Clinical Application of Findings from Animal Research on Alcohol Self-Administration and Dependence

  • M. K. Romach
  • D. M. Tomkins
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 114)

Overview

Preceding chapters have reviewed progress made in the understanding of the basic mechanisms of action of alcohol and preclinical evidence suggesting the involvement of a number of neurotransmitter and neuropeptide systems in the modulation of ethanol1 self-administration, dependence, and tolerance. The aim of this chapter is to integrate some of these experimental findings with the clinical manifestations of alcohol abuse and dependence and to discuss their application to the development of pharmacotherapies for treatment of these disorders. It is impossible to review all the important research developments of the past several years, and we will therefore focus on those areas with direct and current relevance to the management of alcoholism. In particular, self-administration studies and their pharmacologic manipulation will be emphasized.

Since the ideal initial requirement for clinical studies of medications to alter alcohol consumption is that there should be extensive preclinical pharmacology with the compounds, we will selectively review those drugs which have been systematically evaluated preclinically and as a result showed clinical promise. The ensuing clinical work will then be described. In addition, several issues are emerging with important clinical implications, for example, comorbid psychiatric disorders in alcohol abusers. They underscore the need for new approaches to investigate clinically driven concepts in laboratory animals. These will be reviewed briefly.

Keywords

Depression Morphine Serotonin Carbamazepine Clonidine 

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References

  1. Altshuler HL, Phillips PE, Feinhandler DA (1980) Alteration of ethanol self-administration by naltrexone. Life Sci 26:679–688PubMedGoogle Scholar
  2. Annis HM (1982) Inventory of drinking situations (IDS-100). Addiction Research Foundation, TorontoGoogle Scholar
  3. Annis HM, Davis CS (1989) Relapse prevention. In: Hester RK, Miller WR (eds) Handbook of alcoholism treatment approaches. Pergamon, New York, pp 170–182Google Scholar
  4. Azrin NH, Sisson RW, Meyers R, Godley M (1982) Alcoholism treatment by disulfiram and community reinforcement therapy. J Behav Ther Exp Psychiatry 13:105–112PubMedGoogle Scholar
  5. Ballenger JC, Post RM (1978) Kindling as a model for alcohol withdrawal syndromes. Br J Psychiatry 133:1–14PubMedGoogle Scholar
  6. Barnes JM, Costall B, Coughlan J, Domeney AM, Gerrard PA, Kelly ME, Naylor RJ, Tomkins DM, Tyers MB (1990) The effects of ondansetron, a 5-HT3 receptor antagonist in rodents and primates. Pharmacol Biochem Behav 35: 955–962PubMedGoogle Scholar
  7. Baumgartner GR, Rowen RC (1987) Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome. Arch Intern Med 147:1223–1226PubMedGoogle Scholar
  8. Bjertnaes A, Block JM, Hafstad PE, Holte M, Ottemo I, Larsen T, Pinder RM, Steffensen K, Stulemeijer SM (1982) A multicentre placebo-controlled trial comparing the efficacy of mianserin and chlordiazepoxide in general practice patients with primary anxiety. Acta Psychiatr Scand 66:199–207PubMedGoogle Scholar
  9. Blackburn JR, Phillips AG, Jakubovic A, Fibiger HC (1989) Dopamine and preparatory behaviour. II. A neurochemical analysis. Behav Neurosci 103:15–23PubMedGoogle Scholar
  10. Blanchard RJ, Hori K, Tom P, Blanchard DC (1987) Social structure and ethanol consumption in the laboratory rat. Pharmacol Biochem Behav 28:437–442PubMedGoogle Scholar
  11. Borg S, Kuande H, Ryberg U et al. (1982) Endorphin levels in human cerebrospinal fluid during alcohol intoxication and withdrawal. Psychopharmacology (Berl) 78:101–103Google Scholar
  12. Borg S, Kuande H, Liljeberg P et al. (1985) 5 Hydroxyindoleacetic acid in cerebrospinal fluid in alcoholic patients under different clinical conditions. Alcohol 2:415–418PubMedGoogle Scholar
  13. Borg V (1983) Bromocriptine in the prevention of alcohol abuse. Acta Psychiatr Scand 68:100–110PubMedGoogle Scholar
  14. Borg V, Weinholdt T (1982) Bromocriptine in the treatment of the alcohol withdrawal syndrome. Acta Psychiatr Scand 65:101–111PubMedGoogle Scholar
  15. Brewer C (1986) Supervised disulfiram in alcoholism. Br J Hosp Med 35:116–119PubMedGoogle Scholar
  16. Brown ME, Anton RF, Malcolm R, Ballenger JC (1988) Alcohol detoxification and withdrawal seizures: clinical support for a kindling hypothesis. Biol Psychiatry 23:507–514PubMedGoogle Scholar
