Serotonergic Mechanisms in Alcohol Intake

  • David T. Wong
  • James M. Murphy
Part of the Experimental Biology and Medicine book series (EBAM, volume 21)


Based primarily on animal studies, pharmacological manipulation of brain serotonin (5-hydroxytryptamine, 5HT) neurons has become recognized recently as a potentially important therapeutic approach for the treatment of alcoholism (1,13,38). Two general lines of evidence have implied an inverse relationship between the functioning of the brain 5HT neurotransmitter systems and alcohol drinking behavior: (a) Pharmacological manipulations that increase 5HT functioning cause a reversal of the preference for ethanol and a decrease in alcohol consumption (14,29), and (b) rats and mice that exhibit a high preference for alcohol have a lower content of 5HT and 5-hydroxindoleacetic acid (5HIAA), the primary 5HT metabolite, in several brain regions compared with alcohol-non-preferring animals (28,50 and Lumeng, this volume). In agreement with these findings, some pharmacological manipulations shown to be effective in animal studies have been tested and proven efficacious in decreasing alcohol consumption in humans (1,13,14,36,37), and it has been observed that patients with a history of alcoholism have a lower content of 5HIAA in cerebrospinal fluid (3), lower blood and platelet content of 5HT (4) and a decreased uptake of 5HT into platelets (22).


