Alcoholism pp 175-181 | Cite as

The Neurochemistry of Ethanol Tolerance

  • Boris Tabakoff
  • Paula L. Hoffman
Part of the NATO ASI Series book series (NSSA, volume 206)

Abstract

Tolerance to ethanol (alcohol) or any other drug is defined as an acquired resistance to the physiological and/or behavioral effects of the drug. Another empirical definition of tolerance is that a given dose of drug has less effect in an individual on his/her later exposures to the drug than on the first exposure. The phenomenon of tolerance, as well as the mechanisms underlying its development, can be complex (Tabakoff et al., 1982), ranging from changes in drug disposition or metabolism (“metabolic tolerance”), to alterations in the function of cells including the neurons of the central nervous system which result in drug resistance. The cellular adaptations to resist a drug’s actions are part of the phenomenon of “functional” tolerance and the processes that contribute to functional tolerance will be the focus of this discussion.

Keywords

Dopamine Serotonin Polypeptide Arginine Norepinephrine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allan, A. M. and Harris, R. A., 1986, Gamma-aminobutyric acid and alcohol actions: Neurochemical studies of long sleep and short sleep mice, Life Sci., 39: 2005–2015.Google Scholar
  2. Allan, A. M. and Harris, R. A., 1987, Acute and chronic ethanol treatments alter GABA receptor operated chloride channels, Pharm. Biochem. Behay. 27:665–670.Google Scholar
  3. Cappell, H. and LeBlanc, A. E., 1979, Tolerance to, and physical dependence on, ethanol: Why do we study them? Drug Ale. Dependence 4:15–31.Google Scholar
  4. Curran, T., 1988, The fos oncogene, in: The Oncogene Handbook, E.P. Reddy, A.M. Skalka and T. Curran, eds., Elsevier Sciences Publishers B.V., Amsterdam.Google Scholar
  5. Dingledine, R., Myers, S. J. and Nicholas, R. A., 1990, Molecular biology of mammalian amino acid receptors, FASEB J. 4:2636–2645.Google Scholar
  6. Dolin, S. J. and Little, H. J., 1989, Are changes in neuronal calcium channels involved in ethanol tolerance? J. Pharmacol. Exp. Ther. 250:985–991.Google Scholar
  7. Frye, G. D. and Breese, G. R., 1982, GABAergic modulation of ethanol-induced motor impairment, J. Pharmacol. Exp. Ther. 223:750–756.Google Scholar
  8. Garrett, K. M., Saito, N., Duman, R. S., Abel, M. S., Ashton, R. A., Fujimori, S., Beer, B., Tallman, J. F., Vitek, M. P. and Blume, A. J., 1990, Differential expression of y-aminobutyric acidA receptor subunits, Mol. Pharmacol. 37:652–657.Google Scholar
  9. Greenberg, M. E., Ziff, E. B. and Greene, L. A., 1986, Stimulation of neuronal acetylcholine receptor induces rapid gene transcription, Science, 234:80–83.Google Scholar
  10. Hakkinen, J. M. and Kulonen E., 1976, Ethanol intoxication and gamma-aminobutyric acid, J.Neurochem. 27:631–633.Google Scholar
  11. Hoffman, P. L., Ritzmann, R. F., Walter, R. and Tabakoff, B., 1979, Arginine vasopressin maintains ethanol tolerance, Nature 276:614–616.Google Scholar
  12. Hoffman, P. L., Melchior, C. L. and Tabakoff, B., 1983, Vasopressin maintenance of ethanol tolerance requires intact brain noradrenergic systems, Life Sci. 32:1065–1071.Google Scholar
  13. Hoffman, P. L. and Tabakoff, B., 1985, Ethanol’s action on brain biochemistry, in: Alcohol and the Brain: Chronic Effects, R.E. Tarter and D.H. van Thiel, eds., Plenum Medical Book Company, New York.Google Scholar
