Effects of Alcohol on GABA-Mediated Neurotransmission

  • M. K. Ticku
  • A. K. Mehta
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 114)


Ethanol is the oldest and most widely consumed and abused drug by our society. The exact mechanism of its action, including its ability to produce tolerance and withdrawal following chronic administration, is not yet known. Ethanol has been shown to affect a variety of neurotransmitters in the CNS. Recent evidence supports the notion that ethanol may produce many of its effects by modulating ligand-gated ion channels (mediated by receptors for GAB A, NMDA, 5-HT3) in the brain. The pharmacological profile of ethanol is very similar to that of benzodiazepines and barbiturates. These classes of drugs are anxiolytics, muscle relaxants, and anticonvulsants, and their chronic use results in tolerance (BELLEVILLE and FRAZER 1957). There also exists a cross-tolerance between ethanol and barbiturates, and ethanol and benzodiazepines. Furthermore, benzodiazepines and barbiturates are effective in the management of ethanol withdrawal syndromes (GOLDSTEIN 1973). These observations suggest that a common modulatory system may be involved at least in some of the pharmacological effects of these drugs. Since the GABAergic system is involved in the pharmacological actions of benzodiazepines and barbiturates (TICKU and RASTOGI 1980; OLSEN 1982; MAKSAY and TICKU 1985; BIGGIO et al. 1992), many investigations have focused on the effects of ethanol on GABAergic pathways.


GABAA Receptor Chronic Ethanol Inverse Agonist Spinal Cord Neuron Audiogenic Seizure 
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  1. Aaronson LM, Hinman DJ, Okamoto M (1982) Effects of diazepam on ethanol withdrawal. J Pharmacol Exp Ther 221:319–325PubMedGoogle Scholar
  2. Aguayo LG (1990) Ethanol potentiates the GABAA-activated Cl~ current in mouse hippocampal and cortical neurons. Eur J Pharmacol 187:127–130PubMedCrossRefGoogle Scholar
  3. Allan AM, Harris RA (1986) Gamma-aminobutyric acid and alcohol actions: neurochemical studies of long sleep and short sleep mice. Life Sci 39:2005–2015PubMedCrossRefGoogle Scholar
  4. Allan AM, Harris RA (1987a) Acute and chronic ethanol treatments alter GAB A receptor-operated chloride channels. Pharmacol Biochem Behav 27:665–670PubMedCrossRefGoogle Scholar
  5. Allan AM, Harris RA (1987b) Involvement of neuronal chloride channels in ethanol intoxication, tolerance and dependence. Recent Dev Alcohol 5:313–325PubMedGoogle Scholar
  6. Allan AM, Spuhler KP, Harris RA (1988) y-Aminobutyric acid-activated chloride channels: relationship to genetic differences in ethanol sensitivity. J Pharmacol Exp Ther 244:866–870PubMedGoogle Scholar
  7. Belleville RE, Frazer HF (1957) Tolerance to some effects of barbiturates. J Pharmacol Exp Ther 120:469–474PubMedGoogle Scholar
  8. Biggio G, Concas A, Costa E (1992) GABAergic synaptic transmission: molecular, pharmacological and clinical aspects. Adv Biochem Psychopharmacol 47: Raven, New YorkGoogle Scholar
  9. Bonetti EP, Burkard WP, Gabi M, Möhler H (1985) The partial inverse benzodiazepine agonist Rol5–4513 antagonises acute ethanol effects in mice and rats. Br J Pharmacol 86:463PGoogle Scholar
