Ethanol’s Action on Brain Biochemistry

  • Paula L. Hoffman
  • Boris Tabakoff


It is generally assumed that ethanol exerts its effects in the central nervous system (CNS) by perturbing the normal processes of information conduction and transmission. Using electrophysiologic techniques, one can directly assess the effects of ethanol on neuronal activity, and such studies have been performed (e.g., see reference 1). However, insights into the molecular mechanisms by which ethanol affects neuronal activity have, at present, been derived primarily from neurochemical assessments of ethanol’s actions. In the CNS, as in the peripheral nervous system, rates of neurotransmitter metabolism usually reflect the level of neuronal activity,2,3 and one can assess responses to ethanol by determining ethanol’s effect on neurotransmitter synthesis, release, and metabolism and/or by measuring the interactions of neurotransmitters with specific receptors in the presence of ethanol. The results of such studies provide the basis for this review.


Adenylate Cyclase Chronic Ethanol Opiate Receptor Ethanol Tolerance Choline Uptake 
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  1. 1.
    Kalant H, Woo N: Electrophysiological effects of ethanol on the nervous system. Pharmacol Ther 14: 431–457, 1981PubMedCrossRefGoogle Scholar
  2. 2.
    Aghajanian GK, Bunney BS, Kuhar Mk Use of single unit recording in correlating transmitter turnover with impulse flow in monoamine neurons, in Mandel Ai (ed): New Concepts in Neurotransmitter Regulation. New York, Plenum Press, 1973, p 115CrossRefGoogle Scholar
  3. 3.
    Herr BE, Gallagher DW, Roth RH: Tryptophan hydroxylase: Activation in vivo following stimulation of central serotonergic neurons. Biochem Pharmacol 24: 2019–2023, 1975PubMedCrossRefGoogle Scholar
  4. 4.
    Karper C: Neuropathology of brain damage caused by alcohol. Med J Aust 2: 277–282, 1982Google Scholar
  5. 5.
    Riley JN, Walker DW: Morphological alterations in hippocampus after long-term alcohol consumption in mice. Science 201: 646–648, 1978PubMedCrossRefGoogle Scholar
  6. 6.
    Golden CJ, Graber B, Blose, 1, et al: Difference in brain densities between chronic alcoholic and normal control patients. Science 211: 508–510, 1981PubMedCrossRefGoogle Scholar
  7. 7.
    Tabakoff B, Melchior CL, Hoffman PL: Commentary on ethanol tolerance. Alcoholism: Clin Exp Res 6: 252–259, 1982CrossRefGoogle Scholar
  8. 8.
    Jaffe JH: Drug addiction and drug abuse, in Goodman LS, Gilman A (eds): The Pharmacological Basis of Therapeutics, ed 5. New York, Macmillan Co, 1970, p 284Google Scholar
  9. 9.
    Tabakoff B, Ritzmann RF: The effects of 6-hydroxydopamine on tolerance to and dependence on ethanol. J Pharmacol Exp Ther 203: 319–331, 1977PubMedGoogle Scholar
  10. 10.
    Tabakoff B, Rothstein JD: The biology of tolerance and dependence, in Tabakoff B, Sutker PB, Randall CL (eds): Medical and Social Aspects of Alcohol Abuse. New York, Plenum Press, 1983, p 187CrossRefGoogle Scholar
  11. 11.
    Israel Y, Kalant H, LeBlanc AE: Effect of lower alcohols on potassium transport and microsomal adenosine triphosphatase activity of rat cerebral cortex. Biochem J 100: 27–33, 1966Google Scholar
  12. 12.
    Sun AY, Samorajski T: Effects of ethanol on the activity of adenosine triphosphatase and acetylcholinesterase in synaptosomes isolated from guinea pig brain. J Neurochem 17: 1365–1372, 1970PubMedCrossRefGoogle Scholar
  13. 13.
    Tabakoff B: Inhibition of sodium, potassium and magnesium-activated ATP ases by acetaldehyde and biogenic aldehydes. Res Commun Chem Pathol Pharmacol 7: 621–624, 1974PubMedGoogle Scholar
  14. 14.
    Westcott JY, Weiner H: Effect of ethanol on synaptosomal (Na+-K+)ATPase in control and ethanol-dependent rats. Arch Biochem Biophys 223: 51–57, 1983PubMedCrossRefGoogle Scholar
  15. 15.
    Rangaraj N, Kalant H: Interaction of ethanol and catecholamines on rat brain (Na +-K+)ATPase. Can J Physiol Pharmacol 57: 1098–1106, 1979PubMedCrossRefGoogle Scholar
  16. 16.
    Israel Y, Kalant H, LeBlanc AE, et al: Changes in cation transport and (Na+-K+)-activated adenosine triphosphatase produced by chronic administration of ethanol. J Pharmacol Exp Ther 174: 330–336, 1970PubMedGoogle Scholar
  17. 17.
    Knox WH, Perrin GR, Sen AK: Effect of chronic administration of ethanol on (Na +-K+)-activated ATPase activity in six areas of the cat brain. J Neurochem 19: 2881–2884, 1972PubMedCrossRefGoogle Scholar
  18. 18.
    Guerri C, Grisolia S: Effects of prenatal and postnatal exposure of rats to alcohol: Changes in (Na+-K+)ATPase. Pharmacol Biochem Behav 17: 927–932, 1982PubMedCrossRefGoogle Scholar
  19. 19.
    Goldstein DB, Israel Y: Effects of ethanol on mouse brain (Na+-K+)-activated adenosine triphosphatase. Life Sci (Part II ) 2: 957–963, 1972Google Scholar
  20. 20.
    Akera T, Rech RH, Marquis TT, et al: Lack of relationship between brain (Na + + K+)-activated adenosine triphosphatase and the development of tolerance to ethanol in rats. J Pharmacol Exp Ther 185: 594–601, 1973PubMedGoogle Scholar
  21. 21.
    Rangaraj N, Kalant H: Effects of ethanol withdrawal, stress and amphetamine on rat brain (Na +-K+)ATPase. Biochem Pharmacol 27: 1139–1144, 1978PubMedCrossRefGoogle Scholar
  22. 22.
    Desaiah D, Ho IK: Kinetics of catecholamine-sensitive (Nat -K+)ATPase activity in mouse brain synaptosomes. Biochem Pharmacol 26: 2029–2035, 1977PubMedCrossRefGoogle Scholar
  23. 23.
    Levental M, Tabakoff, B: Sodium-potassium-activated adenosine triphosphatase activity as a measure of neuronal membrane characteristics in ethanol-tolerant mice. J Pharmacol Exp Ther 212: 315–319, 1980PubMedGoogle Scholar
  24. 24.
    Rangaraj N, Kalant H: Effect of chronic ethanol treatment on temperature dependence and on norepinephrine sensitization of rat brain (Nat -K+) adenosine triphosphatase. J Pharmacol Exp Ther 223: 536–539, 1982PubMedGoogle Scholar
  25. 25.
    Rangaraj N, Kalant H: Effect of chronic ethanol treatment on temperature dependence and on norepinephrine sensitization of rat brain (Nat + K+) adenosine triphosphatase. J Pharmacol Exp Ther 223: 536–539, 1982PubMedGoogle Scholar
  26. 26.
    Ross DH, Medina MA, Cardenas HL: Morphine and ethanol: Selective depletion of regional brain calcium. Science 186: 63–65, 1974PubMedCrossRefGoogle Scholar
  27. 27.
    Ross DH: Adaptive changes in Ca“-membrane interactions following chronic ethanol exposure. Adv Exp Med Biol 85A: 459–471, 1977Google Scholar
  28. 28.
    Ross DH, Kibler BC, Cardenas HL: Modification of glycoprotein residues as Ca++ receptor sites after chronic ethanol exposure. Drug Alcohol Depend 2: 305–315, 1977PubMedCrossRefGoogle Scholar
  29. 29.
    Michaelis EK, Myers SL: Calcium binding to brain synaptosomes. Biochem Pharmacol 28: 2081–2087, 1979PubMedCrossRefGoogle Scholar
  30. 30.
    Harris RA, Hood WF: Inhibition of synaptosomal calcium uptake by ethanol. J Pharmacol Exp Ther 213: 562–568, 1980PubMedGoogle Scholar
  31. 31.
    Stokes JA, Harris RA: Alcohols and synaptosomal calcium transport. Mol Pharmacol 22: 99–104, 1982PubMedGoogle Scholar
  32. 32.