Alcohol Intake Uptake Inhibitor Pharmacological Manipulation Reduce Alcohol Consumption Serotonergic Mechanism 
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  1. 1.
    Amit, Z., Brown, S., Sutherland, A., Rockman, G., Gill, K. and Selvaggi, N. (1985) in: Research Advances in New Psychopharmacological Treatments for Alcoholism (Naranjo, C.A. and Sellero, E.M., eds.), Ercerpta Medica, Amersterdam, pp. 189–198.Google Scholar
  2. 2.
    Amit, Z., Sutherland, E.A., Gill, K. Ogren, S-O. (1984) Neurosci. Biobehav. Rev. 8, 35–54.PubMedCrossRefGoogle Scholar
  3. 3.
    Ballenger, J.C., Goodwin, F.K., Major, L.F. and Brown, G.L. (1979) Arch. Gen. Psychiat. 36, 224–227.PubMedGoogle Scholar
  4. 4.
    Banki, C.M. (1978) Acta. psychiat. Scand. 57, 232–238.PubMedCrossRefGoogle Scholar
  5. 5.
    Bymaster, F.P., Wong, D.T., Lumeng, L. and Li, T-L. (1986) Soc. Neurosci. Abstr. 12, 1235.Google Scholar
  6. 6.
    Collins, D.M. and Myers, R.D. (1987) Alcohol 4, 49–56.PubMedCrossRefGoogle Scholar
  7. 7.
    Daoust, M., Chretien, P., Moore, N., Saligaut, C., Lhuintre, J.P. and Boismare, F. (1985) Pharmacol. Biochem. Behav. 22, 205–208.PubMedCrossRefGoogle Scholar
  8. 8.
    Dourish, C.T., Hutson, P.H., Kennett, G.A. and Curzon, G. (1986) Appetite 7 (Suppl.), 127–140.PubMedGoogle Scholar
  9. 9.
    Frey, H.H., Magnussen, M.P. and Kaergaard-Nielsen, C. (1970) Arch. Int. Pharmacodyn. Ther. 183, 165–172.PubMedGoogle Scholar
  10. 10.
    Fuller, R.W. and Wong, D.T. (1987) J. Clin. Phychopharmacol. 7 (Suppl. 6) 36–43.Google Scholar
  11. 11.
    Fuller, R.W. and Wong, D.T. (1988) Drug Dev. Res., in press.Google Scholar
  12. 12.
    Gaddum, J.H. and Picarelli, Z.P. (1957) J. Pharmacol. 12, 323–328.Google Scholar
  13. 13.
    Gorelick, D.A. (1986) Alcoholism: Clin. Exp. Res. 10, 13.CrossRefGoogle Scholar
  14. 14.
    Gorelick, D.A. (1988) In: Recent Developments in Alcoholism, Vol. 7 (Galantes, M., ed), in press.Google Scholar
  15. 15.
    Gozlan, H., Mestikawy, S.E., Pichat, L., Glowinski, J. and Hamon, M. (1983) Nature 305, 140–142.PubMedCrossRefGoogle Scholar
  16. 16.
    Hall, H. and Ogren, S.O. (1981) Eur. J. Pharmacol. 70, 393–407.PubMedCrossRefGoogle Scholar
  17. 17.
    Heuring, R.E. and Peroutka, S.J. (1987) J. Neurosci. 7, 894–903.PubMedGoogle Scholar
  18. 18.
    Hill, S.Y. (1974) Biol. Psychiatry 8, 151–158.PubMedGoogle Scholar
  19. 19.
    Hoyer, D. (1988) TIPS Reviews 9, 89–94.Google Scholar
  20. 20.
    Hoyer, D., Engel, G. and Kalkman, H.O. (1985) Eur. J. Pharmacol. 118, 13–23.PubMedCrossRefGoogle Scholar
  21. 21.
    Hyttel, J. (1982) Prog. Neuropsychopharmacol. Biol. Psychiat. 6, 275–276.CrossRefGoogle Scholar
  22. 22.
    Kent, I.A., Campbell, J.L., Pazdernik, T.L., Hunter, R., Gunn, W.H. and Goodwin, D.W. (1985) J. Studies Alcohol 46, 357–359.Google Scholar
  23. 23.
    Kilpatrick, G.J., Jones, B.J. and Tyers, M.B. (1987) Nature 330, 747–748.CrossRefGoogle Scholar
  24. 24.
    Krasner, N., Dow, J., Moore, M.R., Thompson, G.G. and Goldberg, A. (1975) Postgrad. Med. J. 51 (Suppl. 1), 76–79.PubMedGoogle Scholar
  25. 25.
    Lawrin, M.O., Naranjo, C.A. and Sellers, E.M. (1985) Proc. Can. Fed. Biol. Soc. 28, 81.Google Scholar
  26. 26.
    LeBourhis, B., Uzan, A., Aufrer, G. (1981) Ann. Pharm. Fr. 39, 11–20.Google Scholar
  27. 27.
    Lemberger, L, Fuller, R.W. and Zerbe, R.L. (1985) Clin. Neuropharmacol. 8, 299–317.PubMedCrossRefGoogle Scholar
  28. 28.
    Li, T-K., Lumeng, L., McBride, W.J. and Murphy, J.M. (1987) Alcohol and Alcoholism, Suppl 1, 91–96.Google Scholar
  29. 29.