  17. Bruno F (1989) Buspirone in the treatment of alcoholic patients. Psychopathology 22 [Suppl]:49–59PubMedGoogle Scholar
  18. Burroughs AK, Morgan MY, Sherlock S (1985) Double-blind controlled trial of bromocriptine, chlordiazepoxide and chlormethiazole for alcohol withdrawal symptoms. Alcohol Alcohol 20:263–271PubMedGoogle Scholar
  19. Butler D, Messiha FS (1986) Alcohol withdrawal and carbamazepine. Alcohol 3:113–129PubMedGoogle Scholar
  20. Cappell H (1975) An evaluation of tension models of alcohol consumption. In: Gibbons RJ, Israel Y, Kalant H et al. (eds) Research advances in alcohol and drug problems. Wiley, New York, pp 177–210Google Scholar
  21. Carboni E, Acquas E, Frau R, Di Chiara G (1989) Differential inhibitory effect of a 5-HT3 antagonist on drug-induced stimulation of dopamine release. Eur J Pharmacol 164:515–519PubMedGoogle Scholar
  22. Carroll ME, Lac ST, Asencio M, Klagh R (1990) Fluoxetine reduces intravenous cocaine self-administration in rats. Pharmacol Biochem Behav 35:237–244PubMedGoogle Scholar
  23. Chang KJ, Cuatrecasas P (1981) Heterogeneity and properties of opiate receptors. Fed Proc 40:2729–2734PubMedGoogle Scholar
  24. Cicero TJ (1980) Animal models of alcoholism. In: Sinclair JD, Kiianmaa K (eds) Animal models in alcohol research. Academic, New York, pp 99–117Google Scholar
  25. Collins DM, Myers RD (1987) Buspirone attenuates volitional alcohol intake in the chronically drinking monkey. Alcohol 4:49–56PubMedGoogle Scholar
  26. Cornelius JR, Fisher BW, Salloum IM, Cornelius MD, Ehler JG (1992) Fluoxetine trial in depressed alcoholics. Alcohol Clin Exp Res 16(2):362Google Scholar
  27. Costall B, Kelly ME, Naylor RJ (1988) The anxiolytic and anxiogenic actions of ethanol in a mouse model. J Pharm Pharmacol 40:197–202PubMedGoogle Scholar
  28. Costall B, Jones BJ, Kelly ME, Naylor RJ, Onaivi ES, Tyers MB (1990) Ondansetron inhibits behavioural consequence of withdrawing from drugs of abuse. Pharmacol Biochem Behav 36:339–344PubMedGoogle Scholar
  29. Cotton R, Giles MG, Miller L, Shaw JS, Timms D (1984) ICII74864: a highly selective antagonist for the opioid delta receptor. Eur J Pharmacol 97:331–332PubMedGoogle Scholar
  30. Cox BJ, Norton GR, Swinson RP, Endler NS (1990) Substance abuse and panic related anxiety: a critical review. Behav Res Ther 28:385–393PubMedGoogle Scholar
  31. Crabbe JC, Belknap JK (1992) Genetic approaches to drug dependence. Trends Pharmacol Sci 15:212–219Google Scholar
  32. Curzon G, Kennett GA (1990) m-CPP: a tool for studying behavioural responses associated with 5HT1C receptors. Trends Pharmacol Sci 11:181–182PubMedGoogle Scholar
  33. Daoust M, Saligaut C, Chadelaud M, Chretien P, Moore N, Biosmare F (1984) Attenuation by antidepressant drugs of alcohol intake in rats. Alcohol 1:379–384PubMedGoogle Scholar
  34. Di Chiara G, Imperato A (1985) Ethanol preferentially stimulates dopamine release in the nucleus accumbens of freely moving rats. Eur J Pharmacol 115:131–132PubMedGoogle Scholar
  35. Dingledine R, Hynes MA, King GL (1986) Involvement of N-methyl-D aspartate receptors in epileptiform bursting in the rat hippocampal slice. J Physiol (Lond) 380:175–189Google Scholar
  36. Dongier M, Vachon L, Schwartz G (1991) Bromocriptine in the treatment of alcohol dependence. Alcohol Clin Exp Res 15:970–977PubMedGoogle Scholar
  37. Dorus W, Ostrow DG, Anton R, Cushman P, Collins JF, Schaefer M, Charles HL, Desai P, Hayashida M, Malkerneker U, Willenbring M, Fiscella R, Sather MR (1989) Lithium treatment of depressed and nondepressed alcoholics. JAMA 262:1646–1652PubMedGoogle Scholar
  38. Dougherty RJ, Gates RR (1990) The role of buspirone in the management of alcohol withdrawal. A preliminary investigation. J Subst Abuse Treatm 7:189–192Google Scholar
  39. Edwards G, Arif A, Hodgson R (1981) Nomenclature and classification of drug and alcohol related problems: a WHO memorandum. Bull WHO 59:225–242PubMedGoogle Scholar
  40. Ellison G (1987) Stress and alcohol intake: the socio-pharmacological approach. Physiol Behav 40:378–392Google Scholar
  41. Eriksson E, Humble M (1990) Serotonin in psychiatric pathophysiology: a review of data from experimental and clinical research. In: Pohl R, Gershon S (eds) The biological basis of psychiatric treatment. Karger, Basel, pp 66–119 (Progress in basic clinical pharmacology, vol 3)Google Scholar
  42. Fadda F, Garau B, Marchei F, Colombo G, Gessa GL (1991) MDL72222, a selective 5-HT3 receptor antagonist, suppresses voluntary ethanol consumption in alcohol-preferring rats. Alcohol Alcohol 26:107–110PubMedGoogle Scholar