    Friedman MB, Erickson CD, Leslie SW: Effects of acute and chronic ethanol administration on whole mouse brain synaptosomal calcium influx. Biochem Pharmacol 29: 1903–1908, 1980PubMedCrossRefGoogle Scholar
  33. 33.
    Nachsen DA, Blaustein MP: Some properties of potassium-stimulated calcium influx in pre-synaptic nerve endings. J Gen Physiol 76: 709–729, 1980CrossRefGoogle Scholar
  34. 34.
    Michaelis ML, Michaelis EK: Alcohol and local anesthetic effects on Na +-dependent Ca ++ fluxes in brain synaptic membrane vesicles. Biochem Pharmacol 32: 963–969, 1983PubMedCrossRefGoogle Scholar
  35. 35.
    Michaelis ML, Michaelis EK, Tehan T: Alcohol effects on synaptic membrane calcium ion fluxes. Pharmacol Biochem Behav 18 (Suppl 1): 19–23, 1983PubMedCrossRefGoogle Scholar
  36. 36.
    Carlen PL, Gurevich N, Durand D: Ethanol in low doses augments calcium-mediated mechanisms measured intracellularly in hippocampal neurons. Science 215: 306–309, 1982PubMedCrossRefGoogle Scholar
  37. 37.
    Yamamoto HA, Harris RA: Calcium-dependent 86Rb efflux and ethanol intoxication: Studies of human red blood cells and rodent brain synaptosomes. Eur J Pharmacol 88: 357–363, 1983PubMedCrossRefGoogle Scholar
  38. 38.
    Harris RA: Ethanol and pentobarbital inhibition of intrasynaptosomal sequestration of calcium. Biochem Pharmacol 30: 3209–3215, 1981PubMedCrossRefGoogle Scholar
  39. 39.
    Erickson CK, Tyler TD: Ethanol: Modification of acute intoxication by divalent cations. Science 199: 1219–1221, 1978PubMedCrossRefGoogle Scholar
  40. 40.
    Harris RA: Alteration of alcohol effects by calcium and other inorganic cations. Pharmacol Biochem Behav 10: 527–534, 1979PubMedCrossRefGoogle Scholar
  41. 41.
    Tabakoff B, Hoffman PL: Neurochemical aspects of tolerance to and physical dependence on alcohol, in Kissin B, Begleiter H (eds): The Biology of Alcoholism, vol 7. New York, Plenum Press, 1983, p 199CrossRefGoogle Scholar
  42. 42.
    Pohorecky LA: Biphasic action of ethanol. Biobehav Rev 1: 231–240, 1977.CrossRefGoogle Scholar
  43. 43.
    Towle AC, Sze PY: Chronic ethanol reduces brain calmodulin levels. Trans Am Soc Neurochem 12: 88, 1981Google Scholar
  44. 44.
    Luthin GR, Tabakoff B: Effects of ethanol on calmodulin levels in mouse striatum and cerebral cortex. Alcoholism: Clin Exp Res 8: 68–72, 1984Google Scholar
  45. 45.
    Tabakoff B, Hoffman PL: Alcohol and neurotransmitters, in Rigter H, Crabbe JC Jr (eds): Alcohol Tolerance and Dependence. Amsterdam, ElsevierfNorth-Holland Biomedical Press, 1980, p 201Google Scholar
  46. 46.
    Bacopoulos NG, Bhatanger RK, van Orden LS III: The effects of subhypnotic doses of ethanol on regional catecholamine turnover. J Pharmacol Exp Ther 204: 1–10, 1978PubMedGoogle Scholar
  47. 47.
    Hunt WA, Majchrowicz E: Alterations in the turnover of brain norepinephrine and dopamine in the alcohol-dependent rat. J Neurochem 23: 549–552, 1974CrossRefGoogle Scholar
  48. 48.
    Aston-Jones G, Foote SL, Bloom FE: Low doses of ethanol disrupt sensory responses of brain noradrenergic neurons. Nature (London) 296: 857–860, 1982CrossRefGoogle Scholar
  49. 49.
    Pohorecky LA, Brick J: Activity of neurons in the locus coeruleus of the rat: Inhibition by ethanol. Brain Res 131: 174–179, 1977PubMedCrossRefGoogle Scholar
  50. 50.
    Strahlendorf JC, Strahlendorf HK: Response of locus coeruleus neurons to direct application of ethanol. Neurosci Abstr 7: 312, 1982Google Scholar
  51. 51.
    Shefner SA, Tabakoff B: Basal firing rate of rat locus coerulus neurons affects sensitivity to ethanol. Alcohol,in pressGoogle Scholar
  52. 52.
    DeTurck KH, Vogel WH: Effects of acute ethanol on plasma and brain catecholamine levels in stressed and unstressed rats: Evidence for an ethanol-stress interaction. J Pharmacol Exp Ther 223: 348–354, 1982PubMedGoogle Scholar
  53. 53.
    Pohorecky LA: Effects of ethanol on central and peripheral noradrenergic neurons. J Pharmacol Exp Ther 189: 380–391, 1974PubMedGoogle Scholar
  54. 54.
    Borg S, Kvande H, Mossberg D, et al: Central nervous system noradrenaline metabolism and alcohol consumption in man. Pharmacol Biochem Behav 18 (Suppl 1): 375–378, 1983PubMedCrossRefGoogle Scholar
  55. 55.
    Borg S, Kvande H, Sedvall G: Central norepinephrine metabolism during alcohol intoxication in addicts and healthy volunteers. Science 213: 1135–1137, 1983CrossRefGoogle Scholar
  56. 56.
    Borg S, Czarnecka A, Kvande H, et al: Clinical conditions and concentrations of MOPEG in the cerebrospinal fluid and urine in male alcoholic patients during withdrawal. Alcoholism: Clin Exp Res 7: 411–415, 1983CrossRefGoogle Scholar
  57. 57.
    Davis VE, Brown H, Hoff JA, et al: Ethanol-induced alterations of norepinephrine metabolism in man. J Lab Clin Med 69: 787–799, 1967PubMedGoogle Scholar
  58. 58.
    Wolfe BB, Harden TK, Molinoff PB: In vitro study of beta-adrenergic receptors. Annu Rev Pharmacol Toxicol 17: 575–604, 1977PubMedCrossRefGoogle Scholar
  59. 59.
    Sporn JR Harden RK, Wolfe BB, et al.: Beta-adrenergic receptor involvement in 6-hydroxydopamine-induced supersensitivity in rat cerebral cortex. Science 194:624–625, 1976Google Scholar
  60. 60.
    Minneman KP, Dibner MD, Wolfe BB, et al: 131 and ß2-adrenergic receptors in rat cerebral cortex are independently regulated. Science 204: 866–868, 1979PubMedCrossRefGoogle Scholar
  61. 61.
    Chin JH, Goldstein DB: Effects of low concentrations of ethanol on the fluidity of spin-labeled erythrocyte and brain membranes. Mol Pharmacol 13: 435–441, 1977PubMedGoogle Scholar
  62. 62.
    Rodbell M: The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature 284: 17–22, 1980PubMedCrossRefGoogle Scholar
  63. 63.
    French SW, Palmer DS, Narod NE, et al: Noradrenergic sensitivity of the cerebral cortex after chronic ethanol ingestion and withdrawal. J Pharmacol Exp Ther 194: 319–326, 1975PubMedGoogle Scholar
  64. 64.
    Banerjee SV, Sharma VK, Khanna JM: Alterations in beta-adrenergic receptor binding during ethanol withdrawal. Nature 276: 407–409, 1978PubMedCrossRefGoogle Scholar
  65. 65.
    Rabin RA, Wolfe BB, Dibner, et al: Effects of ethanol administration and withdrawal on neurotransmitter receptor systems in C57 mice. J Pharmacol Exp Ther 213: 491–496, 1980PubMedGoogle Scholar
  66. 66.
    Tabakoff B, Luthin GR, Saito T, et al: Effects of ethanol on receptor-adenylate cyclase coupling. Fed Proc 42: 902, 1983Google Scholar
  67. 67.
    Bustos G, Liberona JL, Gysling K: Regulation of transmitter synthesis and release in mesolimbic dopaminergic nerve terminals. Effect of ethanol. Biochem Pharmacol 30: 2157–2164, 1981PubMedCrossRefGoogle Scholar
  68. 68.
    Morgenroth VH, Walters JR, Roth RH: Dopaminergic neurons—Alteration in the kinetic properties of tyrosine hydroxylase after cessation of impulse flow. Biochem Pharmacol 25: 655–661, 1976PubMedCrossRefGoogle Scholar
  69. 69.
