Alcohol use disorders and current pharmacological therapies: The role of GABAA receptors

Acta Pharmacologica Sinica

Volumn 35, Issue 8, 2014, Pages 981-993

  Liang, Jing ^a   Olsen, Richard W ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Acamprosate; Alcohol use disorders; Benzodiazepine; Disulfiram; Ethanol; GABAA receptor; Hovenia; Kudzu; Naltrexone

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; ACAMPROSATE; AMPELOPSIN; BENZODIAZEPINE DERIVATIVE; DISULFIRAM; FLAVONOID; HERBACEOUS AGENT; NALTREXONE; TOPIRAMATE; UNCLASSIFIED DRUG; ALCOHOL; DRUGS USED IN THE TREATMENT OF ADDICTION; FRUCTOSE; NARCOTIC ANTAGONIST; NEUROPROTECTIVE AGENT; PLANT MEDICINAL PRODUCT; TAURINE;

ALCOHOL ABSTINENCE; ALCOHOL ABUSE; ALCOHOL CONSUMPTION; ALCOHOL USE DISORDER; ALCOHOL WITHDRAWAL; ALCOHOLISM; COGNITION; DRINKING BEHAVIOR; HERBAL MEDICINE; HOVENIA; HUMAN; MEDICINAL PLANT; NONHUMAN; PUERARIA; REVIEW; ADVERSE EFFECTS; ANALOGS AND DERIVATIVES; ANIMAL; METABOLISM;

ALCOHOL DETERRENTS; ALCOHOL DRINKING; ALCOHOLISM; ANIMALS; BENZODIAZEPINES; DISULFIRAM; ETHANOL; FRUCTOSE; HUMANS; NALTREXONE; NARCOTIC ANTAGONISTS; NEUROPROTECTIVE AGENTS; PLANT PREPARATIONS; RECEPTORS, GABA-A; TAURINE;

EID: 84905659187     PISSN: 16714083     EISSN: 17457254     Source Type: Journal    
DOI: 10.1038/aps.2014.50     Document Type: Review

References (179)

1. WHO. Global status report on alcohol and health (2011).
2. CDC. Alcohol-attributable deaths and years of potential life lost - United States, 2001. 2004; 53; 866-70.
3. NIH/NIAAA. Alcohol across the lifespan (2007).
4. Becker H. Alcohol dependence, withdrawal, and relapse. Alcohol Research and Health NIAAA publication 2008; 31: 348-61.
5. Johnson BA. Medication treatment of different types of alcoholism. Am J Psychiatry 2010; 167: 630-9.
6. NIH/NIAAA. Helping patients who drink too much: a clinician's guide. 2008.
7. Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 2006; 295: 2003-17.
8. Mason B, Goodman A , Chabac S, Leher t P. Ef fect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation. J Psychiatr Res 2006; 40: 383-93.
9. McGovern P, Zhang J, Tang J, Zhang Z, Hall GR, Moreau RA, et al. Fermented beverages of pre- and proto-historic China. Proc Natl Acad Sci U S A 2004; 101: 17593-8.
10. Bayard M, McIntyre J, Hill KR, Woodside J Jr. Alcohol withdrawal syndrome. Am Fam Physician 2004; 69: 1443-50.
11. Hobbs W, Rall T, Verdoorn T. Hypnotics and sedatives: ethanol. In: The pharmacological basis of therapeutics, 9th edtion. 1996.
12. Paul SM. Alcohol-sensitive GABA receptors and alcohol antagonists. Proc Natl Acad Sci U S A 2006; 103: 8307-8.
13. Valenzuela CF. Alcohol and neurotransmitter interactions. Alcohol Health Res World 1997; 21: 144-8.
14. Mukherjee S, Das SK, Vaidyanathan K, Vasudevan DM. Consequences of alcohol consumption on neurotransmitters - an overview. Curr Neurovasc Res 2008; 5: 266-72.
15. Koob G, Rassnick S, Heinrichs S, Weiss F. Alcohol, the reward system and dependence. EXS 1994; 71: 103-14.
16. Koob G, Volkow N. Neurocircuitry of addiction. Neuropsychopharmacol Rev 2010; 35: 217-38.
17. Wanat M, Willuhn I, Clark J, Phillips P. Phasic dopamine release in appetitive behaviors and drug addiction. Curr Drug Abuse Rev 2009; 2: 195-213.
18. NIDA (2008) Addiction Science: From Molecules to Managed Care. http://www.drugabuse.gov/publications/addiction-science.
19. Volkow N, Wang G, Fowler J, Logan J, Hitzemann R, Ding Y, et al. Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcohol Clin Exp Res 1996; 20: 1594-8.