  14. Hoffman, P. L., 1987, Central nervous system effects of neurohypophyseal peptides, in: The Peptides, C.W. Smith, ed., Academic Press, New York.Google Scholar
  15. Hoffman, P. L., Tabakoff, B., Szabó, G., Suzdak, P. D. and Paul, S. M., 1987, Effect of an imidazobenzodiazepine, Ro15–4513, on the incoordination and hypothermia produced by ethanol and pentobarbital, Life Sci. 41:611–619.Google Scholar
  16. Hosey, M. M. and Lazdunski, M., 1988, Calcium channels: Molecular pharmacology, structure and regulation, J. Membrane Biol. 104:81–105.Google Scholar
  17. Ishizawa, H., Tabakoff, B., Mefford, I. N. and Hoffman, P. L., 1990, Reduction of arginine vasopressin binding sites in mouse lateral septum by treatment with 6hydroxydopamine, Brain Res. 507:189–194.Google Scholar
  18. Jard, S., 1983, Vasopressin isoreceptors in mammals: Relation to cyclic AMP-dependent and cyclic AMP-independent transduction mechanisms, Current Topics Membr. Transp. 18:255–285.Google Scholar
  19. Lê, A. D., Khanna, J. M., Kalant, H. and LeBlanc, A. E., 1981, Effect of modification of brain serotonin (5-HT), norepinephrine (NE) and dopamine (DA) on ethanol tolerance, Psychopharmacol. 75:231–235.Google Scholar
  20. Lê, A. D., Khanna, J. M., Kalant, H. and LeBlanc, A. E., 1981, The effect of lesions in the dorsal, median and magnus raphe nuclei on the development of tolerance to ethanol, J. Pharmacol. Exp. Ther. 218:525–529.Google Scholar
  21. Lê, A.D., Kalant, H. and Khanna, J.M. (1982) Interaction between des-glycinami9[Arg8]vasopressin and serotonin on ethanol tolerance. Eur. J. Pharmacol. 80:337–345.Google Scholar
  22. Liljequist, S., Culp, S. and Tabakoff, B., 1986, Effect of ethanol on the binding of [35S]-tbutylbicyclophosphorothionate to mouse brain membranes, Life Sci. 38:1931–1939.Google Scholar
  23. Lüddens, H., Pritchett, D. B., Köhler, M., Killisch, I., Keinänen, K., Monyer, H., Sprengel, R. and Seeburg, P. H., 1990, Cerebellar GABAA receptor selective for a behavioral alcohol antagonist, Nature 346:648–651.Google Scholar
  24. Melchior, C. L. and Tabakoff, B., 1981, Modification of environmentally cued tolerance to ethanol in mice, J. Pharmacol. Exp. Ther. 219:175–180.Google Scholar
  25. Melchior, C. L., Hoffman, P. L. and Tabakoff, B., 1983, Influencing environment-dependent tolerance to ethanol, in: Ethanol Tolerance and Dependence: Endocrinological Aspects (National Research Monograph No. 13), T.J. Cicero, ed., U.S. Government Printing Office, Washington, D.C.Google Scholar
  26. Morrow, A. L., Suzdak, P. D., Karanian, J. W. and Paul, S. M., 1988, Chronic ethanol administration alters y-aminobutyric acid, pentobarbital and ethanol-mediated 36C1uptake in cerebral cortical synaptoneurosomes, J. Pharmacol. Exp. Ther. 246:158–164.Google Scholar
  27. Morrow, A. L., Montpied, P., Lingford-Hughes, A. and Paul, S. M., 1990, Chronic ethanol and pentobarbital administration in the rat: Effects on GABAA receptor function and expression in brain, Alcohol, 7:237–244.Google Scholar
  28. Numan, R., 1981, Multiple exposures to ethanol facilitates intravenous self-administration of ethanol by rats, Pharm. Biochem. Behay. 15:101–108.Google Scholar