    Bustos G, Roth RH: Effect of acute ethanol treatment on transmitter synthesis and metabolism in central dopaminergic neurons. J Pharm Pharmacol 28: 580–582, 1976PubMedCrossRefGoogle Scholar
  70. 70.
    Urwyler S, Tabakoff B: Stimulation of dopamine synthesis and release by morphine and [2D-Ala, 5-D-Leu]enkephalin in the mouse striatum in vivo. Life Sci 28: 2277–2286, 1981PubMedCrossRefGoogle Scholar
  71. 71.
    Kehr W, Carlsson A, Lindqvist M: A method for determination of 3,4-dihydroxyphenylalanine (DOPA) in brain. N-S Arch Pharmacol 274: 273–280, 1972CrossRefGoogle Scholar
  72. 72.
    Kiianmaa K, Tabakoff B: Neurochemical correlates of tolerance and strain differences in the neurochemical effects of ethanol. Pharmacol Biochem Behav 18 (Suppl 1): 383–388, 1983PubMedCrossRefGoogle Scholar
  73. 73.
    Carlsson A, Magnusson J, Svensson TH, et al: Effect of ethanol on the metabolism of brain catecholamines. Psychopharmacologia 30: 27–36, 1973PubMedCrossRefGoogle Scholar
  74. 74.
    Carlsson A, Engel J, Strombom U, et al: Suppression by dopamine agonists of the ethanol-induced stimulation of locomotor activity and brain dopamine synthesis. N-S Arch Pharmacol 283: 117–128, 1974CrossRefGoogle Scholar
  75. 75.
    Corrodi H, Fuxe K, Hokfelt T: The effect of ethanol on the activity of central catecholamine neurones in rat brain. J Pharm Pharmacol 18: 821–823, 1966PubMedCrossRefGoogle Scholar
  76. 76.
    Carlsson A, Lindqvist M: Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J Pharm Pharmacol 25: 437 440, 1973Google Scholar
  77. 77.
    Hunt WA, Majchrowicz E: Studies of neurotransmitter interactions after acute and chronic ethanol administration. Pharmacol Biochem Behav 18 (Suppl 1): 371–374, 1983PubMedGoogle Scholar
  78. 78.
    Karoum F, Wyatt RJ, Majchrowicz E: Brain concentrations of biogenic amine metabolites in acutely treated and ethanol-dependent rats. Br J Pharmacol 56: 403–411, 1976PubMedCrossRefGoogle Scholar
  79. 79.
    Lai H, Makous WL, Horita A, et al: Effects of ethanol on turnover and function of striatal dopamine. Psychopharmacology 61: 1–9, 1979PubMedCrossRefGoogle Scholar
  80. 80.
    Barbaccia ML, Bosio A, Spano PF, et al: Ethanol metabolism and striatal dopamine turnover. J Neural Transm 53: 169–177, 1982PubMedCrossRefGoogle Scholar
  81. 81.
    Fadda F, Argiolas A, Melis MR, et al: Differential effect of acute and chronic ethanol on dopamine metabolism in frontal cortex, caudate nucleus and substantia nigra. Life Sci 27: 979–986, 1980PubMedCrossRefGoogle Scholar
  82. 82.
    Baizer L, Masserano 1M, Weiner N: Ethanol-induced changes in tyrosine hydroxylase activity in brains of mice selectively bred for differences in sensitivity to ethanol. Pharmacol Biochem Behav 15: 945–949, 1981PubMedCrossRefGoogle Scholar
  83. 83.
    Alkana RL, Parker ES, Malcolm RD, et al: Interaction of apomorphine and amantadine with ethanol in men. Alcoholism: Clin Exp Res 6: 403–411, 1982CrossRefGoogle Scholar
  84. 84.
    Major LF, Ballenger JC, Goodwin FK, et al: Cerebrospinal fluid homovanillic acid in male alcoholics: Effects of disulfiram. Biol Psychiatry 12: 635–642, 1977PubMedGoogle Scholar
  85. 85.
    Orenberg EK, Zarcone VP, Renson JF, et al: The effects of ethanol ingestion on cyclic AMP, homovanillic acid and 5-hydroxyindoleacetic acid in human cerebrospinal fluid. Life Sci 19: 1669–1672, 1976PubMedCrossRefGoogle Scholar
  86. 86.
    Ritzmann, RF, Tabakoff B: Body temperature in mice: A quantitative measure of alcohol tolerance and physical dependence. J Pharmacol Exp Ther 199: 158–170, 1976PubMedGoogle Scholar
  87. 87.
    Lucchi L, Lupini M, Govoni S, et al: Ethanol and dopaminergic systems. Pharmacol Biochem Behav 18 (Suppl 1): 379–382, 1983PubMedCrossRefGoogle Scholar
  88. 88.
    Tabakoff B, Hoffman PL: Alterations in receptors controlling dopamine synthesis after chronic ethanol ingestion. J Neurochem 31: 1223–1229, 1978PubMedCrossRefGoogle Scholar
  89. 89.
    Ahtee L, Svarstrom-Fraser M: Effect of ethanol dependence and withdrawal on the catecholamines in rat brain and heart. Acta Pharmacol Toxicol 36: 289–298, 1975Google Scholar
  90. 90.
    Darden JH, Hunt WA: Reduction of striatal dopamine release during an ethanol withdrawal syndrome. J Neurochem 29: 1143–1145, 1977PubMedCrossRefGoogle Scholar
  91. 91.
    Mullin Mi, Ferko, AP: Alterations in dopaminergic function after subacute ethanol administration. J Pharmacol Exp Ther 225: 694–698, 1983Google Scholar
  92. 92.
    Liljequist S, Engel J: The effect of chronic ethanol administration on central neurotransmitter mechanisms. Med Biol 57: 199–210, 1979PubMedGoogle Scholar
  93. 93.
    Borg V, Weinholdt T: Bromocriptine in the treatment of the alcohol withdrawal syndrome. Acta Psychiatr Scand 65: 101–111, 1982PubMedCrossRefGoogle Scholar
  94. 94.
    Seeman P: Brain dopamine receptors. Pharmacol Rev 32: 229–313, 1980PubMedGoogle Scholar
  95. 95.
    Hruska RE, Silbergeld EK: Inhibition of 3H-spiroperidol binding by in vitro addition of ethanol. J Neurochem 35: 750–752, 1980PubMedCrossRefGoogle Scholar
  96. 96.
    Rabin RA, Molinoff PB: Activation of adenylate cyclase by ethanol in mouse striatal tissue. J Pharmacol Exp Ther 216: 129–134, 1981PubMedGoogle Scholar
  97. 97.
    Tabakoff B, Hoffman PL: Development of functional dependence on ethanol in dopaminergic systems. J Pharmacol Exp Ther 208: 216–222, 1979PubMedGoogle Scholar
  98. 98.
    Barbaccia ML, Bosio A, Lucchi L, et al: Neuronal mechanisms regulating ethanol effects on the dopaminergic system. Life Sci 30: 2163–2170, 1982PubMedCrossRefGoogle Scholar
  99. 99.
    Engel J, Liljequist S: The effect of long-term ethanol treatment on the sensitivity of the dopamine receptors in the nucleus accumbens. Psychopharmacology 49: 253–257, 1976PubMedCrossRefGoogle Scholar
  100. 100.
    Liljequist S: Changes in the sensitivity of dopamine receptors in the nucleus accumbens and in the striatum induced by chronic ethanol administration. Acta Pharmacol 43: 19–28, 1978CrossRefGoogle Scholar
  101. 101.
    Tabakoff B, Hoffman PL, Ritzmann RF: Dopamine receptor function after chronic ingestion of ethanol. Life Sci 23: 643–648, 1978PubMedCrossRefGoogle Scholar
  102. 102.
    Black RF, Hoffman PL, Tabakoff B: Receptor-mediated dopaminergic function after ethanol withdrawal. Alcoholism: Clin Exp Res 4: 294–297, 1980CrossRefGoogle Scholar
  103. 103.
    Van Thiel DH, Gavaler JS, Lester R, et al: Plasma estrone, prolactin, neurophysin and sex steroid-binding globulin in chronic alcoholic men. Metabolism 24: 1015–1019, 1975PubMedCrossRefGoogle Scholar
  104. 104.
    Majumdar SK: Serum prolactin levels during the hangover phase of the ethanol withdrawal syndrome. Neuroendocrinol Lett 4: 253–259, 1982Google Scholar
  105. 105.
    Neill JD, Frawley LS, Plostky PM, et al: Dopamine in hypophyseal stalk blood of the Rhesus monkey and its role in regulating prolactin secretion. Endocrinology 108: 489–494, 1981PubMedCrossRefGoogle Scholar
  106. 106.