20. Feltenstein M, See R. The neurocircuitry of addiction: an overview. Br J Pharmacol 2008; 154: 261-74.
21. Olsen R. Extrasynaptic GABAA receptors in the nucleus accumbens are necessary for alcohol drinking. Proc Natl Acad Sci U S A 2011 108: 4699-700.
22. Noori H, Spanagel R, Hansson A. Neurocircuitry for modeling drug effects. Addict Biol 2012; 17: 827-64.
23. Nayeem N, Green T, Martin I, Barnard E. Quaternary structure of the native GABAA receptor determined by electron microscopic image analysis. J Neurochem 1994; 62: 815-8.
24. Macdonald RL, Olsen RW. GABAA receptor channels. Annu Rev Neurosci 1994; 17: 569-602.
25. Barnard EA, Skolnick P, Olsen RW, Mohler H, Sieghart W, Biggio G, et al. International union of pharmacology. XV. Subtypes of gammaaminobutyric acid A receptors: classification on the basis of subunit structure and receptor function. Pharmacol Rev 1998; 50: 291-313.
26. Olsen R, Sieghart W. International union of pharmacology. LXX. Subtypes of g-aminobutyric acid(A) receptors: classification on the basis of subunit composition, pharmacology, and function. Update. Pharmacol Rev 2008; 60: 243-60.
27. Olsen R, Sieghart W. GABAA receptors: subtypes provide diversity of function and pharmacology. Neuropharmacology 2009; 56: 141-8.
28. Weiner JL, Zhang L, Carlen PL. Guanosine phosphate analogs modulate ethanol potentiation of GABAAR-mediated synaptic currents in hippocampal CA1 neurons. Brain Res 1994; 665: 307-10.
29. Olsen R, Spigelman I. GABAA receptor plasticity in alcohol withdrawal. Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado- Escueta AV, editors. SourceJasper's basic mechanisms of the epilepsies [internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US) 2012.
30. Becker HC, Veatch LM, Diaz-Granados JL. Repeated ethanol withdrawal experience selectively alters sensitivity to different chemoconvulsant drugs in mice. Psychopharmacology (Berl) 1998; 139: 145-53.
31. Boehm S, Ponomarev I, Jennings A, Whiting P, Rosahl TW, Garrett EM, et al. γ-Aminobutyric acid A receptor subunit mutant mice: new perspectives on alcohol actions. Biochem Pharmacol 2004; 68: 1581-602.
32. Koob GF. A role for GABA mechanisms in the motivational effects of alcohol. Biochem Pharmacol 2004; 68: 1515-25.
33. Mihic S, Harris R. GABA and GABAA receptor. Alcohol Health & Research World 1997; 21: 127.
34. Lithari C, Klados M, Pappas C, Albani M, Kapoukranidou D, Kovatsi L, et al. Alcohol affects the brain's resting-state network in social drinkers. PLoS One 2012; 7: e48641.
35. Buck K. New Insight into the mechanisms of ethanol effects on GABA, receptor function and expression, and their relevance to behavior. Alcohol Clin Exp Res 1996; 20: 198A-202A.
36. Buck KJ, Finn DA. Genetic factors in addiction: QTL mapping and candidate gene studies implicate GABAergic genes in alcohol and barbiturate withdrawal in mice. Addiction 2001; 96: 139-49.
37. Davies M. The role of GABAA receptors in mediating the effects of alcohol in the central nervous system. J Psychiatry Neurosci 2003; (4): 263-74.
38. Grobin AC, Matthews DB, Devaud LL, Morrow AL. The role of GABAA receptors in the acute and chronic effects of ethanol. Psychopharmacology (Berl) 1998; 139: 2-19.
39. Kumar S, Porcu P, Werner D, Matthews D, Diaz-Granados J, Helfand R, et al. The role of GABAA receptors in the acute and chronic effects of ethanol: a decade of progress. Psychopharmacology (Berl) 2009; 205: 529-64.
40. Tobler I, Kopp C, Deboer T, Rudolph U. Diazepam-induced changes in sleep: role of the a1 GABAA receptor subtype. Proc Natl Acad Sci U S A 2001; 98: 6464-9.
41. Rudolph U, Knoflach F. Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes. Nat Rev Drug Discov 2011; 10: 685-97.
42. Hanchar HJ, Dodson PD, Olsen RW, Otis TS, Wallner M. Alcoholinduced motor impairment caused by increased extrasynaptic GABAA receptor activity. Nat Neurosci 2005; 8: 339-45.
43. Liang J, Spigelman I, Olsen RW. Tolerance to sedative/hypnotic actions of GABAergic drugs correlates with tolerance to potentiation of extrasynaptic tonic currents of alcohol-dependent rats. J Neurophysiol 2009; 102: 224-33.