  10. Bonetti EP, Burkard WP, Gabi M, Hinkler W, Lorez HP, Martin JR, Moehler H, Osterrieder W, Schaffner R (1989) Rol5–4513: partial inverse agonism at the benzodiazepine receptor and interaction with ethanol. Pharmacol Biochem Behav 31:733–749CrossRefGoogle Scholar
  11. Breese GR, Keir WJ, Simson PE, Criswell HE, Duncan GE, Morrow AL (1992) Localization of the β2-subunit of the GABAa receptor complex to sites where ethanol enhances GAB A. Alcohol Clin Exp Res 16:1356Google Scholar
  12. Browning MD, Bureau M, Dudek EM, Olsen RW (1990) Protein kinase C and cAMP-dependent protein kinase phosphorylates the ß subunit of the purified y-aminobutyric acid A receptor. Proc Natl Acad Sci USA 87:1315—1318PubMedCrossRefGoogle Scholar
  13. Burch TP, Thyagarajan R, Ticku MK (1983) Group selective modification of the benzodiazepine y-aminobutyric acid receptor ionophore complex reveals that low-affinity y-aminobutyric acid receptor stimulate benzodiazepine binding. Mol Pharmacol 23:52–59PubMedGoogle Scholar
  14. Carlen PL, Gurevich N, Durand D (1982) Ethanol in low doses augments calcium-mediated mechanisms measured intracellularly in hippocampal neurones. Science 215:306–309PubMedCrossRefGoogle Scholar
  15. Celentano JJ, Gibbs TT, Färb DH (1988) Ethanol potentiates GABA- and glycine- induced chloride currents in chick spinal cord neurones. Brain Res 455:377–380PubMedCrossRefGoogle Scholar
  16. Coffman JA, Petty F (1985) Plasma GABA levels in chronic alcoholics. Am J Psychiatry 142:1204–1205PubMedGoogle Scholar
  17. Cooper BR, Virk K, Ferris RM, White HL (1979) Antagonism of the enhanced susceptibility to audiogenic seizures during alcohol withdrawal in the rat by gamma-aminobutyric acid (GABA) and “GABA-mimetic” agents. J Pharmacol Exp Ther 209:396–403PubMedGoogle Scholar
  18. Cott J, Carlsson A, Engel J, Lindquist M (1976) Suppression of ethanol-induced locomotor stimulation by GABA-like drugs. Naunyn Schmiedeberg’s Arch Pharmacol 295:203–209CrossRefGoogle Scholar
  19. Dar MS, Wooles WR (1985) GABA mediation of the central effects of acute and chronic ethanol in mice. Pharmacol Biochem Behav 22:77–84PubMedCrossRefGoogle Scholar
  20. Davidoff RA (1973) Alcohol and presynaptic inhibition in an isolated spinal cord preparation. Arch Neurol 28:60–63PubMedGoogle Scholar
  21. Davis WC, Ticku MK (1981) Ethanol enhances [3H]diazepam binding at the benzodiazepine-y-aminobutyric acid receptor ionophore complex. Mol Pharmacol 20:287–294PubMedGoogle Scholar
  22. Durand D, Carlen PL (1984) Decreased neuronal inhibition in vitro after long-term administration of ethanol. Science 224:1359–1361PubMedCrossRefGoogle Scholar
  23. Fadda F, Mosca E, Colombo G, Gessa GL (1987) Protection against ethanol mortality in rats by imidazobenzodiazepine Ro 15–4513. Eur J Pharmacol 136:265–266PubMedCrossRefGoogle Scholar
  24. Freund G (1980) Benzodiazepine receptor loss in brains of mice after chronic alcohol consumption. Life Sci 27:987–992PubMedCrossRefGoogle Scholar
  25. Frye GD, McCown TJ, Breese GR (1983a) Differential sensitivity of ethanol withdrawal signs in the rat to y-aminobutyric acid (GABA) mimetics: blockade of audiogenic seizures but not forelimb tremors. J Pharmacol Exp Ther 226: 720–725PubMedGoogle Scholar