    Seilicovich A, Rettori V, Koch OR, et al: The effect of acute and chronic ethanol administration on prolactin secretion in male rats. J Androl 3: 344–348, 1982Google Scholar
  107. 107.
    Pokras R, Tabakoff B: Ethanol alters the sensitivity of the dopamine receptor mediating the inhibition of prolactin release. Alcoholism: Clin Exp Res 6: 151, 1982Google Scholar
  108. 108.
    Pokras R, Tabakoff B: On the mechanism by which dopamine inhibits prolactin release in the anterior pituitary. Life Sci 31: 2587–2593, 1982PubMedCrossRefGoogle Scholar
  109. 109.
    Tabakoff B, Ritzmann RF, Boggan WO: Inhibition of the transport of 5-hydroxyindoleacetic acid from brain by ethanol. J Neurochem 24: 1043–1051, 1975PubMedCrossRefGoogle Scholar
  110. 110.
    Weingartner H, Rudorfer MV, Buchsbaum MS, et al: Effect of serotonin on memory impairments produced by ethanol. Science 221: 472–474, 1983PubMedCrossRefGoogle Scholar
  111. ll. Branchey L, Shaw S, Lieber CS: Ethanol impairs tryptophan transport into the brain and depresses serotonin. Life Sci 29: 2751–2755, 1981CrossRefGoogle Scholar
  112. 112.
    Tabakoff B, Hoffman PL, Moses F: Neurochemical correlates of ethanol withdrawal: Alterations in serotonergic function. J Pharm Pharmacol 29: 471–476, 1977PubMedCrossRefGoogle Scholar
  113. 113.
    Collier HOJ, Hammond MD, Schneider C: Effects of drugs affecting endogenous amines or cyclic nucleotides on ethanol withdrawal head twitches in mice. Br J Pharmacol 58: 9–16, 1976PubMedCrossRefGoogle Scholar
  114. 114.
    Carmichael FJ, Israel Y: Effects of ethanol on neurotransmitter release by rat brain cortical slices. J Pharmacol Exp Ther 193: 824–834, 1975PubMedGoogle Scholar
  115. 115.
    Kalant H, Israel Y, Mahon MA: The effect of ethanol on acetylcholine synthesis, release and degradation in brain. Can J Physiol Pharmacol 45: 172–176, 1967PubMedCrossRefGoogle Scholar
  116. 116.
    Erickson CK, Graham DT: Alteration of cortical and reticular acetylcholine release by ethanol in vivo. J Pharmacol Exp Ther 185: 583–593, 1973PubMedGoogle Scholar
  117. 117.
    Sinclair JG, Lo GF: Acute tolerance to ethanol on the release of acetylcholine from the cat cerebral cortex. Can J Physiol Pharmacol 56: 668–670, 1978PubMedCrossRefGoogle Scholar
  118. 118.
    Hunt WA, Dalton TK: Regional brain acetylcholine levels in rats acutely treated with ethanol or rendered ethanol dependent. Brain Res 109: 628–631, 1976PubMedCrossRefGoogle Scholar
  119. 119.
    Cohen EL, Wurtman RJ: Brain acetylcholine: Increase after systemic choline administration. Life Sci 16: 1095–1102, 1975PubMedCrossRefGoogle Scholar
  120. 120.
    Kuhar MJ, Murrin LC: Sodium-dependent high affinity choline uptake. J Neurochem 30: 15–21, 1978PubMedCrossRefGoogle Scholar
  121. 121.
    Murrin LC, de Haven RN, Kuhar MJ: On the relationship between 3H-choline uptake activation and 3H-acetylcholine release. J Neurochem 29: 681–687, 1977PubMedCrossRefGoogle Scholar
  122. 122.
    Durkin TP, Hashem-Zadeh H, Mandel P, et al: A comparative study of the acute effects of ethanol on the cholinergic system in hippocampus and striatum of inbred mouse strains. J Pharmacol Exp Ther 220: 203–208, 1982PubMedGoogle Scholar
  123. 123.
    Howerton TC, Marks MJ, Collins AC: Norepinephrine, gamma-aminobutyric acid and choline reuptake kinetics and the effects of ethanol in long-sleep and short-sleep mice. Subst Alcohol Actions Misuse 3: 89–99, 1982PubMedGoogle Scholar
  124. 124.
    Hunt WA, Majchrowicz E, Dalton T: Alterations in high-affinity choline uptake in brain after acute and chronic ethanol treatment. J Pharmacol Exp Ther 210: 259–263, 1979PubMedGoogle Scholar
  125. 125.
    Clark JW, Kalant H, Carmichael FJ: Effect of ethanol tolerance on release of acetylcholine and norepinephrine by rat cerebral cortex slices. Can J Physiol Pharmacol 55: 758–768, 1977PubMedCrossRefGoogle Scholar
  126. 126.
    Rawat AK: Brain levels and turnover rates of presumptive neurotransmitters as influenced by administration and withdrawal of ethanol in mice. J Neurochem 22: 915–922, 1974PubMedCrossRefGoogle Scholar
  127. 127.
    Ebel A, Vigran R, Mack G, et al: Cholinergic involvement in ethanol intoxication and withdrawal-induced seizure susceptibility. Psychopharmacology 61: 251–254, 1979PubMedCrossRefGoogle Scholar
  128. 128.
    Nordberg A, Larsson C, Perdahl E, et al: Changes in cholinergic activity in human hippocampus following chronic alcohol abuse. Pharmacol Biochem Behav 18 (Suppl 1): 397–400, 1983PubMedCrossRefGoogle Scholar
  129. 129.
    Tabakoff B, Munoz-Marcus M, Fields JZ: Chronic ethanol feeding produces an increase in msucarinic cholinergic receptors in mouse brain. Life Sci 25: 2173–2180, 1979PubMedCrossRefGoogle Scholar
  130. 130.
    Nordberg A, Wahlstrom G: Tolerance, physical dependence and changes in msucarinic receptor binding sites after chronic ethanol treatment in the rat. Life Sci 31: 277–287, 1982PubMedCrossRefGoogle Scholar
  131. 131.
    Yoshida K, Engel J, Liljequist S: The effect of chronic ethanol administration on high affinity 3H-nicotinic binding in rat brain. N-S Arch Pharmacol 321: 74–76, 1982CrossRefGoogle Scholar
  132. 132.
    Smith CM: The pharmacology of sedative/hypnotics, alcohol and anesthetics: Sites and mechanisms of action, in Martin W (ed): Handbook of Experimental Pharmacology, Vol 45(1). Berlin, Springer-Verlag, 1977, p 413Google Scholar
  133. 133.
    Liljequist S, Engel J: Effects of GABA ergic agonists and antagonists on various ethanol-induced behavioral changes. Psychopharmacology 78: 71–75, 1982PubMedCrossRefGoogle Scholar
  134. 134.
    Frye GD, Breese, GR: GABA ergic modulation of ethanol-induced motor impairment. J Pharmacol Exp Ther 223: 750–756, 1982PubMedGoogle Scholar
  135. 135.
    Martz A, Deitrich RA, Harris RA: Behavioral evidence for the involvement of gammaaminobutyric acid in the actions of ethanol. Eur J Pharmacol 89: 53–62, 1983PubMedCrossRefGoogle Scholar
  136. 136.
    Sutton I, Simmonds MA: Effects of acute and chronic ethanol on the gamma-aminobutyric acid system in rat brain. Biochem Pharmacol 22: 1685–1692, 1973PubMedCrossRefGoogle Scholar
  137. 137.
    Hakkinen HM, Kulonen E: Ethanol intoxication and the activities of glutamate decarboxylase and gamma-aminobutyric aminotransferase in rat brain. J Neurochem 33: 943–946, 1979PubMedCrossRefGoogle Scholar
  138. 138.
    Wixon HN, Hunt WA: Effect of acute and chronic ethanol treatment on gamma-aminobutyric acid levels and on aminooxyacetic acid-induced GABA accumulation. Subst Alcohol Actions Misuse 1:481–491, 1980Google Scholar
  139. 139.
    Volicer L, Klosowicz BA: Effect of ethanol and stress on gamma-aminobutyric acid and guanosine 3’,5’-monophosphate levels in the rat brain. Biochem Pharmacol 28: 2677–2679, 1979PubMedCrossRefGoogle Scholar
  140. 140.
    Sytinsky IA, Guzikov BM, Gomanko MV, et al: The gamma-aminobutyric acid (GABA) system in brain during acute and chronic ethanol intoxication. J Neurochem 25: 43–48, 1975PubMedCrossRefGoogle Scholar
  141. 141.