44. Liang J, Cagetti E, Olsen RW, Spigelman I. Altered pharmacology of synaptic and extrasynaptic GABAA receptors on CA1 hippocampal neurons is consistent with subunit changes in a model of alcohol withdrawal and dependence. J Pharmacol Exp Ther 2004; 310: 1234-45.
45. Kang M, Spigelman I, Sapp DW, Olsen RW. Persistent reduction of GABAA receptor-mediated inhibition in rat hippocampus after chronic intermittent ethanol treatment. Brain Res 1996; 709: 221-8.
46. Cagetti E, Liang J, Spigelman I, Olsen RW. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol 2003; 63: 53-64.
47. Soyka M, Preuss M, Hesselbrock V, Zill P, Koller, Bondy B. GABA-A2 receptor subunit gene (GABRA2) polymorphisms and risk for alcohol dependence. J Psychiatr Res 2008; 42: 184-91.
48. Ittiwut C, Yang B, Kranzler H, Anton R, Hirunsatit R, Weiss R, et al. GABRG1 and GABRA2 variation associated with alcohol dependence in African Americans. Alcohol Clin Exp Res 2012; 36: 588-93.
49. Edenberg H, Dick D, Xuei X, Tian H, Almasy L, Bauer L, et al. Variations in GABRA2, encoding the α2 subunit of the GABAA receptor, are associated with alcohol dependence and with brain oscillations. Am J Hum Genet 2004; 74: 705-14.
50. Enoch M. The role of GABAA receptors in the development of alcoholism. Pharmacol Biochem Behav 2008; 90: 95-104.
51. Parsian A, Zhang Z. Human chromosomes 11p15 and 4p12 and alcohol dependence: possible association with the GABRB1 gene. Am J Med Genet 1999; 88: 533-8.
52. Anstee QM, Knapp S, Maguire EP, Hosie AM, Thomas P, Mortensen M, et al. Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition. Nat Commun 2013; 4: 2816.
53. Heinz A, Goldman D, Gallinat J, Schumann G, Puls I. Pharmacogenetic insights to monoaminergic dysfunction in alcohol dependence. Psychopharmacology 2004; 174: 561-70.
54. Staley J, Gottschalk C, Petrakis I, Gueorguieva R, O'Malley S, Baldwin R, et al. Cortical γ-aminobutyric acid type A-benzodiazepine receptors in recovery from alcohol dependence: relationship to features of alcohol dependence and cigarette smoking. Arch Gen Psychiatry 2005; 62: 877-88.
55. Roh S, Matsushita S, Hara S, Maesato H, Matsui T, Suzuki G, et al. Role of GABRA2 in moderating subjective responses to alcohol. Alcohol Clin Exp Res 2011; 35: 400-7.
56. Morrow AL, Montpied P, Lingford-Hughes A, Paul SM. Chronic ethanol and pentobarbital administration in the rat: effects on GABAA receptor function and expression in brain. Alcohol 1990; 7: 237-44.
57. Wallner M, Olsen R. Physiology and pharmacology of alcohol: the imidazobenzodiazepine alcohol antagonist site on subtypes of GABAA receptors as an opportunity for drug development? Br J Pharmacol 2008; 154: 288-98.
58. Jacob T, Moss S, Jurd R. GABAA receptor trafficking and its role in the dynamic modulation of neuronal inhibition. Nat Rev Neurosci 2008; 9: 331-43.
59. Vithlani M, Moss S. The role of GABAAR phosphorylation in the con struction of inhibitory synapses and the efficacy of neuronal inhibition. Biochem Soc Trans 2009; 37: 1355-8.
60. Sieghart W, Fuchs K, Tretter V, Ebert V, Jechlinger M, Höger H, et al. Structure and subunit composition of GABAA receptors. Neurochem Int 1999; 34: 379-85.
61. Tretter V, Ehya N, Fuchs K, Sieghart W. Stoichiometry and assembly of a recombinant GABAA receptor subtype. J Neurosci 1997; 17: 2728-37.
62. Mody I. Distinguishing between GABAA receptors responsible for tonic and phasic conductances. Neurochem Res 2001; 26: 907-13.
63. Liang J, Zhang N, Cagetti E, Houser CR, Olsen RW, Spigelman I. Chronic intermittent ethanol-induced switch of ethanol actions from extrasynaptic to synaptic hippocampal GABAA receptors. J Neurosci 2006; 26: 1749-58.
64. Santhakumar V, Hanchar H, Wallner M, Olsen R, Otis T. Contributions of the GABAA receptor α6 subunit to phasic and tonic inhibition revealed by a naturally occurring polymorphism in the α6 gene. 2006; 26: 3357-64.
65. Wei W, Zhang N, Peng Z, Houser CR, Mody I. Perisynaptic localization of δ subunit-containing GABAA receptors and their activation by GABA spillover in the mouse dentate gyrus. J Neurosci 2003; 23: 10650-61.