  26. Frye GD, McCown TJ, Breese GR (1983b) Characterization of susceptibility to audiogenic seizures in ethanol-dependent rats after microinjection of y- aminobutyric acid (GABA) agonists into the inferior colliculus, substantia nigra or medial septum. J Pharmacol Exp Ther 227:663–670PubMedGoogle Scholar
  27. Gage PW, Robertson B (1985) Prolongation of inhibitory postsynaptic currents by pentobarbitone, halothane and ketamine in CA1 pyramidal cells in rat hippocampus. Br J Pharmacol 85:675–681PubMedGoogle Scholar
  28. Gambarana C, Beattlie CE, Rodriguez ZR, Siegel RE (1991) Region-specific expression of messenger RNAs encoding GABAa receptor subunits in the developing rat brain. Neuroscience 45:423–432PubMedCrossRefGoogle Scholar
  29. Givens BS, Breese GR (1990) Site-specific enhancement of gamma-aminobutyric acid-mediated inhibition of neural activity by ethanol in the rat medial septal areas. J Pharmacol Exp Ther 254:528–538PubMedGoogle Scholar
  30. Goldman GD, Volicer L, Gold BI, Roth RH (1981) Cerebrospinal fluid GABA and cyclic nucleotides in alcoholics with and without seizures. Alcohol Clin Exp Res 5:431–434PubMedCrossRefGoogle Scholar
  31. Goldstein DB (1973) Alcohol withdrawal reactions in mice: effects of drugs that modify neurotransmission. J Pharmacol Exp Ther 186:1–9PubMedGoogle Scholar
  32. Goldstein DB (1979) Sodium bromide and sodium valproate: effective suppressants of ethanol withdrawal reactions in mice. J Pharmacol Exp Ther 208:223–227PubMedGoogle Scholar
  33. Gonzales LP, Hettinger MK (1984) Intranigral muscimol suppresses ethanol withdrawal seizures. Brain Res 298:163–166CrossRefGoogle Scholar
  34. Greenberg DA, Cooper EC, Gordon A, Diamond I (1984) Ethanol and the y-aminobutyric acid-benzodiazepine receptor complex. J Neurochem 42: 1062–1068PubMedCrossRefGoogle Scholar
  35. Greenblatt DJ, Greenblatt M (1972) Which drug for alcohol withdrawal? J Clin Pharmacol 12:429–431Google Scholar
  36. Guerrero-Figueroa R, Merrill M, Rye D (1970) Electrographic and behavioral effects of diazepam during alcohol withdrawal stage in cat. J Pharmacol 9: 143–150Google Scholar
  37. Hakkinen HM, Kulonen E (1976) Ethanol intoxication and gamma-aminobutyric acid. J Neurochem 27:631–633PubMedCrossRefGoogle Scholar
  38. Harris DP, Sinclair JG (1984) Ethanol-GABA interactions at the rat Purkinje cell. Gen Pharmacol 15:449–454PubMedCrossRefGoogle Scholar
  39. Harris RA, Allan AM, Daniell LC, Nixon C (1988) Antagonism of ethanol and pentobarbital actions by benzodiazepine inverse agonists: neurochemical studies. J Pharmacol Exp Ther 247:1012–1017PubMedGoogle Scholar
  40. Harrison NL, Majewska MD, Harrington JW, Barker JL (1987) Structure-activity relationships for steroid interaction with the gamma-aminobutyric acid A receptor complex. J Pharmacol Exp Ther 241:346–353PubMedGoogle Scholar
  41. Hatch RC, Jernigan AD (1988) Effect of intravenously administered putative and potential antagonists of ethanol on sleep time in ethanol narcotized mice. Life Sci 42:11–19PubMedCrossRefGoogle Scholar
  42. Hemmingsen R, Braestrup C, Nielsen M, Barry DI (1982) The benzodiazepine-GABA receptor complex during severe ethanol intoxication and withdrawal in the rat. Acta Psychiatr Scand 65:120–126PubMedCrossRefGoogle Scholar