    Leitch GL, Backes DJ, Siegman FS, et al: Possible role of GABA in the development of tolerance to alcohol. Experientia 33: 496–497, 1977PubMedCrossRefGoogle Scholar
  142. 142.
    Claus D, Kim JS, Kornhuber ME, et al: Einfluss von aethanol auf die neurotransmitter glutamat and GABA. Arch Psychiatr Nervenkr 232: 183–189, 1982PubMedCrossRefGoogle Scholar
  143. 143.
    Volicer L: GABA levels and receptor binding after acute and chronic ethanol administration. Brain Res Bull 5: 809–813, 1980CrossRefGoogle Scholar
  144. 144.
    Cooper BR, Viik K, Ferris RM, et al: Antagonism of the enhanced susceptibility to audiogenic seizures during alcohol withdrawal in the rat by gamma-aminobutyric acid (GABA) and GABAmimetic agents. J Pharmacol Exp Ther 209: 396–403, 1979PubMedGoogle Scholar
  145. 145.
    Ticku MK, Burch T: Alterations in gamma-aminobutyric acid receptor sensitivity following acute and chronic ethanol treatment. J Neurochem 34: 417–423, 1980PubMedCrossRefGoogle Scholar
  146. 146.
    Ticku MK: The effects of acute and chronic ethanol administration and its withdrawal on gamma-aminobutyric acid receptor binding in rat brain. Br J Pharmacol 70: 403–410, 1980PubMedCrossRefGoogle Scholar
  147. 147.
    Linnoila M, Stowell L, Marangos PJ, et al: Effect of ethanol and ethanol withdrawal on 3Hmuscimol binding and behavior in the rat: A pilot study. Acta Pharmacol Toxicol 49: 407–411, 1981CrossRefGoogle Scholar
  148. 148.
    Rohde BH, Harris RA: GABA and flunitrazepam binding to neuroblastoma cell membranes—Effects of growth conditions, ethanol and pentobarbital. Brain Res 253: 133–141, 1982PubMedCrossRefGoogle Scholar
  149. 149.
    Unwin JW, Taberner PV: Sex and strain differences in GABA receptor binding after chronic ethanol drinking in mice. Neuropharmacology 19: 1257–1259, 1980PubMedCrossRefGoogle Scholar
  150. 150.
    Volicer L, Biagoni TM: Effect of ethanol administration and withdrawal on GABA receptor binding in rat cerebral cortex. Subst Alcohol Actions Misuse 3: 31–39, 1982PubMedGoogle Scholar
  151. 151.
    Liljequist S, Engel J: Attenuation of the gamma-butyrolactone-induced increase in DOPA accumulation by chronic ethanol administration. J Neural Transm 46: 195–204, 1979PubMedCrossRefGoogle Scholar
  152. 152.
    Bosio A, Lucchi L, Spano PF, et al: Central toxic effects of chronic ethanol treatment: Actions on GABA and benzodiazepine recognition sites. Toxicol Lett 13: 99–104, 1982PubMedCrossRefGoogle Scholar
  153. 153.
    Sellers EM, Busto U: Benzodiazepines and ethanol: Assessment of the effects and consequences of psychotropic drug interactions. J Clin Psychopharmacol 2: 249–262, 1982PubMedCrossRefGoogle Scholar
  154. 154.
    Mattila MJ, Aranko K, Seppala T: Acute effects of buspirone and alcohol on psychomotor skills. J Clin Psychiatry 43: 56–61, 1982PubMedGoogle Scholar
  155. 155.
    Paiva ES, Linnoila M, Routledge P, et al: Actions and interactions of diazepam and alcohol on psychomotor skills in young and middle-aged subjects. Acta Pharmacol Toxicol 50: 363–369, 1982Google Scholar
  156. 156.
    Sellers EM, Kalant H: Alcohol intoxication and withdrawal. N Engl J Med 294: 757–762, 1976PubMedCrossRefGoogle Scholar
  157. 157.
    Olsen RW: GABA-benzodiazepine-barbiturate receptor-ionophore complex. Mol Cell Biochem 39: 261–279, 1981PubMedCrossRefGoogle Scholar
  158. 158.
    Davis WC, Ticku M: Ethanol enhances 3H-diazepam binding at the benzodiazepine-gammaaminobutyric acid receptor-ionophore complex. Mol Pharmacol 20: 287–294, 1981PubMedGoogle Scholar
  159. 159.
    Karobeth M, Rogers J, Bloom F: Benzodiazepine receptors remain unchanged after chronic ethanol administration. Neuropharmacology 19: 125–128, 1980CrossRefGoogle Scholar
  160. Ticku M, Burch TP, Davis WC: The interactions of ethanol with the benzodiazepine-GABA receptor-ionophore complex. Pharmacol Biochem Behav 18(Suppl 1):15–18, 1983Google Scholar
  161. 161.
    Kochman RL, Hirsch JD, Clay GA: Changes in H-diazepam receptor binding after subacute ethanol administration. Res Commun Subst Abuse 2: 135–144, 1981Google Scholar
  162. 162.
    Freund G: Benzodiazepine receptor loss in brains of mice after chronic ethanol consumption. Life Sci 27: 987–992, 1980PubMedCrossRefGoogle Scholar
  163. 163.
    Michaelis EK, Mulvaney MJ, Freed W.1: Effects of acute and chronic ethanol intake on synaptosomal glutamate binding activity. Biochem Pharmacol 27: 1685–1691, 1978PubMedCrossRefGoogle Scholar
  164. 164.
    Michaelis EK, Chang HH, Roy S, et al: Ethanol effects on synaptic glutamate receptor function and on membrane lipid organization. Pharmacol Biochem Behav 18 (Suppl 1): 1–6, 1983PubMedCrossRefGoogle Scholar
  165. 165.
    Olson G, Olson RD, Kastin Ai, et al: Endogenous opiates: 1981. Peptides 3: 1039–1072, 1982PubMedCrossRefGoogle Scholar
  166. 166.
    Guerin JM, Friedberg G: Naloxone and ethanol intoxication. Ann Intern Med 97: 932, 1982PubMedCrossRefGoogle Scholar
  167. 167.
    Jefferys DB, Flanagan RF, Volans GN: Reversal of ethanol-induced coma by naloxone. Lancet 1: 308–309, 1980PubMedCrossRefGoogle Scholar
  168. 168.
    Lyon LJ, Antony J: Reversal of alcohol coma by naloxone. Ann Intern Med 96: 464–465, 1982PubMedCrossRefGoogle Scholar
  169. 169.
    Khanna JM, Mayer JM, Kalant H, et al: Effect of naloxone on ethanol-and pentobarbital-induced narcosis. Can J Physiol Pharmacol 60: 1315–1318, 1982PubMedCrossRefGoogle Scholar
  170. 170.
    Jeffcoate WJ, Herbert M, Cullen MH, et al: Prevention of the effects of alcohol intoxication by naloxone. Lancet 2: 1157–1159, 1979PubMedCrossRefGoogle Scholar
  171. 171.
    Sorenson SC, Mattison K: Naloxone as an antagonist in severe alcohol intoxication. Lancet 2: 688–689, 1978Google Scholar
  172. 172.
    Triana E, Frances RI, Stokes PE: The relationship between endorphins and alcohol-induced subcortical activity. Am J Psychiatry 137: 491–493, 1980PubMedCrossRefGoogle Scholar
  173. 173.
    Lignian H, Fontaine J, Askenasi R: Naloxone and alcohol intoxication in the dog. Hum Toxicol 2: 221–225, 1983PubMedCrossRefGoogle Scholar
  174. 174.
    Hemmingsen R, Sorensen SC: Absence of an effect of naloxone on ethanol intoxication and withdrawal reaction. Acta Pharmacol Toxico 46: 62–65, 1980CrossRefGoogle Scholar
  175. 175.
    Manila MJ, Nuomo E, Seppalla T: Naloxone is not an effective antagonist of ethanol. Lancet 1: 775–776, 1981Google Scholar
  176. 176.
    Sawynok J, Pinsky C, LaBella FS: Minireview on the specificity of naloxone as an opiate antagonist. Life Sci 25: 1621–1632, 1979PubMedCrossRefGoogle Scholar
  177. 177.
    Boada J, Feria M, Sanz E: Inhibitory effect of naloxone on ethanol-induced antinociception. Pharmacol Res Commun 13: 673–678, 1981PubMedCrossRefGoogle Scholar
  178. 178.
    Berkowitz BA, Finck AD, Ngai SH: Nitrous oxide analgesia: Reversal by naloxone and development of tolerance. J Pharmacol Exp Ther 203: 539–547, 1976Google Scholar
  179. 179.
