, Volume 127, Issue 1–2, pp 133–139 | Cite as

Facilitation of ethanol consumption by intracerebroventricular infusions of corticosterone

  • C. Fahlke
  • E. H»rd
  • S. Hansen
Original Investigation


Male Wistar rats bearing intracerebroventricular (ICV) cannulae and with simultaneous access to 6% ethanol and water were subjected to adrenalectomy (ADX) or sham surgery. ADX decreased ethanol intake. Starting a few days later, the animals received ICV infusions with 100 μg corticosterone acetate (CORT) with 2-to 3-day intervals for 2 weeks. ICV CORT, but not SC CORT at the same dose, restored ethanol consumption in ADX rats to preoperative levels, whereas vehicle infusions (propylene, glycol) did not. Adrenally intact animals, which normally consumed moderate amounts of ethanol (≈0.5 g/kg per day), also showed a robust effect of ICV infusions of CORT, whereas this facilitatory effect was not observed in high consumers (≈3.0 g/kg per day). The suppressive effect of ADX on ethanol intake was not reproduced by concurrent and repeated ICV infusions of intracellular mineralocorticoid (RU 28318) and glucocorticoid (mifepristone) receptor blockers. It is concluded that CORT stimulates alcohol consumption by acting in the brain, probably by way of neuronal membrane mechanisms.