  43. Hoffman PL, Tabakoff B, Szabo G, Suzdak PD, Paul SM (1987) Effect of an imidazobenzodiazepine, Rol5–4513, on the incoordination and hypothermia produced by ethanol and pentobarbital. Life Sci 41:611–619PubMedCrossRefGoogle Scholar
  44. Houamed KM, Bilbe G, Smart TG, Constanti A, Brown DA, Barnard EA, Richards BM (1984) Expression of functional GAB A, glycine and glutamate receptors in Xenopus oocytes injected with rat brain mRNA. Nature 310:318–321PubMedCrossRefGoogle Scholar
  45. Hunt WA (1983) The effect of ethanol on GABAergic transmission. Neurosci Biobehav Rev 7:87–95PubMedCrossRefGoogle Scholar
  46. Karobath M, Rogers J, Bloom FE (1980) Benzodiazepine receptors remain unchanged after chronic ethanol treatment. Neuropharmacology 19:125–128PubMedCrossRefGoogle Scholar
  47. Kochman RL, Hirsch JD, Clay GA (1981) Changes in [3H]-diazepam receptor binding after subacute ethanol administration. Res Commun Subst Abuse 2: 135–144Google Scholar
  48. Kofuji P, Wang JB, Moss SJ, Huganir RL, Burt DR (1991) Generation of two forms of the y-aminobutyric acid receptorA y2subunit in mice by alternative splicing. J Neurochem 56:713–715PubMedCrossRefGoogle Scholar
  49. Kramp P, Rafaelson OJ (1978) Delirium tremens: a double-blind comparison of diazepam and barbital treatment. Acta Psychiatr Scand 58:174–190PubMedCrossRefGoogle Scholar
  50. Kulkarni SK, Ticku MK (1989) Rol5–4513 but not FG-7142 reverses anticonvulsant effects of ethanol against bicuculline- and picrotoxin-induced convulsions in rats. Pharmacol Biochem Behav 32:233–240PubMedCrossRefGoogle Scholar
  51. Kulkarni SK, Mehta AK, Ticku MK (1990) Comparison of anticonvulsant effect of ethanol against NMDA-, kainic acid- and picrotoxin-induced convulsions in rats. Life Sci 46:481–487PubMedCrossRefGoogle Scholar
  52. Lehoullier PF, Ticku MK (1989) The pharmacological properties of GABA receptor-coupled chloride channels using 36Cl-influx in cultured spinal cord neurons. Brain Res 487:205–214PubMedCrossRefGoogle Scholar
  53. Leidenheimer N, McQuilkin SJ, Hanner LD, Whiting P, Harris RA (1992) Activation of protein kinase C selectively inhibits the y-aminobutyric acidA receptor: role of desensitization. Mol Pharmacol 41:1116–1123PubMedGoogle Scholar
  54. Levitan ES, Schofield PR, Burt DR, Rhee LM, Wisden W, Kohler M, Fujita N, Rodriguez HF, Stephenson A, Darlison MG, Barnard EA, Seeburg PH (1988) Structural and functional basis for GABAa receptor heterogeneity. Nature 335:76–79PubMedCrossRefGoogle Scholar
  55. Liljequist S, Engel J (1982) Effects of GABAergic agonists and antagonists on various ethanol-induced behavioral changes. Psychopharmacology 78:71–75PubMedCrossRefGoogle Scholar
  56. Liljequist S, Engel J (1984) The effects of GAB A and benzodiazepine receptor antagonists on the anticonflict actions of diazepam or ethanol. Pharmacol Biochem Behav 21:521–525PubMedCrossRefGoogle Scholar
  57. Liljequist S, Culp S, Tabakoff B (1986) Effect of ethanol on the binding of [35S]t-butylbicyclophosphorothionate to mouse brain membranes. Life Sci 38: 1931–1939PubMedCrossRefGoogle Scholar
  58. Lin AM-Y, Freund RK, Palmer MR (1991) Ethanol potentiation of GABA-induced electrophysiological responses in cerebellum requirement of catecholamine modulation. Neurosci Lett 122:154–158PubMedCrossRefGoogle Scholar