66. Tossman U, Jonsson G, Ungerstedt U. Regional distribution and extracellular levels of amino acids in rat central nervous system. Acta Physiol Scand 1986; 127: 533-45.
67. Kittler JT, Delmas P, Jovanovic JN, Brown DA, Smart TG, Moss SJ. Constitutive endocytosis of GABAA receptors by an association with the adaptin AP2 complex modulates inhibitory synaptic currents in hippocampal neurons. J Neurosci 2000; 20: 7972-7.
68. Liang J, Suryanarayanan A, Abriam A, Snyder B, Olsen RW, Spigelman I. Mechanisms of reversible GABAA receptor plasticity after ethanol intoxication. J Neuroscience 2007; 27: 12367-77.
69. Silberman Y, Ariwodola OJ, Weiner JL. β1-Adrenoceptor activation is required for ethanol enhancement of lateral paracapsular GABAergic synapses in the rat basolateral amygdala. J Pharmacol Exp Ther 2012; 343: 451-9.
70. Suzdak PD, Schwartz RD, Skolnick P, Paul SM. Ethanol stimulates γ-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes. Proc Natl Acad Sci U S A 1986; 83: 4071-5.
71. Harris R, Allan A. Alcohol intoxication: ion channels and genetics. FASEB 1989; 3: 1689-95.
72. Gonzalez C, Moss S, Olsen R. Ethanol promotes clathrin adaptormediated endocytosis via the intracellular domain of δ-containing GABAA receptors. J Neurosci 2012; 32: 17874-81.
73. Steffensen S, Walton C, Hansen D, Yorgason J, Gallegos R, Criado J. Contingent and non-contingent effects of low-dose ethanol on GABA neuron activity in the ventral tegmental area. Pharmacol Biochem Behav 2009; 92: 68-75.
74. Chau P, Höifödt-Lidö H, Löf E, Söderpalm B, Ericson M. Glycine receptors in the nucleus accumbens involved in the ethanol intakereducing effect of acamprosate. Alcohol Clin Exp Res 2010; 34: 39-45.
75. Rewal M, Donahue R, Gill T, Nie H, Ron D, Janak P. α4 subunitcontaining GABAA receptors in the accumbens shell contribute to the reinforcing effects of alcohol. Addict Biol 2012; 17: 309-21.
76. Li J, Bian W, Dave V, Ye J. Blockade of GABAA receptors in the paraventricular nucleus of the hypothalamus attenuates voluntary ethanol intake and activates the hypothalamic-pituitary-adrenocortical axis. Addict Biol 2011; 16: 600-14.
77. Sanna E, Talani G, Obili N, Mascia M, Mostallino M, Secci PP, et al. Voluntary ethanol consumption induced by social isolation reverses the increase of α4/δ GABAA receptor gene expression and function in the hippocampus of C57BL/6J Mice. Front Neurosci 2011; 5: 15.
78. Pisu M, Mostallino M, Dore R, Maciocco E, Secci P, Serra M. Effects of voluntary ethanol consumption on emotional state and stress responsiveness in socially isolated rats. Eur Neuropsychopharmacol 2011; 21: 414-25.
79. Wallner M, Hanchar HJ, Olsen RW. Ethanol enhances α4β3δ and α6β3δ γ-aminobutyric acid type A receptors at low concentrations known to affect humans. Proc Natl Acad Sci U S A 2003; 100: 15218-23.
80. June H, Murphy J, Hewitt R, Greene T, Lin M, Mellor-Burke J, et al. Benzodiazepine receptor ligands with different intrinsic efficacies alter ethanol intake in alcohol-nonpreferring (NP) rats. Neuropsychopharmacology 1996; 14: 55-66.
81. June H, Harvey S, Foster K, McKay PF, Cummings R, Garcia M, et al. GABAA receptors containing α5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors: an extended ethanol reward circuitry. J Neurosci 2001; 21: 2166-77.
82. Mihalek RM, Bowers BJ, Wehner JM, Kralic JE, VanDoren MJ, Morrow AL, et al. GABAA-receptor δ subunit knockout mice have multiple defects in behavioral responses to ethanol. Alcohol Clin Exp Res 2001; 25: 1708-18.
83. Stephens D, Pistovcakova J, Worthing L, Atack J, Dawson G. Role of GABAA α5-containing receptors in ethanol reward: the effects of targeted gene deletion, and a selective inverse agonist. Eur J Pharmacol 2005; 526: 240-50.
84. Choi D, Wei W, Deitchman J, Kharazia V, Lesscher HM, McMahon T, et al. Protein kinase Cdelta regulates ethanol intoxication and enhancement of GABA-stimulated tonic current. J Neurosci 2008; 28: 11890-9.