  43. File SE, Zharkovsky A, Hitchcott PK (1992) Effects of nitrendipine chlordiazepoxide, flumazenil and baclofen on the increased anxiety resulting from alcohol withdrawal. Prog Neuropsychopharmacol Biol Psychiatry 16:87–93PubMedGoogle Scholar
  44. Fletcher PJ, Davies M (1990) A pharmacological analysis of the eating response induced by 8-OH-DPAT injected into the dorsal raphe nucleus reveals the involvement of a dopaminergic mechanism. Psychopharmacology (Berl) 100: 188–194Google Scholar
  45. Froehlich JC, Harts J, Lumeng L, Li T-K (1988) Enkephalinergic involvement in voluntary ethanol consumption. In: Kuriyama K, Takada A, Ishii H (eds) Biomedical and social aspects of alcohol and alcoholism. Excerpta Medica, Amsterdam, pp 235–238Google Scholar
  46. Froehlich JC, Zweifel M, Harts J, Lumeng L, Li T-K (1991) Importance of delta opioid receptors in maintaining high alcohol drinking. Psychopharmacology (Berl) 103:467–472Google Scholar
  47. Fuller RK, Branchey L, Brightwell DR, Derman RM, Emrick CD, Iber FL, James KE, Lacoursiere RB, Lee KK, Lowenstam I, Maany I, Neiderhiser D, Nocks JJ, Shaw S (1986) Disulfiram treatment of alcoholism: a veterans administration cooperative study. JAMA 256:1449–1455PubMedGoogle Scholar
  48. Gauvin DV, Youngblood BD, Holloway FA (1992) The discriminative stimulus properties of acute ethanol withdrawal (hangover) in rats. Alcohol Clin Exp Res 16:336–341PubMedGoogle Scholar
  49. Genazzani AR, Nappi G, Facchinetti F, Mezzela GL, Parrini D, Sinforiani E, Petraglia F, Savoldi J (1982) Central deficiency of B-endorphin in alcohol addicts. J Clin Endocrinol Metab 55:583–586PubMedGoogle Scholar
  50. George DT, Benkelfat C, Murphy DJ, Schmitz J, Linnoila M (1990) Ethanol-like behavioural response in abstinent alcoholics infused with the 5-HT agonist mCPP. Biol Psychiatry 27:176AGoogle Scholar
  51. Gianoulakis C, de Waele JP, Kiianmaa K (1992) Differences in the brain and pituitary B-endorphin system between the alcohol-preferring AA and alcohol-avoiding ANA rats. Alcohol Clin Exp Res 16:453–459PubMedGoogle Scholar
  52. Gill K, France C, Amit Z (1986) Voluntary ethanol consumption in rats: an examination of blood/brain ethanol levels and behaviour. Alcohol Clin Exp Res 4:457–462Google Scholar
  53. Gill K, Amit Z, Koe BK (1988) Treatment with sertraline, a new serotonin uptake inhibitor, reduces voluntary ethanol consumption in rats. Alcohol 5:349–354PubMedGoogle Scholar
  54. Goldberg HL, Finnerty R (1982) Comparison of buspirone in two separate studies. J Clin Psychiatry 43:87–91PubMedGoogle Scholar
  55. Gongwer MA, Murphy JM, McBride WJ, Lumeng L, Li T-K (1989) Regional brain contents of serotonin, dopamine and their metabolites in the selectively bred high and low alcohol drinking lines of rats. Alcohol 6:317–320PubMedGoogle Scholar
  56. Gorelick DA, Paredes A (1992) Effect of fluoxetine on alcohol consumption in male alcoholics. Alcohol Clin Exp Res 16(2):261–265PubMedGoogle Scholar
  57. Goudie AJ, Emmett-Oglesby MW (eds) (1989) Psychoactive drugs: tolerance and sensitization. Humana, CliftonGoogle Scholar
  58. Grant KA, Barrett JE (1991) Blockade of the discriminative stimulus effects of ethanol with 5-HT3 receptor antagonists. Psychopharmacology (Berl) 104:451–456Google Scholar
  59. Grank KA, Colombo G (1992) Ethanol-like discriminative stimulus effects of the 5-HT, agonist TFMPP: effect of training dose. Alcohol Clin Exp Res 16:368Google Scholar
  60. Grant KA, Valverius P, Hudspith M, Tabakoff B (1990) Ethanol withdrawal seizures and the NMD A receptor complex. Eur J Pharmacol 176:289–296PubMedGoogle Scholar
  61. Griffith JD, Jasinski DR, Casten GP et al. (1986) Investigation of the abuse liability of buspirone in alcohol-dependent patients. Am J Med 80:30–35PubMedGoogle Scholar
  62. Hatsukami D, Pickens RW (1982) Post treatment depression in an alcohol and drug abuse population. Am J Psychiatry 39:1563–1566Google Scholar
  63. Henningfield JE, Meisch RA (1979) Ethanol drinking by rhesus monkeys with concurrent access to water. Pharmacol Biochem Behav 10:777–782PubMedGoogle Scholar
  64. Higgins GA, Nguyen P, Joharchi N, Sellers EM (1991) Effects of 5-HT3 receptor antagonists on behavioural measures of naloxone-precipitated opioid withdrawal. Psychopharmacology (Berl) 105:322–328Google Scholar
  65. Higgins GA, Tomkins DM, Fletcher PJ, Sellers EM (1992) Effect of drugs influencing 5-HT function on ethanol drinking behaviour in rats: studies using a drinkometer system. Neurosci Biobehav Rev 16:535–552PubMedGoogle Scholar