  59. Lister RG (1987) The benzodiazepine receptor inverse agonists FG-7142 and Rol5-4513 both reverse some of the behavioral effects of ethanol in a holeboard test. Life Sci 41:1481–1489PubMedCrossRefGoogle Scholar
  60. Lister RG, Karanian JW (1987) Rol5–4513 induces seizures in DBA/2 mice undergoing alcohol withdrawal. Alcohol 4:409–411PubMedCrossRefGoogle Scholar
  61. Maksay G, Ticku MK (1984) Characterization of GABA-benzodiazepine receptor complex by protection against inactivation by group-specific reagents. J Neuro- chem 43:261–268Google Scholar
  62. Maksay G, Ticku MK (1985) Dissociation of [35S]t-butylbicyclophosphorothionate binding differentiates convulsant and depressant drugs that modulate GABAergic transmission. J Neurochem 44:480–486PubMedCrossRefGoogle Scholar
  63. Mancillas JR, Siggins GR, Bloom FE (1986) Systemic ethanol: selective enhancement of responses to acetylcholine and somatostatin in hippocampus. Science 231:161–163PubMedCrossRefGoogle Scholar
  64. Marrosu F, Carcangiu G, Passino N, Aramo S, Mereu G (1989) Antagonism of ethanol effects by Rol5–4513: an electrophysiological analysis. Synapse 3: 117–128PubMedCrossRefGoogle Scholar
  65. Martz A, Deitrich RA, Harris RA (1983) Behavioral evidence for the involvement of y-aminobutyric acid in the actions of ethanol. Eur J Pharmacol 89:53- 62PubMedCrossRefGoogle Scholar
  66. Mehta AK, Ticku MK (1988) Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves gamma-aminobutyric acidA-gated chloride channels. J Pharmacol Exp Ther 246:558–564PubMedGoogle Scholar
  67. Mehta AK, Ticku MK (1989a) Benzodiazepine and beta-carboline interactions with GABAa receptor-gated chloride channels in mammalian cultured spinal cord neurons. J Pharmacol Exp Ther 249:418–425PubMedGoogle Scholar
  68. Mehta AK, Ticku MK (1989b) Chronic ethanol treatment alters the behavioral effects of Rol5–4513, a partially negative ligand for benzodiazepine binding sites. Brain Res 489:93–100PubMedCrossRefGoogle Scholar
  69. Mehta AK, Ticku MK (1990) Are GABAb receptors involved in the pharmacological effects of ethanol? Eur J Pharmacol 182:473–480PubMedCrossRefGoogle Scholar
  70. Mhatre M, Ticku MK (1989) Chronic ethanol treatment selectively increases the binding of inverse agonists for benzodiazepine binding sites in cultured spinal cord neurons. J Pharmacol Exp Ther 251:164–168PubMedGoogle Scholar
  71. Mhatre M, Ticku MK (1992) Chronic ethanol administration alters GABAa receptor gene expression. Mol Pharmacol 42:415–422PubMedGoogle Scholar
  72. Mhatre M, Mehta AK, Ticku MK (1988) Chronic ethanol administration increases the binding of the benzodiazepine inverse agonist and alcohol antagonist [H]Ro 15–4513 in rat brain. Eur J Pharmacol 153:141–145PubMedCrossRefGoogle Scholar
  73. Mhatre MC, Pena G, Sieghart W, Ticku MK (1993) Antibodies specific for GABAA receptora subunits reveal that chronic alcohol treatment downregulates a- subunit expression in rat brain regions. J Neurochem 61:1620–1625PubMedCrossRefGoogle Scholar
  74. Mohler H, Sieghart W, Richards JG, Hunkeler W (1984) Photo-affinity labeling of benzodiazepine receptors with a partial inverse agonist. Eur J Pharmacol 102: 191–192PubMedCrossRefGoogle Scholar
  75. Montpied P, Morrow AL, Karanian JW, Ginns EI, Martin BM, Paul SM (1991) Prolonged ethanol inhalation decreases y-aaminobutyric acidA receptor a- subunit in mRNAs in the rat cerebral cortex. Mol Pharmacol 39:157–163PubMedGoogle Scholar