85. Kokka N, Sapp DW, Taylor AM, Olsen RW. The kindling model of alcohol dependence: similar persistent reduction in seizure threshold to pentylenetetrazol in animals receiving chronic ethanol or chronic pentylenetetrazol. Alcohol Clin Exp Res 1993; 17: 525-31.
86. Cagetti E, Pinna G, Guidotti A, Baicy K, Olsen RW. Chronic intermittent ethanol (CIE) administration in rats decreases levels of neurosteroids in hippocampus, accompanied by altered behavioral responses to neurosteroids and memory function. Neuropharmacology 2004; 46: 570-9.
87. Kumar S, Kralic JE, O'Buckley TK, Grobin AC, Morrow AL. Chronic ethanol consumption enhances internalization of alpha1 subunitcontaining GABAA receptors in cerebral cortex. J Neurochem 2003; 86: 700-8.
88. Papadeas S, Grobin AC, Morrow AL. Chronic ethanol consumption differentially alters GABAA receptor α1 and α4 subunit peptide expression and GABAA receptor-mediated 36 Cl(-) uptake in mesocorticolimbic regions of rat brain. Alcohol Clin Exp Res 2001; 25: 1270-5.
89. NIH (2014) Gabra4 γ-aminobutyric acid GABAA receptor, subunit α4 [Mus musculus (house mouse)] http://wwwncbinlmnihgov/gene/140675.
90. Gilpin N, Karanikas C, Richardson H. Adolescent binge drinking leads to changes in alcohol drinking, anxiety, and amygdalar corticotropin releasing factor cells in adulthood in male rats. PLoS One 2012; 7: e31466.
91. Overstreet D, Knapp D, Breese G. Drug challenges reveal differences in mediation of stress facilitation of voluntary alcohol drinking and withdrawal-induced anxiety in alcohol-preferring P rats. Alcohol Clin Exp Res 2007; 31: 1473-81.
92. Bahi A. Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psycho social stress. Stress 2013; 16: 441-51.
93. Glue P, Nutt D. Overexcitement and disinhibition. Dynamic neurotransmitter interactions in alcohol withdrawal. Br J Psychiatry 1990; 157: 491-9.
94. Adinoff B. The alcohol withdrawal syndrome: neurobiology of treatment and toxicity. Am J Addict 1994; 3: 277-88.
95. Heinz A, Schmidt K, Baum S, Kuhn S, Dufeu P, Schmidt L, et al. Influence of dopaminergic transmission on severity of withdrawal syndrome in alcoholism. J Stud Alcohol 1996; 57: 471-4.
96. Weiss F, Parsons L, Schulteis G, Hyytiä P, Lorang M, Bloom F, et al. Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J Neurosci 1996; 16: 3474-85.
97. Clapp P, Bhave S, Hoffman P. How adaptation of the brain to alcohol leads to dependence: a pharmacological perspective. Alcohol Res Health 2008; 31: 310-39.
98. Heinz A, Ragan P, Jones D, Hommer D, Williams W, Knable MB, et al. Reduced central serotonin transporters in alcoholism. Am J Psychiatry 1998; 155: 1544-9.
99. Koob G. Neurobiology of addiction. Toward the development of new therapies. Ann N Y Acad Sci 2000; 909: 170-85.
100. Diana M, Brodie M, Muntoni A, Puddu M, Pillolla G, Steffensen S, et al. Enduring effects of chronic ethanol in the CNS: basis for alcoholism. Alcohol Clin Exp Res 2003; 27: 354-61.
101. Foster K, McKay P, Seyoum R, Milbourne D, Yin W, Sarma P, et al. GABAA and opioid receptors of the central nucleus of the amygdala selectively regulate ethanol-maintained behaviors. Neuropsychopharmacology 2004; 29: 269-84.
102. Fleming R, Acheson S, Moore S, Wilson W, Swartzwelder H. In the rat, chronic intermittent ethanol exposure during adolescence alters the ethanol sensitivity of tonic inhibition in adulthood. Alcohol Clin Exp Res 2012; 36: 279-85.
103. Koob G. Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 1992; 13: 177-84.
104. Melis M, Spiga S, Diana M. The dopamine hypothesis of drug addiction: hypodopaminergic state. Int Rev Neurobiol 2005; 63: 101-54.
105. Fadda P, Scherma M, Fresu A, Collu M, Fratta W. Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of rat. Synapse 2003; 50: 1-6.
106. Kaun K, Azanchi R, Maung Z, Hirsh J, Heberlein U. A Drosophila model for alcohol reward. Nat Neurosci 2011; 14: 612-9.
107. Robinson B, Khurana S, Kuperman A, Atkinson N. Neural adaptation leads to cognitive ethanol dependence. Curr Biol 2012; 22: 2338-41.
108. Horner A, Gadian D, Fuentemilla L, Jentschke S, Vargha-Khadem F, Duzel E. A rapid, hippocampus-dependent, item-memory signal that initiates context memory in humans. Curr Biol 2012; 22: 2369-74.