  66. Hilakivi-Clarke L, Lister RG (1992) Social status and voluntary alcohol consumption in mice: interaction with stress. Psychopharmacology (Berl) 10:276–282Google Scholar
  67. Hindmarsh JG, Rose S, Collins P, Jenner P (1993) Stepwise administration prevents the fenfluramine-induced depletion of brain 5-hydroxytryptamine in the rat. British Pharmacological Society, winter meeting, p 144Google Scholar
  68. Hjorth S, Sharp T (1991) Effect of the 5-HT1A receptor agonist 8-OH DPAT on the release of 5-HT in dorsal and median raphe-innervated rat brain regions as measured by in vivo microdialysis. Life Sci 48:1779–1786PubMedGoogle Scholar
  69. Hoffman PL, Rabe CS, Grant KA, Valverius P, Hudspith M, Tabakoff B (1990) Ethanol and the NMDA receptor. Alcohol 7:229–231PubMedGoogle Scholar
  70. Hubbell CL, Marglin SH, Spitalnic SJ, Abelson ML, Wild KD, Reid LD (1991) Opioidergic, serotonergic and dopaminergic manipulations and rats’ intake of a sweetened alcoholic beverage. Alcohol 8:355–367PubMedGoogle Scholar
  71. Hunt WA (1973) Changes in the neuroexcitability of alcohol dependent rats undergoing withdrawal as measured by the pentylenetetrazole seizure threshold. Neuropharmacology 12:1097–1102PubMedGoogle Scholar
  72. Hunter BE, Boast CA, Walker DW, Zornetzer SF (1973) Alcohol withdrawal syndrome in rats: neural and behavioural correlates. Pharmacol Biochem Behav 1:719–725PubMedGoogle Scholar
  73. Idemudia SO, Bhadra S, Lai H (1989) The pentylenetetrazole-like interoceptive stimulus produced by ethanol withdrawal is potentiated by bicuculline and Picrotoxin. Neuropsychopharmacology 2:115–122PubMedGoogle Scholar
  74. Jaffe J, Ciraulo D (1986) Alcoholism and depression. In: Meyer RE (ed) Psycho-pathology and addictive disorders. Guilford, New York, pp 293–320Google Scholar
  75. Jaffe JH (1992) Current concepts of addiction. In: O’Brien CP, Jaffe JH (eds) Addictive states. Raven, New York, pp 1–21Google Scholar
  76. Kahn RS, Wetzler S (1991) m-Chlorophenylpiperazine as a probe of serotonin function. Biol Psychiatry 30:1139–1166PubMedGoogle Scholar
  77. Kalant AH (1987) Current trends in biomedical research on alcohol. Alcohol Alcohol [Suppl 1]:1–12Google Scholar
  78. Kennett GA, Curzon G (1988) Evidence that mCPP may have behavioural effects mediated by central 5HT1C receptors. Br J Pharmacol 94:137PubMedGoogle Scholar
  79. Kennett GK, Whitton P, Shah K, Curzon G (1989) Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1c receptor antagonists. Eur J Pharmacol 164:445–454PubMedGoogle Scholar
  80. Kiianmaa K, Kokkonen J, Nurmi M, Nykanen I (1992) Effect of ethanol on the release of monoamines in the nucleus accumbens of the alcohol-preferring AA and alcohol avoiding ANA rats. Soc Neurosci Abstr 18:598.6Google Scholar
  81. Knapp DJ, Pohorecky LA (1992) Zacopride, a 5-HT3 receptor antagonist, reduces voluntary ethanol consumption in rats. Pharmacol Biochem Behav 41:847–850PubMedGoogle Scholar
  82. Knapp DJ, Benjamin D, Pohorecky LA (1992) Effects of gepirone on ethanol consumption, exploratory behaviour and motor performance in rats. Drug Dev Res 26:319–341Google Scholar
  83. Koob GF, Bloom FE (1988) Cellular and molecular mechanisms of drug dependence. Science 242:715–723PubMedGoogle Scholar
  84. Koob GF, Weiss F (1992) Neuropharmacology of cocaine and ethanol dependence. Recent Dev Alcohol 10:201–233PubMedGoogle Scholar
  85. Koppi S, Eberhardt G, Haller R, Konig P (1987) Calcium channel blocking agent in the treatment of acute alcohol withdrawal-caroverine versus meprobamate in a randomized double-blind study. Neuropsychobiology 17:49–52PubMedGoogle Scholar
  86. Kornet M, Goosen C, Van Ree JM (1991) Effect of naltrexone on alcohol consumption during chronic alcohol drinking and after a period of imposed abstinence in free choice drinking rhesus monkeys. Psychopharmacology (Berl) 104:367–376Google Scholar
  87. Kostowski W, Dyr W (1992) The effects of 5-HT1A receptor agonists on ethanol preference in the rat. Alcohol 9:283–286PubMedGoogle Scholar
  88. Kranzler HR, Liebowitz NR (1988) Anxiety and depression in substance abuse: clinical implications. Med Clin North Am 72:867–885PubMedGoogle Scholar
  89. Kranzler HR, Meyer RE (1989) An open trial of buspirone in alcoholics. J Clin Psychopharmacol 9(5):379–80PubMedGoogle Scholar
  90. Kranzler HR, Orrok B (1989) The pharmacotherapy of alcoholism. In: Tasman A, Hales RE, Frances A J (eds) Review of psychiatry, vol 8. American Psychiatric Association, Washington, pp 359–379Google Scholar
