. (in press 1980)Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Rüdiger Schulz
    • 1
  • Michael Wüster
    • 1
  • Theodora Duka
    • 1
  • Albert Herz
    • 1
  1. 1.Department of NeuropharmacologyMax-Planck-Institute of PsychiatryMünchen 40Germany

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