109. Miller N, Gold M. Management of withdrawal syndromes and relapse prevention in drug and alcohol dependence. Am Fam Physician 1998; 58: 139-46.
110. Shen W. Pharmacotherapy of alcoholism: the American current status. Keio J Med 1991; 40: 9-12.
111. Ricks J, Replogle W, Cook N. FPIN's clinical inquiries. Management of alcohol withdrawal syndrome. Am Fam Physician 2010; 82: 344-7.
112. Olsen RW, McCabe RT, Wamsley JK. GABAA receptor subtypes: autoradiographic comparison of GABA, benzodiazepine, and convulsant binding sites in the rat central nervous system. J Chem Neuroanat 1990; 3: 59-76.
113. Olsen RW, Sapp DM, Bureau MH, Turner DM, Kokka N. Allosteric actions of central nervous system depressants including anesthetics on subtypes of the inhibitory γ-aminobutyric acid A receptor-chloride channel complex. Ann N Y Acad Sci 1991; 625: 145-54.
114. Ozdemir V, Bremner KE, Naranjo CA. Treatment of alcohol withdrawal syndrome. Ann Med 1994; 26: 101-5.
115. Krystal J, Cramer J, Krol W, Kirk G, Rosenheck R. Naltrexone in the treatment of alcohol dependence. N Engl J Med 2001; 354: 1734-9.
116. Miller NS. Pharmacotherapy in alcoholism. J Addict Dis 1995; 14: 23-46.
117. Neave N, Reid C, Scholey A, Thompson J, Moss M, Ayre G, et al. Dose-dependent effects of flumazenil on cognition, mood, and cardio-respiratory physiology in healthy volunteers. Br Dent J 2000; 189: 668-74.
118. NIH (2010) Alcohol Use Disorders: Treatment, Services Research, and Recovery (R01).
119. Caputo F, Bernardi M. Medications acting on the GABA system in the treatment of alcoholic patients. Curr Pharm Des 2010; 16: 2118-25.
120. Anton R, Drobes D, Voronin K, Durazo-Avizu R, Moak D. Naltrexone effects on alcohol consumption in a clinical laboratory paradigm: temporal effects of drinking. Psychopharmacology (Berl) 2004; 173: 32-40.
121. O'Malley S, Krishnan-Sarin S, Farren C, Sinha R, Kreek M. Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary-adrenocortical axis. Psychopharmacology (Berl) 2002; 160: 19-29.
122. Pettinati H, O'Brien C, Rabinowitz A, Wortman S, Oslin D, Kampman K, et al. The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking. J Clin Psychopharmacol 2006; 26: 610-25.
123. Froehlich JC, Harts J, Lumeng L. Naloxone attenuates voluntary ethanol intake in rats selectively bred for high ethanol preference. Pharmacol Biochem Behav 1991; 35: 385-90.
124. Froehlich J, Wand G. The neurobiology of ethanol-opioid interaction in ethanol reinforcement. . Alcohol Clin Exp Res 1997; 20: A181-6.
125. Froehlich JC, Badia-Elder NE, Zink RW. Contribution of the opioid system to alcohol aversion and alcohol drinking behaviour. J Pharmacol Exp Ther 1998; 287: 284-92.
126. Bouza C, Angeles M, Munoz A, Amate J. Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: A systematic review. Addiction 2004; 99: 811-28.
127. Srisurapanont M, Jarusuraisin N. Naltrexone for the treatment of alcoholism: a meta-analysis of randomized controlled trials. Int J Neuropsychopharmacol 2005; 8: 267-80.
128. Jones E, Dekker L. Opiate antagonist therapy for the pruritus of cholestasis: the avoidance of opioid withdrawal-like reactions. Gastroenterology 2000; 118: 431-2.
129. Oncken C, Van-Kirk J, Kranzler H. Adverse effects of oral naltrexone: analysis of data from two clinical trials. Psychopharmacology (Berl) 2001; 154: 397-402.
130. O'Malley SS, Rounsaville BJ, Farren C, Namkoong K, Wu R, Robinson J, et al. Initial and maintenance naltrexone treatment for alcohol dependence using primary care vs specialty care: a nested sequence of 3 randomized trials. Arch Intern Med 2003; 163: 1695-704.
131. Losekam S, Kluge I, Nittel KS, Kircher T, Konrad C. Letter to the Editor: Shopping frenzy induced by naltrexone - a paradoxical effect in bipolar disorder? Psychol Med 2013; 43: 895.
132. Sonne S, Brady K. Naltrexone for individuals with comorbid bipolar disorder and alcohol dependence. J Clin Psychopharmacol 2000; 20: 114-5.