  91. Kranzler H, Del Boca F, Babor T (1991) Fluoxetine as an adjunct to relapse prevention in alcoholics. Annual Meeting of the American College of Neuropsychopharmacology, San Juan/Puerto RicoGoogle Scholar
  92. Kranzler H, Del Boca F, Rounsaville B (1992) Psychopathology as a predictor of outcome three years after alcoholism treatment. Alcohol Clin Exp Res 16(2):363Google Scholar
  93. Kraus ML, Gottlieb LD, Horwitz RI, Anscher M (1985) Randomized clinical trial of atenolol in patients with alcohol withdrawal. N Engl J Med 313(15):905–909PubMedGoogle Scholar
  94. Kulkosky PJ, Sanchez MR, Foderaro MA, Chiu N (1989) Cholecystokinin and satiation with alcohol. Alcohol 6:395–402PubMedGoogle Scholar
  95. Kushner MG, Sher KJ, Beitman BD (1990) The relation between alcohol problems and the anxiety disorders. Am J Psychiatry 147:685–695PubMedGoogle Scholar
  96. Lal H, Harris CM, Benjamin D, Springfield AC, Bhadra S, Emmett-Oglesby MW (1988) Characterization of a pentylenetetrazole-like interoceptive stimulus produced by ethanol withdrawal. J Pharmacol Exp Ther 247:508–518PubMedGoogle Scholar
  97. Lal H, Prather PL, Rezazadeh SM (1991) Anxiogenic behaviour in rats during acute and protracted ethanol withdrawal: reversal by buspirone. Alcohol 8:467–471PubMedGoogle Scholar
  98. Lane JD, Pickering CL, Hooper ML, Fagan K, Tyers MB, Emett-Oglesby MW (1992) Failure of ondansetron to block the discriminative or reinforcing stimulus effects of cocaine in the rat. Drug Alcohol Depend 30:151–162PubMedGoogle Scholar
  99. Lee MA, Meltzer HY (1990) Neuroendocrine responses to serotonergic agents in alcoholics. Biol Psychiatry 30(10): 1017–1030Google Scholar
  100. Linnoila M (1990) Monoamines and impulse control. In: Swinkels JA, Blijleven W (eds) Depression, anxiety and aggression: factors that influence the course. Medidact, Houten, pp 167–169Google Scholar
  101. Linseman MA (1987) Alcohol consumption in free-feeding rats: procedural, genetic and pharmacokinetic factors. Psychopharmacology (Berl) 92:254–261Google Scholar
  102. Litten RZ, Allen JP (1991) Pharmacotherapies for alcoholism: promising agents and clinical issues. Alcohol Clin Exp Res 15:620–633PubMedGoogle Scholar
  103. Little HJ, Dolin SJ, Halsey MJ (1986) Calcium channel antagonists decrease the ethanol withdrawal syndrome. Life Sci 39:2059–2065PubMedGoogle Scholar
  104. Lorens SA, Sainasti SM (1978) Naloxone blocks the excitatory effect of ethanol and chlordiazepoxide on lateral hypothalmic self-stimulation behaviour. Life Sci 23:1359–1364PubMedGoogle Scholar
  105. Lovinger DM (1991) Ethanol potentiation of 5-HT3 receptor mediated ion current in NCB-20 neuroblastoma cells. Neurosci Lett 122:57–60PubMedGoogle Scholar
  106. Ludwig AM, Stark LH (1974) Alcohol craving: subjective and situational aspects. Q J Stud Alcohol 35:899–905PubMedGoogle Scholar
  107. Malcolm R, Ballenger JC, Sturgis ET, Anton R (1989) Double-blind controlled trial comparing carbamazepine to oxazepam treatment of alcohol withdrawal. Am J Psychiatry 146(5):617–621PubMedGoogle Scholar
  108. Malcolm R, Anton RF, Randall CL, Johnston A, Brady K, Thevos A (1992) A placebo-controlled trial of buspirone in anxious inpatient alcoholics. Alcohol Clin Exp Res 16:1007–1013PubMedGoogle Scholar
  109. Marlatt GA, Gordon JR (1980) Determinants of relapse: implications for the maintenance of behaviour change. In: Davidson PO, Davidson SM (eds) Behavioural medicine: changing health lifestyles. Brunner/Mazel, New York, pp 410–452Google Scholar
  110. Mason BJ, Kocsis JH (1991) Desipramine treatment of alcoholism. Psychopharmacol Bull 27:155–161PubMedGoogle Scholar
  111. Mason BJ, Ritvo EC, Welch B, Zimmer E, Salvato F, Goldberg G (1992) Repeated measures of body weight and Hamilton depression scores in alcoholics chronically treated with Nalmefene, a new opiate antagonist. Annual Meeting of the American College of Neuropsychopharmacology, San Juan/Puerto RicoGoogle Scholar
  112. McBride WJ, Murphy JM, Lumeng L, Li T-K (1988) Effects of Rol5–4513, fluoxetine and desipramine on the intake of ethanol, water and food by the alcohol-preferring (P) and non-preferring (NP) lines of rats. Pharmacol Biochem Behav 30:1045–1050PubMedGoogle Scholar
  113. McBride WJ, Murphy JM, Lumeng L, Li T-K (1990) Serotonin, dopamine and GAB A involvement in alcohol drinking of selectively bred rats. Alcohol 7: 199–205PubMedGoogle Scholar
  114. McGrath PJ, Goldman D, Nunes EN, Quitkin FM, Stewart JM, Goldman R (1991) Imipramine treatment of depressed alcoholics. Annual Meeting of the American Psychiatric Association, San FranciscoGoogle Scholar