Key words

Alcohol drinking Adrenalectomy Corticosterone Drug abuse Mifepristone RU 28318 RU 38486 Interacerebroventricular infusions 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ahima R, Harlan R (1990) Charting of type II glucoreceptor-like immunoreactivity in the rat central nervous system. Neuroscience 39: 579–604PubMedCrossRefGoogle Scholar
  2. Ahima R, Krozowski Z, Harlan R (1991) Type I corticosteroid receptor-like immunoreactivity in the rat CNS: distribution and regulation by corticosteroids. J Comp Neurol 313: 522–538PubMedCrossRefGoogle Scholar
  3. Cintra M, Bhatnagar G, Chadi B, Tinner B, Lindberg J, Gustafsson J-Å., Agnati LF, Fuxe K (1994) Glial and neuronal glucocorticoid receptor immunoreactive cell populations in developing, adult, and aging brain. Ann NY Acad Sci 746: 42–61PubMedCrossRefGoogle Scholar
  4. Fahlke C, Engel JA, Eriksson CJP, Hård E, Söderpalm B (1994a) Involvement of corticosterone in the modulation of ethanol consumption in the rat. Alcohol 11: 195–202PubMedCrossRefGoogle Scholar
  5. Fahlke C, Hård E, Thomasson R, Engel JA, Hansen S (1994b) Metyrapone-induced suppression of corticosterone synthesis reduces ethanol consumption in high-preferring rats. Pharmacol Biochem Behav 48: 977–981PubMedCrossRefGoogle Scholar
  6. Fahlke C, Hård E, Eriksson CPJ, Engel JA, Hansen S (1995) Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomized rat, and the effect of type I and type II corticosterone receptor antagonists. Psychopharmacology 117: 216–224PubMedCrossRefGoogle Scholar
  7. Ganong WF (1987) Review of medical physiology., Appleton & Lange, NorwalkGoogle Scholar
  8. Green PK, Wilkinson CW, Woods SC (1992) Intraventricular corticosterone increases the rate of body weight gain in under-weight adrenalectomized rats. Endocrinology 130: 269–275PubMedCrossRefGoogle Scholar
  9. Hansen S, Fahlke C, Hård E, Engel JA (1994) Adrenal corticosteroids modulate the consumption of ethanol in the rat. In: Palomo T, Archer T (eds) Strategies for studying brain disorders: depressive, anxiety and abuse disorders. Farand, Press, London, pp 465–479Google Scholar
  10. Hansen S, Fahlke C, Söderpalm AHV, Hård E (1995) Significance of adrenal corticosteroid secretion for the food restriction-induced enhancement of ethanol drinking in the rat. Psychopharmacology 121: 213–221PubMedCrossRefGoogle Scholar
  11. Hårfstrand A, Fuxe K, Cintra A, Agnati LF, Zini I, Wikström A-C, Okret S, Yu Z-Y, Goldstein M, Steinbusch H, Verhofstad A, Gustafsson J-Å (1986) Glucocorticoid receptor immunore-activity in monoaminergic neurons of rat brain. Proc Natl Acad Sci USA 83: 9779–9783PubMedCrossRefGoogle Scholar
  12. Hyytiä, P, Koob GF (1995) GABAA receptor antagonism in the extended amygdala decreases ethanol self-administration in rats. Eur J Pharm 283: 151–159CrossRefGoogle Scholar
  13. Joëls M, de Kloet ER (1992) Control of neuronal excitability by corticosteroid hormones. Trends Neural Sci 15: 25–30CrossRefGoogle Scholar
  14. Korte SM, De Boer SF, De Kloet ER, Bohus B (1995) Anxiolytic-like effects of selective mineralocorticoid and glucocorticoid antagonists on fear-enhanced behavior in the elevated plusmaze. Psychoneuroendocrinology 20: 385–394PubMedCrossRefGoogle Scholar
  15. MacLennan AJ, Drugan RC, Hyson RL, Maier SF, Madden JD, Barchas JD (1982) Corticosterone: a critical factor in an opioid form of stress-induced analgesia. Science 215: 1530–1532PubMedCrossRefGoogle Scholar
  16. Majewska MD, Bisserbe J-C, Eskay RL (1985) Glucocorticoids are modulators of GABAA receptors in brain. Brain Res 339: 178–182PubMedCrossRefGoogle Scholar
  17. Marinelli M, Piazza PV, Barrot M, Rougé-Pont F, Kharoby M, Le Moal M, Simon H (1994) Glucocorticoids and drug abuse: influences of acute inhibition of corticosterone synthesis and administration of corticosteroid receptor antagonists on cocaine-induced locomotion. Soc Neurosci Abstr 20: 666.6Google Scholar
  18. McEwen BS (1991) Non-genomic and genomic effects of steroids on neural activity. Trends Pharmacol Sci. 12: 141–147PubMedCrossRefGoogle Scholar
  19. Mendelson SD, McEwen BS (1992) Autoradiographic analyses of the effects of adrenalectomy and corticosterone on 5-HT1A and 1B receptors in the dorsal hippocampus and cortex of the rat. Neuroendocrinol 55: 444–50Google Scholar
  20. Moguilewsky M, Raynaud JR (1980) Evidence for a specific mineralocorticoid receptor in rat pituitary and brain. J Steroid Biochem 12: 309–314PubMedCrossRefGoogle Scholar
  21. Moore FL, Orchinik M (1991) Multiple molecular actions for steroids in teh regulation of reproductive behaviors. Semin Neurosci 3: 489–496CrossRefGoogle Scholar
  22. Nevo I, Hamon M (1995) Neurotransmitter and neuromodulatory mechanisms involved in alcohol abuse and alcoholism. Neurochem Int 26: 305–336PubMedCrossRefGoogle Scholar
  23. Orchinik M, Moore FL, Rose JD (1994) Mechanistic and functional studies of rapid corticosteroid actions. Ann NY Acad Sci 746: 101–112PubMedCrossRefGoogle Scholar
  24. Philibert D, Moguilewski M, Mary I, Lecaque D, Tornemine C, Secchi C, Deraedt R (1985) Pharmacological profile of RU 486 in animals. In: Baulieu EE, Segal SH (eds) The antiprogestin steroid RU 486 and human fertility control. Plenum. New York. pp 49–68Google Scholar
  25. Piazza PV, Deminière J-M, le Moal M, Simon H (1990) Stress-and pharmacologically-induced behavioral sensitization increases vulnerability to acquisition of amphetamine selfadministration. Brain Res 514: 22–26.PubMedCrossRefGoogle Scholar
  26. Piazza PV, Maccari S, Deminière J-M Le Moal M, Mormède P, Simon H (1991) Corticosterone levels determine individual vulnerability to amphetamine self-administration. Proc Natl Acad Sci USA 88: 2088–2092PubMedCrossRefGoogle Scholar
  27. Piazza PV, Deroche V, Rougé-Pont F, Deminière JM, Maccari S, Le Moal M, Simon H (1992) Individual differences in the sensitivity to corticosterone’s reinforcing effets and in corticosterone-induced dopamine release may be a biological, basis for sensation-seeking. Soc Neurosci Abstr 449: 13Google Scholar
  28. Prasad C, Prasad A (1995) A relationship betwwen increased voluntary alcohol preference and basal hypercorticosteronemia associated with an attenuated rise in corticosterone output during stress. Alcohol 12: 59–63PubMedCrossRefGoogle Scholar
  29. Ratka A, Sutanto W, Bloemers M, de Kloet ER (1989) On the role of brain, mineralocorticoid (type I) and glucocorticoid (type II) receptors in neuroendocrine regulation. Neuroendocrinology 50: 117–123PubMedGoogle Scholar
  30. Sutanto W, De Kloet ER (1995) Corticosteroid receptor antagonists: a current perspective. Pharm, World Sci 17: 31–41CrossRefGoogle Scholar
  31. Sutanto W, Handelmann G, De Bree F, De Kloet ER (1989) Multifaceted, interaction of corticosteroids with the intracellular receptors and with membrane GABAA receptor complex in the rat brain. J Neuroendocrinol 4 243–247CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • C. Fahlke
    • 1
  • E. H»rd
    • 1
  • S. Hansen
    • 1
  1. 1.Department of PsychologyGöteborg UniversityGöteborgSweden

Personalised recommendations