    Badawy AA-B, Evans M: The mechanism of the antagonism by naltrexone of acute alcohol intoxication. Br J Pharmacol 74: 514–516, 1981PubMedCrossRefGoogle Scholar
  180. 180.
    Kiianmaa K, Hoffman PL, Tabakoff B: Antagonism of the behavioral effects of ethanol by naltrexone in BALB/c, C57B1/6 and DBA/2 mice. Psychopharmacology 79: 291–294, 1983PubMedCrossRefGoogle Scholar
  181. 181.
    Cicero TJ, Newman KS, Gerrity M, et al: Ethanol inhibits the naloxone-induced release of luteinizing hormone-releasing hormone from the hypothalamus of the male rat. Life Sci 31: 1587–1596, 1982PubMedCrossRefGoogle Scholar
  182. 182.
    Seizinger BR, Bovermann K, Maysinger D, et al: Differential effects of acute and chronic ethanol treatment on particular opioid peptide systems in discrete regions of brain and pituitary. Pharmacol Biochem Behav 18 (Suppl 1): 361–369, 1983PubMedCrossRefGoogle Scholar
  183. 183.
    Schulz R, Wuster M, Duka T, et al: Acute and chronic ethanol treatment changes endorphin levels in brain and pituitary. Psychopharmacology 68: 221–227, 1980PubMedCrossRefGoogle Scholar
  184. 184.
    Ryder S, Straus E, Lieber CS, et al: Cholecystokinin and enkephalin levels following ethanol administration in rats. Peptides 2: 223–226, 1981PubMedCrossRefGoogle Scholar
  185. 185.
    Gianoulakis C, Woo N, Drovin JN, et al: Biosynthesis of beta-endorphin by the neurointermediate lobe from rats treated with morphine or alcohol. Life Sci 29: 1973–1982, 1981PubMedCrossRefGoogle Scholar
  186. 186.
    Genazzani AR, Nappi G, Facchinetti F, et al: Central deficiency of beta-endorphin in alcohol addicts. J Clin Endocrinol Metab 55: 583–586, 1982PubMedCrossRefGoogle Scholar
  187. 187.
    Borg S, Kvande H, Rydberg U, et al: Endorphin levels in human cerebrospinal fluid during alcohol intoxication and withdrawal. Psychopharmacology 78: 101–103, 1982PubMedCrossRefGoogle Scholar
  188. 188.
    Pfeiffer A, Herz A: Discrimination of three opiate receptor binding sites with the use of a computerized curve-fitting technique. Mol Pharmacol 21: 266–271, 1981Google Scholar
  189. 189.
    Hiller JM, Angel LM, Simon EJ: Multiple opiate receptors: Alcohol selectively inhibits binding to delta receptors. Science 214: 468–469, 1981PubMedCrossRefGoogle Scholar
  190. 190.
    Gianoulakis C: Long-term ethanol alters the binding of ‘H-opiates to brain membranes. Life Sci 33: 725–733, 1983PubMedCrossRefGoogle Scholar
  191. 191.
    Tabakoff B, Hoffman PL: Alcohol interactions with brain opiate receptors. Life Sci 32: 192–204, 1983CrossRefGoogle Scholar
  192. 192.
    Jorgensen H, Hole K: Does ethanol stimulate brain opiate receptors? Studies on receptor binding and naloxone inhibition of ethanol-induced effects. Eur J Pharmacol 75: 223–229, 1981PubMedCrossRefGoogle Scholar
  193. 193.
    Hoffman PL, Chung CT, Tabakoff B: Effects of ethanol, temperature, and endogenous regulatory factors on the characteristics of striatal opiate receptors. J Neurochem 43: 1003–1010, 1984PubMedCrossRefGoogle Scholar
  194. 194.
    Hoffman PL, Tabakoff B: Ethanol modulates the physiological regulation of opiate receptor function. Alcoholism: Clin Exp Res 7 (1): 112, 1983Google Scholar
  195. 195.
    Levine AS, Hess S, Morley JE: Alcohol and the opiate receptor. Alcoholism: Clin Exp Res 7: 83–84, 1983CrossRefGoogle Scholar
  196. 196.
    Pert CB, Snyder SH: Opiate receptor binding of agonists and antagonists affected differentially by sodium. Mol Pharmacol 10: 868–879, 1974Google Scholar
  197. 197.
    Pfeiffer A, Sadee W, Herz A: Differential regulation of the mu, delta and kappa opiate receptor subtypes by guanyl nucleotide and metal ion. Neuroscience 7: 912–917, 1982Google Scholar
  198. 198.
    Hoffman PL, Urwyler S, Tabakoff B: Alterations in opiate receptor function after chronic ethanol exposure. J Pharmacol Exp Ther 222: 182–189, 1982PubMedGoogle Scholar
  199. 199.
    Tabakoff B, Urwyler S, Hoffman PL: Ethanol alters kinetic characteristics and function of striatal morphine receptors. J Neurochem 37: 518–521, 1981PubMedCrossRefGoogle Scholar
  200. 200.
    Pfeiffer A, Seizinger BR, Herz A: Chronic ethanol imbibition interferes with S, but not with opiate receptors. Neuropharmacology 20: 1229–1232, 1981PubMedCrossRefGoogle Scholar
  201. 201.
    Wood PL, Stotland M, Richard JW, et al: Actions of mu, sigma, delta and agonist/antagonist opiates on striatal dopaminergic function. J Pharmacol Exp Ther 215: 697–703, 1980PubMedGoogle Scholar
  202. 202.
    Stein L, Belluzzi JD: Brain endorphins: Possible role in reward and memory formation. Fed Proc 38: 2468–2472, 1979PubMedGoogle Scholar
  203. 203.
    Routtenberg A: Participation of brain stimulation reward substrates in memory: Anatomical and biochemical evidence. Fed Proc 38: 2446–2453, 1979PubMedGoogle Scholar
  204. 204.
    Littenger D, Frye GD, Nemeroff CB, et al: The effects of neurotensin, beta-endorphin and bombesin on ethanol-induced behaviors jn mice. Psychopharmacology 79: 357–363, 1983CrossRefGoogle Scholar
  205. 205.
    Hoffman PL: Structural requirements for neurohypophyseal peptide maintenance of ethanol tolerance. Pharmacol Biochem Behav 17: 685–690, 1982PubMedCrossRefGoogle Scholar
  206. 206.
    Hoffman PL, Ritzmann RF, Walter R, et al: Arginine vasopressin maintains ethanol tolerance. Nature 276: 614–616, 1978PubMedCrossRefGoogle Scholar
  207. 207.
    Hoffman PL, Ritzmann RF, Tabakoff B: Neurohypophyseal peptide influences on ethanol tolerance and acute effects of ethanol. Pharmacol Biochem Behav 13 (Suppl 1): 279–284, 1980PubMedCrossRefGoogle Scholar
  208. 208.
    Rigter H, Rijk H, Crabbe JC: Tolerance to ethanol and severity of withdrawal in mice are enhanced by a vasopressin fragment. Eur J Pharmacol 64: 53–68, 1980PubMedCrossRefGoogle Scholar
  209. 209.
    Le AD, Kalant H, Khanna JM: Interaction between des-glycinamide-[Arg]vasopressin and serotonin on ethanol tolerance. Eur J Pharmacol 80: 337–345, 1982PubMedCrossRefGoogle Scholar
  210. 210.
    Bartholini G, Stadler H: Cholinergic and GABA ergic influence on the dopamine release in extrapyramidal centers, in Almgren O, Carlsson A, Engel J (eds): Chemical Tools in Catecholamine Research, Vol 2. Amsterdam, North-Holland, 1976, pp 235–241Google Scholar
  211. 211.
    Moore EK, Wuerthele SM: Regulation of nigro-striatal and tuberoinfundibular-hypophyseal dopaminergic neurons. Prog Neurobiol 13: 325–359, 1979PubMedCrossRefGoogle Scholar
  212. 212.
    Stadler H, Lloyd KG, Gadea-Ciria M, et al: Enhanced striatal acetylcholine release by chlorpromazine and its reversal by apomorphine. Brain Res 55: 476–480, 1973.PubMedCrossRefGoogle Scholar
  213. 213.
    Kebabian 1W: Biochemical regulation and physiological significance of cyclic nucleotides in the nervous system. Adv Cyclic Nucleotide Res 8: 421–508, 1977Google Scholar
  214. 214.