  115. Meert TF, Awouters F, Niemegeers CJE, Schellenkens KHL, Janssen PAJ (1991) Ritanserin reduces abuse of alcohol, cocaine and fentanyl in rats. Pharmacopsychiatry 24:159–163PubMedGoogle Scholar
  116. Mello NK (1983) A behavioural analysis of the reinforcing properties of alcohol and other drugs in man. In: Kissin B, Begleiter H (eds) The biology of alcoholism: the pathogenesis of alcoholism, vol 7. Plenum, New York, pp 133–198Google Scholar
  117. Meyer RE (1986) Anxiolytics and the alcoholic patient. J Stud Alcohol 47(4):269–273PubMedGoogle Scholar
  118. Meyer RE, Babor TF (1989) Explanatory models of alcoholism. In: Tasman A, Hales RE, Frances A J (eds) Review of psychiatry, vol 8. American Psychiatric Association, Washington, pp 273–292Google Scholar
  119. Michel MK, Bolger G, Weissman B-A (1985) Binding of a new opiate antagonist, nalmefene to rat membranes. Methods Find Exp Clin Pharmacol 7:175–177PubMedGoogle Scholar
  120. Middaugh LD, Read E, Boggan WO (1978) Effects of naloxone on ethanol induced alterations of locomotor activity in C57BL/6 mice. Pharmacol Biochem Behav 11:157–160Google Scholar
  121. Miller NS, Dackis CA, Gold MS (1987) The relationship of addiction, tolerance and dependence to alcohol and drugs: a neurochemical approach. J Subst Abuse Treatm 4:197–207Google Scholar
  122. Miller WR, Hester RK (1986) The effectiveness of alcoholism treatment-what research reveals. In: Miller WE, Heather N (eds) Treating addictive behaviours: processes of change. Plenum, New York, pp 121–174Google Scholar
  123. Monte JM, Alterwain P (1991) Ritanserin decreases alcohol intake in chronic alcoholics. Lancet 337:60Google Scholar
  124. Mullaney JA, Trippett CJ (1979) Alcohol dependence and phobias: clinical description and relevance. Br J Psychiatry 35:565–573Google Scholar
  125. Murphy DL (1990) Neuropsychiatric disorders and the multiple human brain serotonin receptor subtypes and subsystems. Neuropsychopharmacology 3: 457–471PubMedGoogle Scholar
  126. Murphy JM, Waller MB, Gatto GJ, McBride WJ, Lumeng L, Li T-K (1985) Monoamine uptake inhibitors attenuate ethanol intake in alcohol-preferring (P) rats. Alcohol 2:349–352PubMedGoogle Scholar
  127. Murphy JM, McBride WJ, Lumeng L, Li T-K (1987) Effects of serotonergic agents on ethanol intake of the high alcohol drinking (HAD) line of rats. Alcohol Clin Exp Res 11:208Google Scholar
  128. Myers MD, Quarfordt SD (1991) Alcohol drinking attenuated by sertraline in rats with 6-OH DOPA or 5,7-DHT lesions of the N-accumbens: a caloric response? Pharmacol Biochem Behav 40:923–928PubMedGoogle Scholar
  129. Myers RD, Borg S, Mossberg R (1986) Antagonism by naltrexone of voluntary alcohol selection in the chronically drinking macaque monkey. Alcohol 3:383–388PubMedGoogle Scholar
  130. Naranjo CA, Sellers EM (1989) Serotonin uptake inhibitors attenuate ethanol intake in problem drinkers. Recent Dev Alcohol 7:255–266PubMedGoogle Scholar
  131. Naranjo CA, Sellers EM, Roach CA, Woodley DV, Sanchez-Craig M, Sykora K (1984) Zimelidine-induced variations in alcohol intake by non-depressed heavy drinkers. Clin Pharmacol Ther 35:374–381PubMedGoogle Scholar
  132. Naranjo CA, Sellers EM, Sullivan JT, Woodley DV, Kadlec K, Sykora K (1987) The serotonin uptake inhibitor citalopram attenuates ethanol intake. Clin Pharmacol Ther 41:266–274PubMedGoogle Scholar
  133. Naranjo CA, Sullivan JT, Kadlec K, Woodley-Remus DV, Kennedy G, Sellers EM (1989) Differential effects of viqualine on alcohol intake and other consummatory behaviours. Clin Pharmacol Ther 46:301–309PubMedGoogle Scholar
  134. Naranjo CA, Kadlec K, Sanhueza P, Woodley-Remus DV, Sellers EM (1990) Fluoxetine differentially alters alcohol intake and other consummatory behaviours in problem drinkers. Clin Pharmacol Ther 47:490–498PubMedGoogle Scholar
  135. Naranjo CA, Poulos CX, Bremner KE, Lanctot KL (1992) Citalopram decreases desirability, liking and consumption of alcohol in alcohol dependent drinkers. Clin Pharmacol Ther 51:729–739PubMedGoogle Scholar
  136. Nunes EV, McGrath PJ, Quitkin FM, Stewart JP, Harrison W, Tricamo E, Ocepek-Welikson K (1993) Imipramine treatment of alcoholism with comorbid depression. Am J Psychiatry 150:963–965PubMedGoogle Scholar
  137. Nutt D, Adinoff B, Linnoila M (1989) Benzodiazepines in the treatment of alcoholism. In: Galanter M (ed) Treatment research. Recent Alcohol 7:283–313Google Scholar
  138. O’Malley S, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B (1992) Naltrexone and coping skills therapy for alcohol dependence: a controlled study. Arch Gen Psychiatry 49:881–887PubMedGoogle Scholar