  76. Morrow AL, Suzdak PD, Karanian JW, Paul SM (1988) Chronic ethanol administration alters GAB A, pentobarbital and ethanol mediated 36C1 - uptake in cerebral cortical synaptoneurosomes. J Pharmacol Exp Ther 246:158–164PubMedGoogle Scholar
  77. Nestoros JN (1980) Ethanol specifically potentiates GABA mediated neurotransmission in feline cerebral cortex. Science 209:708–710PubMedCrossRefGoogle Scholar
  78. Nishio M, Narahashi T (1990) Ethanol enhancement of GABA-activated chloride current in rat dorsal root ganglion neurons. Brain Res 518:283–286PubMedCrossRefGoogle Scholar
  79. Nutt DJ, Adinoff B, Linnoila M (1989) Benzodiazepines in the treatment of alcoholism. Recent Dev Alcohol 7:283–313PubMedGoogle Scholar
  80. Olsen RW (1982) Drug interactions at the GABA receptor ionophore complex. Ann Rev Pharmacol Toxicol 22:245–277CrossRefGoogle Scholar
  81. Olsen RW, Tobin AJ (1990) Molecular biology of GABAa receptors. FASEB J 4:1469–1480PubMedGoogle Scholar
  82. Palmer MR, van Home CG, Harlan JT, Moore EA (1988) Antagonism of ethanol effects on cerebellar purkinje neurones by the benzodiazepine inverse agonists Rol5–4513 and FG 7142. J Pharmacol Exp Ther 247:1018–1024PubMedGoogle Scholar
  83. Pole P (1985) Interactions of partial inverse benzodiazepine agonists Rol5–4513 and FG 7142 with ethanol in rats and cats. Br J Pharmacol 86:465PGoogle Scholar
  84. Pritchett DB, Sontheimer H, Shivers BD, Ymer S, Kettenmann H, Schofield PR, Seeburg PH (1989) Importance of a novel GABAa receptor subunit for benzodiazepine pharmacology. Nature 338:582–585PubMedCrossRefGoogle Scholar
  85. Ramanjaneyulu R, Ticku MK (1984) Binding characteristics and interaction of depressant drugs with [35S]t-butylbicyclophosphorothionate, a ligand that binds to the picrotoxinin site. J Neurochem 42:221–229PubMedCrossRefGoogle Scholar
  86. Rastogi SK, Ticku MK (1986) Anticonvulsant profile of drugs which facilitate GABAergic transmission on convulsions mediated by a GABAergic mechanism. Neuropharmacology 25:175–185PubMedCrossRefGoogle Scholar
  87. Rastogi SK, Thyagarajan R, Clothier J, Ticku MK (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. Neuropharmacology 25:1179–1184PubMedCrossRefGoogle Scholar
  88. Reggiani A, Barbaccia MK, Spano PF, Trabucchi M (1980) Acute and chronic ethanol treatment on specific [3H]GABA binding in different rat brain areas. Psychopharmacology 67:261–264PubMedCrossRefGoogle Scholar
  89. Rottenberg H (1985) Alcohol modulation of benzodiazepine receptors. Alcohol 2:203–207PubMedCrossRefGoogle Scholar
  90. Roy A, DeJong J, Ferraro T, Adinoff B, Ravitz B, Linnoila M (1990) CSF y- aminobutyric acid in alcoholics and control subjects. Am J Psychiatry 147: 1294–1296PubMedGoogle Scholar
  91. Samson HH, Tolliver GA, Pfeffer AO, Sadeghi KG, Mills FG (1987) Oral ethanol reinforcement in the rat: effect of the partial inverse benzodiazepine agonist Rol5–4513. Pharmacol Biochem Behav 27:517–519PubMedCrossRefGoogle Scholar
  92. Schoemaker H, Smith TL, Yamamura HI (1983) Effect of chronic ethanol consumption on central and peripheral type benzodiazepine binding sites in the mouse brain. Brain Res 258:347–350PubMedCrossRefGoogle Scholar