    Pittman QJ, Rogers J, Bloom FE: Arginine vasopressin deficient Brattleboro rats fail to develop tolerance to the hypothermic effects of ethanol. Regul Pept 4: 33–41, 1982PubMedCrossRefGoogle Scholar
  215. 215.
    Shen A, Jacobyansky A, Smith T, et al: Cyclic adenosine 3’,5’-monophosphate, adenylate cyclase and physical dependence on ethanol: Studies with tranylcypromine. Drug Alcohol Depend 2: 431–440, 1977PubMedCrossRefGoogle Scholar
  216. 216.
    Volicer L, Hurter BP: Effects of acute and chronic ethanol administration and withdrawal on adenosine 3’,5’-monophosphate and guanosine 3’,5’-monophosphate levels in the rat brain. J Pharmacol Exp Ther 200: 298–305, 1977PubMedGoogle Scholar
  217. 217.
    Orenberg EK, Renson J, Barchas JD: The effects of alcohol on cyclic AMP in mouse brain. Neurochem Res 1:659–667, 1976Google Scholar
  218. 218.
    Redos JD, Hunt WA, Catravas GN: Lack of alteration in regional brain adenosine-3’,5’-cyclic monophosphate levels after acute and chronic treatment with ethanol. Life Sci 18: 989–992, 1976PubMedCrossRefGoogle Scholar
  219. 219.
    Ferko AP, Bobyock E, Chernick WS: Regional rat brain content of adenosine 3’,5’-cyclic monophosphate and guanosine 3’,5’-cyclic monophosphate after acute and subacute treatment with ethanol. Toxicol Appl Pharmacol 4: 447–455, 1982CrossRefGoogle Scholar
  220. 220.
    Kuriyama K, Israel MA: Effect of ethanol administration on cyclic 3’,5’-adenosine mono-phosphate metabolism in brain. Biochem Pharmacol 22: 2919–2922, 1973PubMedCrossRefGoogle Scholar
  221. 221.
    Zimmer R, Cramer H, Athen D, et al: Changes in cerebrospinal fluid cyclic nucleotides in alcohol-dependent patients suffering from delerium tremens. Biol Psychiatry 17: 837–843, 1982PubMedGoogle Scholar
  222. 222.
    Dodson RA, Johnson WE: Effects of ethanol, arecoline, atropine and nicotine, alone and in various combinations, on rat cerebellar cyclic guanosine 3’,5’-monophosphate. Neuropharmacology 18: 871–876, 1979PubMedCrossRefGoogle Scholar
  223. 223.
    Hunt WA, Redos JD, Dalton TK, et al: Alterations in brain cyclic guanosine 3’,5’-monophosphate levels after acute and chronic treatment with ethanol. J Pharmacol Exp Ther 201: 103–109, 1977PubMedGoogle Scholar
  224. 224.
    Church AC, Feller D: The influence of mouse genotype on the changes in brain cyclic nucleotide levels induced by acute alcohol administration. Pharmacol Biochem Behav 10: 335–338, 1979PubMedCrossRefGoogle Scholar
  225. 225.
    Kuriyama K: Ethanol-induced changes in activities of adenylate cyclase, guanylate cyclase and cyclic adenosine 3’,5’-monophosphate dependent protein kinase in the brain and liver. Drug Alcohol Depend 2: 335–348, 1977PubMedCrossRefGoogle Scholar
  226. 226.
    Israel MA, Kimura H, Kuriyama K: Changes in activity and hormonal sensitivity of brain adenyl cyclase following chronic ethanol administration. Experientia 28: 1322–1323, 1972PubMedCrossRefGoogle Scholar
  227. 227.
    Volicer L, Mirin R, Gold BI: Effect of ethanol on the cyclic AMP system in rat brain. J Stud Alcohol 38: 11–24, 1977PubMedGoogle Scholar
  228. 228.
    Hoffman PL, Tabakoff B: Effects of ethanol on Arrhenius parameters and activity of mouse striatal adenylate cyclase. Biochem Pharmacol 31.3101–3106, 1982Google Scholar
  229. 229.
    von Hungen K, Baxter CF: Sensitivity of rat brain adenylate cyclase to activation by calcium and ethanol after chronic exposure to ethanol. Biochem Biophys Res Commun 106: 1078–1082, 1982PubMedCrossRefGoogle Scholar
  230. 230.
    Spiegel AM, Downs RW Jr: Guanine nucleotides: Key regulators of hormone receptor-adenylate cyclase interaction. Endocr Rev 2: 275–305, 1981PubMedCrossRefGoogle Scholar
  231. 231.
    Stadel JM, deLean A, Lefkowitz RI: Molecular mechanisms of coupling in hormone receptoradenylate cyclase systems. Adv Enzymol 53: 1–43, 1982PubMedGoogle Scholar
  232. 232.
    Cooper DMF: Biomodal regulation of adenylate cyclase. FEBS Lett 138: 157–163, 1982PubMedCrossRefGoogle Scholar
  233. 233.
    Hoffman PL, Luthin GR, Theodoropoulos D, et al: Ethanol effects on striatal dopamine receptor-coupled adenylate cyclase and on striatal opiate receptors. Pharmacol Biochem Behav 18 (Suppl 1): 355–359, 1983PubMedCrossRefGoogle Scholar
  234. 234.
    Luthin GR, Tabakoff B: Activation of adenylate cyclase by alcohols requires the nucleotide-binding protein. J Pharmacol Exp Ther 228: 579–587, 1984PubMedGoogle Scholar
  235. 235.
    Rabin RA, Molinoff PB: Multiple sites of action of ethanol on adenylate cyclase. J Pharmacol Exp Ther 227: 551–556, 1983PubMedGoogle Scholar
  236. 236.
    Kamikubo K, Nozaki M, Fujimura H: Inhibition of adenylate cyclase by GTP and its modulation by opiate receptor in rat caudate nucleus. Jpn J Pharmacol 31: 175–184, 1981PubMedCrossRefGoogle Scholar
  237. 237.
    Law PY, Wu J, Koehler JE, et al: Demonstration and characterization of opiate inhibition of the striatal adenylate cyclase. J Neurochem 36: 1834–1846, 1981PubMedCrossRefGoogle Scholar
  238. 238.
    Cooper DMF, Londos C, Gill DL, et al: Opiate receptor-mediated inhibition of adenylate cyclase in rat striatal plasma membranes. J Neurochem 38: 1164–1167, 1982PubMedCrossRefGoogle Scholar
  239. 239.
    Blume AJ, Lichtshtein D, Boone G: Coupling of opiate receptors to adenylate cyclase: Requirement for Na* and GTP. Proc Nat! Acad Sci USA 76: 5626–5630, 1979PubMedCrossRefGoogle Scholar
  240. 240.
    Michel T, Lefkowitz RI: Hormonal inhibition of adenylate cyclase. J Bio! Chem 257: 13557–13563, 1982Google Scholar
  241. 241.
    Koski G, Streaty RA, Klee WA: Modulation of sodium-sensitive GTPase by partial opiate agonists. J Bio! Chem 257: 14035–14040, 1982Google Scholar
  242. 242.
    Childers SR, Snyder SH: Differential regulation by guanine nucleotides of opiate agonist and antagonist receptor interactions. J Neurochem 34: 583–593, 1980PubMedCrossRefGoogle Scholar
  243. 243.
    Rubin E, Rottenberg H: Ethanol and biological membranes: Injury and adaptation. Pharmacol Biochem Behav 18 (Suppl l): 7–13, 1983PubMedCrossRefGoogle Scholar
  244. 244.
    Goldstein DB, Chin JA, Lyon RC: Ethanol disordering of spin-labeled mouse brain membranes: Correlation with genetically determined ethanol sensitivity of mice. Proc Natl Acad Sci USA 79: 4231–4233, 1982PubMedCrossRefGoogle Scholar
  245. 245.
    Harris RA, Schroeder F: Ethanol and the physical properties of brain membranes: Fluorescence studies. Mol Pharmacol 20: 128–137, 1981PubMedGoogle Scholar
  246. 246.
    Chin JH, Goldstein DB: Drug tolerance in biomembranes: A spin-label study of the effects of ethanol. Science 196: 684–685, 1976CrossRefGoogle Scholar
  247. 247.
    Goldstein DB, Chin JH, Lyon RC: Ethanol disordering of spin-labelled mouse brain membranes: Correlation with genetically-determined ethanol sensitivity of mice. Proc Natl Acad Sci USA 79: 4231–4233, 1982PubMedCrossRefGoogle Scholar
  248. 248.
    Farias RN, Bloj B, Morero RD, et al: Regulation of allosteric membrane-bound enzymes through changes in membrane lipid composition. Biochim Biophys Acta 415: 231–251, 1975PubMedCrossRefGoogle Scholar
  249. 249.