  139. Oakley NR, Jones BJ, Tyers MB et al. (1988) The effect of GR38032F on alcohol consumption in the marmoset. Br J Pharmacol 95:870PGoogle Scholar
  140. Olivera AA, Sarvis S, Heard C (1990) Anxiety disorders coexisting with substance dependence: treatment with Buspirone. Curr Ther Res 47:52–61Google Scholar
  141. Overstreet DH, Rezvani AH, Janowsky DS (1992) Genetic animal models of depression and ethanol preference provide support for cholinergic and serotonergic involvement in depression and alcoholism. Biol Psychiatry 31:919–936PubMedGoogle Scholar
  142. Prather PL, Rezazadeh SM, Lai H (1991) Mianserin in the treatment of ethanol withdrawal in the rat: prevention of behaviours indicative of anxiety. Psycho-pharmacol Bull 27:285–289Google Scholar
  143. Privette TH, Hornsby RL, Myers RD (1988) Buspirone alters alcohol drinking induced in rats by tetrahydropapaveroline injected into brain monoaminergic pathways. Alcohol 5:147–152PubMedGoogle Scholar
  144. Quitkin FM, Rifkin A, Kaplan J et al. (1972) Phobic anxiety syndrome complicated by drug dependence and addiction. Arch Gen Psychiatry 27:159–162PubMedGoogle Scholar
  145. Regier DA, Farmer ME, Rae DS et al. (1990) Comorbidity of mental disorders with alcohol and other drug abuse. JAMA 264:2511–2518PubMedGoogle Scholar
  146. Reith MEA (1990) 5-HT3 receptor antagonists attenuate cocaine-induced locomotion in mice. Eur J Pharmacol 186:327–330PubMedGoogle Scholar
  147. Reyntjens A, Gelders IG, Hoppenbrowers ML, Vanden Bussche G (1986) Thymosthenic effects of ritanserin R55667, a centrally acting serotonin S-2 receptor blocker. Drug Dev Res 8:205–211Google Scholar
  148. Romach MK, Sellers EM (1991) Management of the alcohol withdrawal syndrome. Annu Rev Med 42:323–340PubMedGoogle Scholar
  149. Romach MK, Busto U, Somer G, Kaplan HL, Sellers EM (1992) Alcoholism, mental disorders and patient’s sex in benzodiazepine discontinuation. Annual Meeting of the American College of Neuropsychopharmacology San Juan/Puerto RicoGoogle Scholar
  150. Ross HE, Glaser FB, Germanson T (1988) The prevalence of psychiatric disorders in patients with alcohol and other drug problems. Arch Gen Psychiatry 45:1023–1031PubMedGoogle Scholar
  151. Rotham SW, Olney JW (1987) Excitotoxicity and the NMDA receptor. Trends Neurosci 10:299–302Google Scholar
  152. Rounsaville BJ, Dolinsky ZS, Babor TF et al. (1987) Psychopathology as a predictor of treatment outcome in alcoholics. Arch Gen Psychiatry 44:505–513PubMedGoogle Scholar
  153. Rowland NE, Morian KR (1992) Effect of dexfenfluramine on alcohol intake in alcohol-preferring “P” rats. Alcohol 9:559–561PubMedGoogle Scholar
  154. Samson HH (1987) Initiation of ethanol-maintained behaviour. A comparison of animal models and their implication to human drinking. In: Thompson T, Dews PB, Barrett JE (eds) Advances in behavioural pharmacology: neurobehavioural pharmacology, vol 6. Erlbaum, Hillsdale, pp 221–248Google Scholar
  155. Samson HH, Harris RA (1992) Neurobiology of alcohol abuse. Trends Pharmacol Sci 13:206–211PubMedGoogle Scholar
  156. Samson HH, Pfeffer AO, Tolliver GA (1988) Oral ethanol self-administration in rats: models of ethanol seeking behavior. Alcohol Clin Exp Res 12:591–598PubMedGoogle Scholar
  157. Samson HH, Doyle TF (1985) Oral ethanol self-administration in the rat: effect of naloxone. Pharmacol Biochem Behav 22:91–99PubMedGoogle Scholar
  158. Saunders JB (1989) The efficacy of treatment for drinking problems. Int Rev Psychiatry 1:121–138Google Scholar
  159. Seigel S (1989) Pharmacological conditioning and drug effects. In: Goudie AJ, Emmett-Oglesby MW (eds) Psychoactive drugs: tolerance and sensitization. Humana Clifton, pp 115–180Google Scholar
  160. Sellers EM, Zilm DH, Degani NC (1977) Comparative efficacy of proprancolol and chlordiazepoxide in alcohol withdrawal. J Stud Alcohol 38:2096–2108PubMedGoogle Scholar
  161. Sellers EM, Naranjo CA, Harrison M, Devenyi P, Roach C, Sykora K (1983) Diazepam loading: simplified treatment of alcohol withdrawal. Clin Pharmacol Ther 34:822–826PubMedGoogle Scholar
  162. Sellers EM, Romach MK, Frecker RC, Higgins GA (1991) Efficacy of the 5HT3 antagonist ondansetron in addictive disorders. Biol Psychiatry 2:894–897Google Scholar
  163. Sellers EM, Higgins GA, Sobell MB (1992) 5-HT and alcohol abuse. Trends Pharmacol Sci 13:69–75PubMedGoogle Scholar
  164. Signs SA, Schecter MD (1988) The role of dopamine and serotonin receptors in the mediation of the ethanol interoceptive cue. Pharmacol Biochem Behav 30: 55–64PubMedGoogle Scholar
  165. Sinclair JD (1974) Morphine suppresses alcohol drinking regardless of prior alcohol access duration. Pharmacol Biochem Behav 2:409–412PubMedGoogle Scholar