  29. Rastogi, S. K., Thyagarajan, R., Clothier, J. and Ticku, M. K., 1986, Effect of chronic treatment of ethanol on benzodiazepine and picrotoxin sites on the GABA receptor complex in regions of the brain of the rat, Neuropharmacol. 26:1179–1184.Google Scholar
  30. Rathna Giri, P., Dave, J. R., Tabakoff, B. and Hoffman, P. L., 1990, Arginine vasopressin induces the expression of c-fos in the mouse septum and hippocampus, Mol. Brain Res. 7:131–137.Google Scholar
  31. Saito, T., Lee, J. M. and Tabakoff, B., 1985, Ethanol’s effects on cortical adenylate cyclase activity, J. Neurochem. 44:1037–1044.Google Scholar
  32. Skolnick, P. and Paul, S. M., 1982, Benzodiazepine receptors in the central nervous system, Int. Rev. Neurobiol. 23:103–140.Google Scholar
  33. Speisky, M. B. and Kalant, H., 1985, Site of interaction, of serotonin and desglycinamidearginine-vasopressin in maintenance of ethanol tolerance, Brain Res. 326:281–290.Google Scholar
  34. Squire, L. R. and Davis, H. P., 1981, The pharmacology of memory: A neurobiological perspective, Ann. Rev. Pharmacol. Toxicol. 21:323–356.Google Scholar
  35. Suzdak, P. D., Schwartz, R. D., Skolnick, P. and Paul, S. M., 1986, Ethanol stimulates y-aminobutyric acid receptor mediated chloride transport in rat brain synaptoneurosomes, Proc. Natl. Acad. Sci. USA 83:4071–4075.Google Scholar
  36. Suzdak, P. D., Glowa, J. R., Crawley, J. N., Schwartz, R. D., Skolnick, P. and Paul, S. M., 1986, A selective imida7obenzodiazepine antagonist of ethanol in the rat, Science 234:1243–1247.Google Scholar
  37. Szabo, G., Hoffman, P. L. and Tabakoff, B., 1988, Forskolin promotes the development of ethanol tolerance in 6-hydroxydopamine-treated mice, Life Sci. 42:615–621.Google Scholar
  38. Szabd, G., Tabakoff, B. and Hoffman, P. L., 1988, Receptors with V1 characteristics mediate the maintenance of ethanol tolerance by vasopressin, J. Pharmacol. Exp. Ther. 247:536–541.Google Scholar
  39. Tabakoff, B. and Ritzmann, R. F., 1977, The effects of 6-hydroxydopamine on tolerance to and dependence on ethanol, J. Pharmacol. Exp. Ther. 203:319–331.Google Scholar
  40. Tabakoff, B., Melchior, C. L. and Hoffman, P. L., 1982, Commentary on ethanol tolerance, Alcoholism: Clin. Exp. Res. 6:252–259.CrossRefGoogle Scholar
  41. Tabakoff, B. and Hoffman, P. L., 1989, Adaptive responses to ethanol in the central nervous system, in: Alcoholism: Biomedical and Genetic Aspects, H.W. Goedde and D.P. Agarawal, eds., Pergamon Press, New York.Google Scholar
  42. Tanaka, M., de Kloet, E. R., de Wied, D. and Versteeg, D. H. G., 1977, Argininevasopressin affects catecholamine metabolism in specific brain nuclei, Life Sci. 20:1799–1808.Google Scholar
  43. Trzaskowska, E., Pucilowski, O., Dyr, W., Kostowski, W. and Hauptmann, M., 1986, Suppression of ethanol tolerance and dependence in rats treated with DSP-4, a noradrenergic neurotoxin, Drug Alc. Dependence 18:349–353.Google Scholar
  44. Waller, M. B., McBride, W. J., Lumeng, L. and Li, T-K., 1983, Initial sensitivity and acute tolerance to ethanol in the P and NP lines of rats, Pharm. Biochem. Behay. 19:683–686.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Boris Tabakoff
    • 1
    • 2
  • Paula L. Hoffman
    • 1
    • 2
  1. 1.Department of PharmacologyUniv. of Colorado Hlth. Sci. Ctr.DenverUSA
  2. 2.Division of Intramural Clinical and Biological ResearchNational Institute on Alcohol Abuse and AlcoholismRockvilleUSA

Personalised recommendations