    Harris RA, Schroeder F: Effects of barbiturates and ethanol on the physical properties of brain membranes. J Pharmacol Exp Ther 223: 424–431, 1982PubMedGoogle Scholar
  250. 250.
    Chin JH, Goldstein DB: Membrane disordering action of ethanol. Variation with membrane cholesterol content and depth of the spin-label probe. Mol Pharmacol 19: 425–431, 1981PubMedGoogle Scholar
  251. 251.
    Johnson DA, Lee NM, Cooke R, et al: Ethanol-induced fluidization of brain lipid biolayers: Required presence of cholesterol in membranes for the expression of tolerance. Mol Pharmacol 15: 739–746, 1979PubMedGoogle Scholar
  252. 252.
    Chin JH, Parsons LM, Goldstein DB: Increased cholesterol content of erythrocyte and brain membranes in ethanol-tolerant mice. Biochim Biophys Acta 513: 358–363, 1978PubMedCrossRefGoogle Scholar
  253. 253.
    Smith TL, Gerhart MJ: Alterations in brain lipid composition of mice made physically dependent on ethanol. Life Sci 31: 1419–1425, 1982PubMedCrossRefGoogle Scholar
  254. 254.
    Parsons LM, Gallaher EJ, Goldstein DB: Rapidly developing functional tolerance to ethanol is accompanied by increased erythrocyte cholesterol in mice. J Pharmacol Exp Ther 223: 472–476, 1982PubMedGoogle Scholar
  255. 255.
    Lyon RC, Goldstein DB: Changes in synaptic membrane order associated with chronic ethanol treatment in mice. Mol Pharmacol 23: 86–91, 1983PubMedGoogle Scholar
  256. 256.
    Vrbaski SR, Grujic-Injac B, Ristic M: Effect of dietary protein level on brain phospholipids during chronic ethanol consumption. Res Commun Subst Abuse 1: 349–352, 1980Google Scholar
  257. 257.
    Ailing C, Liljequist S, Engel J: The effect of chronic ethanol administration on lipids and fatty acids in subcellular fractions of rat brain. Med Biol 60: 149–154, 1982Google Scholar
  258. 258.
    Ingram LO, Ley KD, Hoffman EM: Drug-induced changes in lipid composition of E. coli and of mammalian cells in culture: Ethanol, pentobarbital and chlorpromazine. Life Sci 22: 489–494, 1978PubMedCrossRefGoogle Scholar
  259. 259.
    Sun GY, Sun AY: Effect of chronic ethanol on phospholipid acyl groups of synaptic plasma membrane fraction isolated from guinea pig brain. Res Commun Chem Pathol Pharmacol 24: 405–408, 1979PubMedGoogle Scholar
  260. 260.
    Littleton JM, John G: Synaptosomal membrane lipids of mice during continuous exposure to ethanol. J Pharm Pharmacol 29: 579–580, 1977PubMedCrossRefGoogle Scholar
  261. 261.
    Littleton JM, John GR, Grieve SJ: Alterations in phospholipid composition in ethanol tolerance and dependence. Alcoholism: Clin Exp Res 3: 50–56, 1979CrossRefGoogle Scholar
  262. 262.
    Beaugé F, Stibler H, Kalant H: Brain synaptosomal (Na and K+)ATPase activity as an index of tolerance to ethanol. Pharmacol Biochem Behav 18 (Suppl 1): 519–524, 1983PubMedCrossRefGoogle Scholar
  263. 263.
    Guerri C, Grisolia S: Chronic ethanol treatment affects synaptosomal membrane-bound enzymes. Pharmacol Biochem Behav 18 (Suppl 1): 45–50, 1983PubMedCrossRefGoogle Scholar
  264. 264.
    Lenaz G, Curatola G, Masotti L: Perturbation of membrane fluidity. J Bioenerg Biomembr 7: 223–299, 1975CrossRefGoogle Scholar
  265. 265.
    Sedman GL, Austin L, Langford CJ: Protein turnover in brain during the development of alcohol dependence. Neurosci Lett 28: 93–99, 1982PubMedCrossRefGoogle Scholar
  266. 266.
    Goertz B: Effect of ethanol on rat brain protein synthesis. Exp Brain Res 48: 438–442, 1982Google Scholar
  267. 267.
    Noble EP, Tewari S: Protein and rinonucleic acid metabolism in brains of mice following chronic alcohol consumption. Ann NY Acad Sci 215: 333–345, 1973PubMedCrossRefGoogle Scholar
  268. 268.
    Tewari S, Fleming EW, Noble EP: Alterations in brain RNA metabolism following chronic ethanol ingestion. J Neurochem 24: 561–569, 1975PubMedCrossRefGoogle Scholar
  269. 269.
    Jarlstedt J: Experimental alcoholism in rats: Protein synthesis in subcellular fractions from cerebellum, cerebral cortex and liver after long-term treatment. J Neurochem 19: 603–608, 1972PubMedCrossRefGoogle Scholar
  270. 270.
    Renis M, Giovine A, Bertolina A: Protein synthesis in the mitochondrial and microsomal fraction from rat brain after acute or chronic ethanol administration. Life Sci 16: 1447–1457, 1975PubMedCrossRefGoogle Scholar
  271. 271.
    Frankel D, Khanna JM, LeBlanc AE, et al: Effect of p-chlorophenylalanine on the acquisition of tolerance to ethanol and pentobarbital. Psychopharmacologia 44: 247–252, 1975PubMedCrossRefGoogle Scholar
  272. 272.
    Frankel D, Khanna JM, Kalant H, et al: Effect of p-chlorophenylalanine on the acquisition of tolerance to the hypothermic effects of ethanol. Psychopharmacology 57: 239–242, 1978PubMedCrossRefGoogle Scholar
  273. 273.
    Le AD, Khanna JM, Kalant H, et al: Effect of 5,7-dihydroxytryptamine on the development of tolerance to ethanol. Psychopharmacology 67: 143–146, 1980PubMedCrossRefGoogle Scholar
  274. 274.
    Khanna JM, Kalant H, Le AD, et al: Role of serotonergic and adrenergic systems in alcohol tolerance. Prog Neuropsychopharmacol Biol Psychiatry 5: 459–465, 1981Google Scholar
  275. 275.
    Wood JM: Effect of depletion of brain 5-hydroxytryptamine by 5,7-dihydroxytryptamine on ethanol tolerance and dependence in the rat. Psychopharmacology 67: 67–72, 1980PubMedCrossRefGoogle Scholar
  276. 276.
    Ritzmann RF, Tabakoff B: Dissociation of alcohol tolerance and dependence. Nature 263: 418–420, 1976PubMedCrossRefGoogle Scholar
  277. 277.
    Wood JM, Laverty R: Effect of depletion of brain catecholamine on ethanol tolerance and dependence. Eur J Pharmacol 58: 285–293, 1979PubMedCrossRefGoogle Scholar
  278. 278.
    Le AD, Poulos CS, Cappell H: Conditioned tolerance to the hypothermic effect of ethyl alcohol. Science 206: 1109–1110, 1979PubMedCrossRefGoogle Scholar
  279. 279.
    Crowell CR, Hinson RE, Siegel S: The role of conditioned drug responses in tolerance to the hypothermic effects of ethanol. Psychopharmacology 73: 51–54, 1981PubMedCrossRefGoogle Scholar
  280. 280.
    Hinson RE, Siegel S: The contribution of Pavlovian conditioning to ethanol tolerance and dependence, in Rigter H, Crabbe JC (eds): Alcohol Tolerance and Dependence. Amsterdam, Elsevier/North-Holland Biomedical Press, 1980 p 181Google Scholar
  281. 281.
    Mansfield JB, Cunningham CL: Conditioning and extinction of tolerance to the hypothermic effect of ethanol in rats. J Comp Physiol Psychol 94: 962–969, 1980PubMedCrossRefGoogle Scholar
  282. 282.
    Melchior CL, Tabakoff B: Modification of environmentally-cued tolerance to ethanol in mice. J Pharmacol Exp Ther 219: 175–180, 1981PubMedGoogle Scholar
  283. 283.
    Hoffman PL, Melchior CL, Tabakoff B: Vasopressin maintenance of ethanol tolerance requires intact brain noradrenergic systems. Life Sci 32: 1065–1071, 1983PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Paula L. Hoffman
    • 1
  • Boris Tabakoff
    • 1
  1. 1.Division of Intramural Clinical and Biological ResearchNational Institute on Alcohol Abuse and AlcoholismBethesdaUSA

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