  93. Schofield PR, Darlison MG, Fujita N, Burt DR, Stephenson FA, Rodriguez H, Rhee LM, Ramachandran J, Reale V, Glencorse TA, Seeburg PH, Barnard EA (1987) Sequence and functional expression of the GABAa receptor shows a ligand-gated receptor super-family. Nature 328:221–227PubMedCrossRefGoogle Scholar
  94. Sieghart W, Eichinger A, Richards JG, Mohler H (1987) Photo-affinity labeling of benzodiazepine receptor proteins with the partial inverse agonists [3H]Rol5- 4513: a biochemical and autoradiographic study. J Neurochem 48:46–52PubMedCrossRefGoogle Scholar
  95. Sigel E, Baur R (1988) Activation of protein kinase C differentially modulates neuronal Na+, Ca++ and y-aminobutyric acid type A channel. Proc Natl Acad Sci USA 85:6192–6196PubMedCrossRefGoogle Scholar
  96. Sigel E, Baur R, Trube G, Mohler H, Malherbe P (1990) The effect of subunit composition of rat brain GABAa receptors on channel function. Neuron 5: 703–711PubMedCrossRefGoogle Scholar
  97. Siggins GR, Pittman QJ, French ED (1987) Effects of ethanol on CA1 and CA3 pyramidal cells in the hippocampal slice preparation: an intracellular study. Brain Res 414:22–34PubMedCrossRefGoogle Scholar
  98. Squires RF, Casida JE, Richardson M, Saederup E (1983) [35S]t-Butylbicyclo- phosphorothionate binds with high affinity to brain sites coupled to the y- aminobutyric acidA and ion recognition sites. Mol Pharmacol 23:326–336PubMedGoogle Scholar
  99. Suzdak PD, Schwartz RD, Skolnick P, Paul SM (1986a) Ethanol stimulates gamma- aminobutyric acid receptor-mediated chloride transport in rat brain synapto- neurosomes. Proc Natl Acad Sci USA 83:4071–4075PubMedCrossRefGoogle Scholar
  100. Suzdak PD, Glowa JR, Crawley JN, Schwartz RD, Skolnick P, Paul SM (1986b) A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science 234: 1243–1247PubMedCrossRefGoogle Scholar
  101. Taberner PV, Unwin JW (1981) Behavioral effects of muscimol, amphetamine and chlorpromazine on ethanol tolerant mice. Br J Pharmacol 74.276PGoogle Scholar
  102. Takada R, Saito K, Matsura H, Inoki R (1989) Effect of ethanol on hippocampal receptors in the rat brain. Alcohol 6:115–119PubMedCrossRefGoogle Scholar
  103. Tamborsky E, Marangos PJ (1986) Brain benzodiazepine binding sites in ethanol dependent and withdrawal states. Life Sci 38:465–472CrossRefGoogle Scholar
  104. Thompson WL (1978) Management of alcohol withdrawal syndromes. Arch Intern Med 138:278–283PubMedCrossRefGoogle Scholar
  105. Ticku MK (1980) The effects of acute and chronic ethanol administration and its withdrawal on y-aminobutyric acid receptor binding in rat brain. Br J Pharmacol 70:403–410PubMedGoogle Scholar
  106. Ticku MK, Burch T (1980) Alterations in GABA receptor sensitivity following acute and chronic ethanol treatment. J Neurochem 34:417–423PubMedCrossRefGoogle Scholar
  107. Ticku MK, Mhatre M (1991) Chronic ethanol administration induces changes in GABAa receptor gene expression. Neurosci Abstr 17:263(#109.7)Google Scholar
  108. Ticku MK, Rastogi SK (1980) Barbiturate-sensitive sites in the benzodiazepine- GABA receptor-ionophore complex. In: Roth SH, Miller WK (eds) Molecular and cellular mechanisms of anesthetics. Plenum, New York, pp 179–188Google Scholar