    McBride, W.J., Murphy, J.M., Lumeng, L. and Li, T-K. (1988) In: Recent Developments in Alcoholism, Vol. 7 Plenum Press, in press.Google Scholar
  30. 30.
    McBride, W.J., Murphy, J.M., Lumeng, L. and Li, T-K (1988) Pharmacol. Biochem. Behav. 30, 1045–1050.PubMedCrossRefGoogle Scholar
  31. 31.
    Middlemiss, D.N., Hibert, M. and Fozard, J.R. (1986) Ann. Rep. Medicinal Chem. 21, 41–50.CrossRefGoogle Scholar
  32. 32.
    Miksic, S.L., Barry, H. and Krimmer, E.C. (1982) Alcohol Clin. Exp. Res. 6, 149.Google Scholar
  33. 33.
    Murphy, J.M., McBride, W.J., Lumeng, L. and Li, T-K. (1987) Alcoholism, Clin. Exp. Res. 11(2) 208.Google Scholar
  34. 34.
    Murphy, J.M., McBride, W.J., Lumeng, L. and Li, T-K. (1982) Pharmacol. Biochem. Behav. 16, 145–149.PubMedCrossRefGoogle Scholar
  35. 35.
    Murphy, J.M., Waller, M.B., Gatto, G.J., McBride, W.J., Lumeng, L. and Li, T-K. (1985) Alcohol 2, 349–352.PubMedCrossRefGoogle Scholar
  36. 36.
    Murphy, J.M., Waller, M.G., Gatto, G.J., McBride, W.J., Lumeng, L. and Li, T-K. (1988) Alcohol 5, 283–286.PubMedCrossRefGoogle Scholar
  37. 37.
    Naranjo, C.A., Sellers, E.M. and Lawrin, M.O. (1986) J. Clin. Psychiatry 47, 16–22.PubMedGoogle Scholar
  38. 38.
    Naranjo, C.A., Sellers, E.M., Roach, C.A., Woodley, D.V., Sanchez-Craig, M. and Sykora, K. (1984) Clin. Charmacol. Ther. 35, 374–381.CrossRefGoogle Scholar
  39. 39.
    Peroutka, S.J. and Snyder, S.H. (1979) Mol. Pharmacol. 16, 687–699.PubMedGoogle Scholar
  40. 40.
    Privette, T.H., Hornsby, R.L. and Myers, R.D. (1988) Alcohol 5, 147–152.PubMedCrossRefGoogle Scholar
  41. 41.
    Richelson, E. and Nelson, A. (1984) J. Pharmacol. Exp. Ther. 230, 94–102.PubMedGoogle Scholar
  42. 42.
    Rockman, G.E., Amit, Z., Brown, Z.W., Bourque, C. and Ogren, S-O. (1982) Neuropharmacology 21, 341–347.PubMedCrossRefGoogle Scholar
  43. 43.
    Rockman, G.E., Amit, Z., Carr, G., Brown, Z.W. and Ogren, S-O. (1979) Arch. Int. Pharmacodyn. 241, 145–159.Google Scholar
  44. 44.
    Smith, L.M. and Peroutka, S.J. (1986) Pharmacol. Biochem. Behav. 24, 1513–1519.PubMedCrossRefGoogle Scholar
  45. 45.
    Witkin, J.M., Mansbach, R.S., Barrett, J.E., Bolger, G.T., Skolnick, P. and Weissman, B. (1987) J. Pharmacol. Exp. Ther. 243, 970–977.PubMedGoogle Scholar
  46. 46.
    Wong, D.T., Bymaster, F.P., Horng, J.S. and Molloy, B.B. (1975) J. Pharmacol. Exp. Ther. 193, 804–811.PubMedGoogle Scholar
  47. 47.
    Wong, D.T., Bymaster, P.P., Reid, L.R. and Threlkeld, P.G. (1983) Biochem. Pharmacol. 7, 1287–1293.CrossRefGoogle Scholar
  48. 48.
    Wong, D.T. and Fuller, R.W. (1987) Obesity 11 (Suppl. 3), 125–133.Google Scholar
  49. 49.
    Wong, D.T., Lumeng, L., Threlkeld, P.G., Reid, L.R. and Li, T-K. (1988) J. Neural Trans. 71, 207–218.CrossRefGoogle Scholar
  50. 50.
    Yoshimoto, K. and Setsuo, K. (1987) Pharmacol. Biochem. Behav. 27, 317–322.PubMedCrossRefGoogle Scholar
  51. 51.
    Zabik, J.E., Binkerd, K. and Roache, J.D. (1985) in: Research Advances in New Psychopharmacological Teratmetns for Alcoholism, Naranjo, C.A. and Sellero, E.M. eds., pp. 87–105, Excerpta Medica, Amsterdam.Google Scholar
  52. 52.
    Zabik, J.E., Roache, J.D., Sidor, R. and Nash, J.F., Jr. (1982) Pharmacologist 24, 204.Google Scholar

Copyright information

© The Humana Press Inc. 1989

Authors and Affiliations

  • David T. Wong
    • 1
  • James M. Murphy
    • 2
  1. 1.Lilly Research LaboratoriesEli Lilly and Company Lilly Corporate CenterIndianapolisUSA
  2. 2.The Institute of Psychiatric ResearchIndiana University School of MedicineIndianapolisUSA

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