133. Sullivan M, Nunes E. New-onset mania and psychosis following heroin detoxification and naltrexone maintenance. Am J Addict 2005; 14: 486-7.
134. Williams S. Medications for treating alcohol dependence. Am Fam Physician 2005; 9: 1775-80.
135. Mann K, Kiefer F, Spanagel R, Littleton J. Acamprosate: recent findings and future research directions. Alcohol Clin Exp Res 2008; 32: 1105-10.
136. NIH/NIAAA (2005) Prescribing Medications for Alcohol Dependence.
137. Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, et al. Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation. JAMA 2006; 295: 2003-17.
138. Maisel N, Blodgett J, Wilbourne P, Humphreys K, Finney J. Metaanalysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful? Addiction 2013; 108: 275-93.
139. Mann K. The pharmacological treatment of alcohol dependence: needs and possibilities. Review Alcohol Alcohol 1996; 1: 55-8.
140. Kiefer F, Wiedemann K. Combined therapy: what does acamprosate and naltrexone combination tell us? Alcohol Alcoholism 2004; 39: 542-7.
141. Fuller R, Gordis E. Does disulfiram have a role in alcoholism treatment today? Addiction 2004; 99: 21-4.
142. Filosto M, Tentorio M, Broglio L, Buzio S, Lazzarini C, Pasolini M, et al. Disulfiram neuropathy: two cases of distal axonopathy. Clin Toxicol (Phila) 2008; 46: 314-6.
143. Roy Chengappa KN, Schwarzman LK, Hulihan JF, Xiang J, Rosenthal NR; Clinical Affairs Product Support Study-168 Investigators. Adjunctive topiramate therapy in patients receiving a mood stabilizer for bipolar I disorder: a randomized, placebo-controlled trial. J Clin Psychiatry 2006; 67: 1698-706.
144. O'Malley S, O'Connor P. Medications for unhealthy alcohol use: across the spectrum. Alcohol Res Health 2011; 33: 300-12.
145. Kushner S, Han D, Oscar-Berman M, William Downs B, Madigan M, Giordano J, et al. Declinol, a complex containing Kudzu, Bitter Herbs (Gentian, Tangerine Peel) and Bupleurum, significantly reduced alcohol use disorders identification test (AUDIT) scores in moderate to heavy drinkers: a pilot study. J Addict Res Ther 2013; 4: 153.
146. Lieber CS. Alcohol and the liver: gastroenterology 1994; 106: 1085-105.
147. McGregor N. Pueraria lobata (Kudzu root) hangover remedies and acetaldehyde-associated neoplasm risk. Alcohol 2007; 41: 469-78.
148. Bracken B, Penetar D, Maclean R, Lukas S. Kudzu root extract does not perturb the sleep/wake cycle of moderate drinkers. J Altern Complement Med 2011; 17: 961-6.
149. Ohshima Y, Okuyama T, Takahashi K, Takizawa T, Shibata S. Isolation and high performance liquid chromatography (HPLC) of isoflavonoids from the Pueraria root. Planta Med 1988; 54: 250-4.
150. Benlhabib E, Baker J, Keyler D, Singh A. Kudzu root extract suppresses voluntary alcohol intake and alcohol withdrawal symptoms in P rats receiving free access to water and alcohol. J Med Food 2004; 7: 168-79.
151. Lin R, Guthrie S, Xie C, Mai K, Lee D, Lumeng L, et al. Isoflavonoid compounds extracted from Pueraria lobata suppress alcohol preference in a pharmacogenetic rat model of alcoholism. Alcohol Clin Exp Res 1996; 20: 659-63.
152. Lin RC, Li TK. Effects of isoflavones on alcohol pharmacokinetics and alcohol-drinking behavior in rats. Am J Clin Nutr 1998; 68: 1512S-5S.
153. Shebek J, Rindone J. A pilot study exploring the effect of kudzu root on the drinking habits of patients with chronic alcoholism. J Altern Complement Med 2000; 6: 45-8.
154. Penetar D, Toto L, Farmer S, Lee D, Ma Z, Liu Y, et al. The isoflavone puerarin reduces alcohol intake in heavy drinkers: a pilot study. Drug Alcohol Depend 2012; 126: 251-6.
155. Hase K, Ohsugi M, Xiong Q, Basnet P, Kadota S, Namba T. Hepatoprotective effect of Hovenia dulcis THUNB. on experimental liver injuries induced by carbon tetrachloride or D-galactosamine/lipopolysaccharide. Biol Pharm Bull 1997; 20: 381-5.
156. Ji Y, Li J, Yang P. Effects of fruits of Hovenia dulcis Thunb on acute alcohol toxicity in mice. Zhong Yao Cai 2001; 24: 126-8.
157. Ji Y, Chen S, Zhang K, Wang W. Effects of Hovenia dulcis Thunb on blood sugar and hepatic glycogen in diabetic mice. Zhong Yao Cai 2002; 25: 190-1.