  109. Ticku MK, Burch TP, Davis WC (1983) The interaction of ethanol with the benzodiazepine ABA receptor-ionophore complex. Pharmacol Biochem Behav 18: 15–18PubMedCrossRefGoogle Scholar
  110. Ticku MK, Lowrimore P, Lehoullier P (1986) Ethanol enhances GABA-induced 36Cl-influx in primary spinal cord cultured neurons. Brain Res Bull 17:123–126PubMedCrossRefGoogle Scholar
  111. Tran VT, Snyder SH, Major LF, Hawley RJ (1981) GABA receptors are increased in brains of alcoholics. Ann Neurol 9:289–292PubMedCrossRefGoogle Scholar
  112. Turner DM, Sapp DW, Olsen RW (1991) The benzodiazepine/alcohol antagonist Rol5–4513: binding to a GABAa receptor subtype that is insensitive to diazepam. J Pharmacol Exp Ther 257:1236–1242PubMedGoogle Scholar
  113. Unwin JW, Taberner PV (1980) Sex and strain differences in GABA receptor binding after chronic ethanol drinking in mice. Neuropharmacology 19: 1257–1259PubMedCrossRefGoogle Scholar
  114. Volicer L, Biagioni TM (1982) Effect of ethanol administration and withdrawal on benzodiazepine receptor binding in the rat brain. Neuropharmacology 21: 283–286PubMedCrossRefGoogle Scholar
  115. Wafford KA, Burnett DM, Dunwiddie TV, Harris RA (1990) Genetic differences in the ethanol sensitivity of GABAa receptors expressed in Xenopus oocytes. Science 249:291–293PubMedCrossRefGoogle Scholar
  116. Wafford KA, Burnett DM, Leidenheimer NJ, Burt DR, Wang JB, Kofuji P, Dunwiddie TV, Harris RA, Sikela JM (1991) Ethanol sensitivity of the GABAA receptor expressed in Xenopus oocytes requires 8 amino acids contained in the y2L subunit. Neuron 7:27–33PubMedCrossRefGoogle Scholar
  117. White G, Lovinger DM, Weight FF (1990) Ethanol inhibits NMDA-activated current but does not alter GABA-activated current in an isolated adult mammalian neuron. Brain Res 507:332–336PubMedCrossRefGoogle Scholar
  118. Whiting P, McKernan RM, Iversen LL (1990) Another mechanism for creating diversity in y-aminobutyrate type A receptors: RNA splicing directs expression of two forms of y2 subunit, one of which contains a protein kinase C phosphorylation site. Proc Natl Acad Sci USA 87:9966–9970PubMedCrossRefGoogle Scholar
  119. Wieland HA, Luddens H, Seeburg PH (1992) A single histidine in GABAa receptors is essential for benzodiazepine agonist binding. J Biol Chem 267:1426–1429PubMedGoogle Scholar
  120. Wiesner JB, Henriksen SJ, Bloom FE (1987) Ethanol enhances recurrent inhibition in the dentate gyrus of the hippocampus. Neurosci Lett 79:169–173PubMedCrossRefGoogle Scholar
  121. Wilson JR, Plomin R (1986) Individual differences in sensitivity and tolerance to alcohol. Soc Biol 32:162–184Google Scholar
  122. Wisden W, Morris BJ, Darlison MG, Hunt SP, Barnard EA (1988) Distinct GABAA receptor a subunit mRNAs show differential patterns of expression in bovine brain. Neuron 1:937–947PubMedCrossRefGoogle Scholar
  123. Zahniser NR, Buck KJ, Curella P, McQuilkin SJ, Wilson-Shaw D, Miller CL, Klein RL, Heidenreich KA, Keir WJ, Sikela JM, Harris RA (1992) GABAa receptor function and regional analysis of subunit mRNAs in long-sleep and short-sleep mouse brain. Mol Brain Res 14:196–206PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1995

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  • M. K. Ticku
  • A. K. Mehta

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