  166. Sinclair JD, Scheinin H, Lammintausta R (1992) Progressive suppression of aclohol drinking in the alcohol-preferring A A rat line with nalmefene. 22nd Annual Meeting of the Behaviour Genetics Association, BoulderGoogle Scholar
  167. Smail P, Stockwell T, Canter S et al. (1984) Alcohol dependence and phobic anxiety states. I: A prevalence study. Br J Psychiatry 144:53–57PubMedGoogle Scholar
  168. Sobell MB, Wilkinson DA, Sobell LC (1990) Alcohol and drug problems. In: Bellack AS, Hersen M, Kazdin AE (eds) International handbook of behaviour modification and therapy, 2nd edn. Plenum, New York, pp 415–435Google Scholar
  169. Soubrie P (1986) Reconciling the role of central serotonin neurons in human and animal behaviour. Behav Brain Sci 9:319–364Google Scholar
  170. Stefanini E, Frau M, Garau MG, Garau B, Fadda F, Gessa GL (1992) Alcohol-preferring rats have fewer dopamine D2 receptors in the limbic system. Alcohol 27:127–130Google Scholar
  171. Stolerman I (1992) Drugs of abuse: behavioural principles, methods and terms. Trends Pharmacol Sci 13:170–176PubMedGoogle Scholar
  172. Szabo G, Tabakoff B, Hoffman PL (1988) Receptors with V1 characteristics mediate the maintenance of ethanol tolerance by vasopressin. J Pharmacol Exp Ther 247:536–541PubMedGoogle Scholar
  173. Ticku MK, Kulkarniz K (1988) Molecular interactions of ethanol with GABAergic system and potential of RO-15–4513 as an ethanol antagonist. Pharmacol Biochem Behav 30:501–510PubMedGoogle Scholar
  174. Tollefson GD, Montague-Clouse J, Tollefson SL (1992) Treatment of comorbid generalized anxiety in a recently detoxified alcoholic population with a selective serotonergic drug (buspirone). J Clin Psychopharmacol 12:19–26PubMedGoogle Scholar
  175. Tomkins DM, Sellers EM (1992) Effect of ondansetron on ethanol intake and behaviour. Alcohol Clin Exp Res 16:368Google Scholar
  176. Tomkins DM, Higgins GA, Sellers EM (1993) Enhancement of ethanol intake in Wistar rats following pretreatment with low doses of 8-OH DPAT and gepirone using a limited access paradigm. British Pharmacological Society, winter meeting, C101Google Scholar
  177. Van der Hoek GA, Cooper SJ (1990) Evidence that ondansetron, a selective 5-HT3 antagonist, reduces concaine’s psychomotor stimulant effects in the rat. Psychopharmacology (Berl) 101:S59Google Scholar
  178. Volpicelli JR, Davis MG, Olgin JE (1986) Naltrexone blocks the post-shock increase of ethanol consumption. Life Sci 38:841–847PubMedGoogle Scholar
  179. Volpicelli JR, O’Brien CP, Alterman AI, Hayashida M (1990) Naltrexone and the treatment of alcohol dependence: initial observations. In: Reid LD (ed) Opioids, bulimia and alcohol abuse and alcoholism. Springer, Berlin Heibelberg New York, pp 195–214Google Scholar
  180. Volpicelli JR, Alterman AL, Hayashida M, O’Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49:876–880PubMedGoogle Scholar
  181. Walker DW, Zornetzer SF (1974) Alcohol withdrawal in mice: electroencephalographic and behavioural correlates. Electroencephalogr Clin Neurophysiol 36: 233–243PubMedGoogle Scholar
  182. Waller MB, McBride WJ, Lumeng L, Li T-K (1982) Induction of dependence on ethanol by free-choice drinking in alcohol-preferring rats. Pharmacol Biochem Behav 16:501–507PubMedGoogle Scholar
  183. Weiss F, Bloom FE, Koob GF (1992) Effects of ethanol self-administration on accumbens dopamine release: strain differences between alcohol-preferring (P) and genetically heterogeneous Wistar rats. Alcohol Clin Exp Res 16:367Google Scholar
  184. Whitton P, Curzon G (1990) Anxiogenic-like effects of infusing l-(3 chlorophenyl) piperazine (mCPP) into the hippocampus. Psychopharmacology (Berl) 100: 138–140Google Scholar
  185. Wilson GT (1988) Alcohol and anxiety. Behav Res Ther 26:369–381PubMedGoogle Scholar
  186. Wolffgramm J, Heyne A (1991) Social behaviour, dominance and social deprivation of rats determine drug choice. Pharmacol Biochem Behav 38:389–399PubMedGoogle Scholar
  187. Wong DT, Threlkeid PG, Lumeng L, Li T-K (1990) Higher density of serotonin 1A receptors in the hippocampus and cerebral cortex of alcohol preferring P rats. Life Sci 46:231–235PubMedGoogle Scholar
  188. Wright C, Moore RD (1989) Disulfiram treatment of alcoholism. Ann Intern Med 111:943–945Google Scholar

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© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • M. K. Romach
  • D. M. Tomkins

There are no affiliations available

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