158. Liu X, Zhnag H, Wang F. Effect of Hovenia dulcis extract on expression of MMP-13 and TIMP-1 in hepatic tissue. Zhongguo Zhong Yao Za Zhi 2006; 31: 1097-100.
159. Fang H, Lin H, Chan M, Lin W, Lin W. Treatment of chronic liver injuries in mice by oral administration of ethanolic extract of the fruit of Hovenia dulcis. Am J Chin Med 2007; 35: 693-703.
160. Sakai K, Yamane T, Saitoh Y. Effect of water extracts of crude drugs in decreasing blood ethanol concentrations in rats. Chem Pharm Bull (Tokyo) 1987; 35: 4597-604.
161. Yutaka O, Hisashi I, Yosio I. Effect of extracts from Hovenia dulcis Thunb. on alcohol concentration in rats and men administered alcohol. Jpn Nutr Crop Sci Bull 1995; 48: 167-72.
162. Wang Y, Han Y, Qian J. Experimental study on antilipoperoxidation of Hovenia dulcis Thunb. China Trad Herbal Drugs 1994; 25: 306-7.
163. Kim K, Chung Y, Lee J. Hepatic detoxification activity and reduction of serum alcohol concentration of Hovenia dulcis Thunb from Korea and China. Korean J Med Crop Sci 2000; 8: 225-33.
164. Ji Y, Yang P, Li J. Preventive effect of Hovenia dulcis Thunb on alcohol-induced liver injury. Pharmacol Clinics Chin Mat Med 2000; 6: 9-20.
165. Xu B, Zheng Y, Sung C. Natural medicines for alcoholism treatment: a review. Drug Alcohol Rev 2005; 24: 525-36.
166. Li G, Min BS, Zheng C, Lee J, Oh SR, Ahn KS, et al. Neuroprotective and free radical scavenging activities of phenolic compounds from Hovenia dulcis. Arch Pharm Res 2005; 28: 804-9.
167. Sun F, Zheng XY, Ye J, Wu T, Wang J, Chen W. Potential anticancer activity of myricetin in human T24 bladder cancer cells both in vitro and in vivo. Nutr Cancer 2012; 64: 599-606.
168. Lee K, Kang N, Rogozin EA. Myricetin is a novel natural inhibitor of neoplastic cell transformation and MEK1. Carcinogenesis 2007; 28: 1918-27.
169. Li C, Lim SC, Kim J, Choi JS. Effects of myricetin, an anticancer compound, on the bioavailability and pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats. Eur J Drug Metab Pharmacokinet 2011; 36: 175-82.
170. Zheng S, Li Y, Jiang D, Zhao J, Ge J. Anticancer effect and apoptosis induction by quercetin in the human lung cancer cell line A-549. Mol Med Rep 2012; 5: 822-6.
171. Chen X. Protective effects of quercetin on liver injury induced by ethanol. Pharmacogn Mag 2010; 6: 135-41.
172. Thiyagarajah P, Kuttan SC, Lim SC, Teo TS, Das NP. Effect of myricetin and other flavonoids on the liver plasma membrane Ca2+ pump. Kinetics and structure-function relationships. Biochem Pharmacol 1991; 41: 669-75.
173. Li Y, Ding Y. Minireview: Therapeutic potential of myricetin in diabetes mellitus. Food Sci Human Wellness 2012; 1: 19-25.
174. Mahmoud M, Hassan N, El Bassossy H, Fahmy A. Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: effect on low grade inflammation. PLoS One 2013; 8: e63784.
175. NIAAA (2012) NIAAA Director's Report on Institute Activities to the 130th Meeting of the National Advisory Council on Alcohol Abuse and Alcoholism - Animal study finds that dihydromyricetin blocks alcohol intoxication.
176. Ma Z, Wang J, Jiang H, Liu T, Xie J. Myricetin reduces 6-hydroxydopamine- induced dopamine neuron degeneration in rats. Neuroreport 2007; 18: 1181-5.
177. Prasad J, Baitharu I, Sharma A, Dutta R, Prasad D, Singh S. Quercetin reverses hypobaric hypoxia-induced hippocampal neurodegeneration and improves memory function in the rat. High Alt Med Biol 2013; 14: 383-94.
178. Shen Y, Lindemeyer AK, Gonzalez C, Shao XM, Spigelman I, Olsen RW, et al. Dihydromyricetin as a novel anti-alcohol intoxication medication. J Neurosci 2012; 32: 390-401.
179. Davies D, Bortolato M, Finn D, Ramaker M, Barak S, Ron D, et al. Recent advances in the discovery and preclinical testing of novel compounds for the prevention and/or treatment of alcohol use disorders. Alcohol Clin Exp Res 2013; 37: 8-15.