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Anxiety and Alcoholism: A Serotonin Link

  • Gary D. Tollefson (a1)


The augmentation of serotonin (5-HT) neurotransmission attenuates alcohol consumption, whereas depletion enhances use. A number of serotonin-specific pharmacological probes appear to be effective in reducing the voluntary consumption of alcohol. The 5-HT1A receptor agonist buspirone is an anxiolytic which has been shown to diminish the desire to consume alcohol in anxious alcoholic patients. Thus, serotonin may represent a common denominator for a spectrum of behavioural disorders including anxiety and alcoholism. Novel serotonin drugs, such as the azapirones, may usefully supplement conventional treatment strategies for substance abuse.



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Amies, P. L., Gelder, M. G. & Shaw, P. M. (1983) Social phobia: a comparative clinical study. British Journal of Psychiatry, 142, 174179.
Ballenger, J., Goodwin, F., Major, L., et al (1979) Alcohol and central serotonin metabolism in man. Archives of General Psychiatry, 36, 224227.
Banki, C. M. (1978) 5-Hydroxytryptamine content of the whole blood in psychiatric illness and alcoholism. Acta Psychiatrica Scandinavica, 57, 232.
Banki, C. M. (1981) Factors influencing monoamine metabolites and tryptophan in patients with alcohol dependence. Journal of Neural Transmission, 50, 98101.
Barnes, G. (1979) The alcoholic personality: a reanalysis of the literature. Journal of the Studies on Alcohol, 40, 571634.
Bibb, J. & Chambless, D. L. (1986) Alcohol use and abuse among diagnosed agoraphobics. Behaviour Research and Therapy, 24, 4958.
Blier, P. & deMontigny, C. (1987) Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiologic studies in the rat brain. Synapse, 1, 470480.
Boismare, F., Lhuintre, J. P., Daoust, M., et al (1987) Platelet affinity for serotonin is increased in alcoholics and former alcoholics: a biological marker for dependence? Alcohol and Alcoholism, 22, 155159.
Bruno, F. (1989) Buspirone in the treatment of alcoholic patients. Psychopharmacology, 22 (suppl. ), 4959.
Collins, A. C. (1979) Genetics of ethanol preferences: role of neurotransmitters. In Biochemistry and Pharmacology of Ethanol, vol. 2 (eds Majchrowicz, E. & Noble, E. P.), p. 207. New York: Plenum Press.
Conger, J.J. (1956) Alcoholism: theory, problem and challenge, II: reinforcement theory and the dynamics of alcoholism. Quarterly Journal of Studies on Alcohol, 13, 296305.
Curlee, J. & Stern, H. (1973) The fear of heights among alcoholics. Bulletin of the Menninger Clinic, 37, 615623.
Daoust, M., Chretien, P., Moore, N., et al (1985) Isolation and striatal (3H) serotonin uptake: role in the voluntary intake of ethanol by rats. Pharmacology, Biochemistry and Behavior, 2, 205208.
Department of Health and Human Services (1987) Sixth Special Report to the U.S. Congress on Alcohol and Health, p. 21. Rockville, MA: US Government Printing Office.
Friedman, M. J., Krstulovic, A. M., Severinghaus, J. M., et al (1988) Altered conversion of tryptophan in kynurenine in newly abstinent alcoholics. Biological Psychiatry, 23, 8993.
Gardner, C. R. (1986) Recent development in 5HT-related pharmacology of animal models of anxiety. Pharmacology, Biochemistry and Behavior, 24, 14791485.
Gatto, G. J., McBride, W. J., Murphy, J. M., et al (1989) Effects of serotonin (5-HT) agonists on alcohol drinking behavior of the NP (alcohol nonpreferring) line of rats (abstract). Alcoholism, 13, 305.
Gill, K., Filion, Y. & Amit, Z. (1988) A further examination of the effects of sertraline on voluntary ethanol consumption. Alcohol, 5, 355358.
Gorelick, D. A. (1986) Effect of fluoxetine on alcohol consumption (abstract). Alcohol, 10, 113.
Gray, J. A. (1982) The Neuropsychology of Anxiety: An Inquiry into the Functions of the Septo-Hippocampal System. New York: Oxford University Press.
Haraguchi, M., Samson, H. H. & Tolliver, G. A. (1989) Reduction in oral ethanol self-administration in the rat by the 5-HT uptake blocker fluoxetine (abstract). Alcoholism, 13, 305.
Hill, S. Y. (1974) Intraventricular injection of 5-hydroxytryptamine and alcohol consumption in rats. Biological Psychiatry, 8, 151158.
Hippocrates (1886) Aphorisms VII, 56. In Works of Hippocrates, Vol. 2, p. 269. New York: William Wood.
Holman, R. B. & Snape, B. M. (1985) Effects of ethanol on 5-hydroxytryptamine release from rat corpus striatum in vivo. Alcohol, 2, 249253.
Jellinek, E. M. (1954) The problems of alcohol. In Alcohol, Science, and Society (ed. Yale University Center of Alcohol Studies Staff). Westport, CT: Greenwood Press.
Kahn, R. S., Westenberg, H. G. M., Verhoeven, W. M. A., et al (1987) Effect of a serotonin precursor uptake inhibitor in anxiety disorders; a double-blind comparison of 5-hydroxytryptophan, clomipramine and placebo. International Clinical Psychopharmacology, 2, 3345.
Kahn, R. S., van Praag, H. M., Wetzler, S., et al (1988) Serotonin and anxiety revisited. Biological Psychiatry, 23, 189203.
Karno, M., Golding, J. M., Sorenson, S. B., et al (1988) The epidemiology of obsessive–compulsive disorders in five U.S. communities. Archives of General Psychiatry, 45, 10941099.
Kempf, E., Fuhrmann, G. & Ebel, A. (1985) Genotypic variations in ethanol effect of striatal and hippocampal transmitter interactions. Alcohol, 2, 231237.
Kent, T. A., Campbell, J. L., Pazdernik, T. L., et al (1985) Blood platelet uptake of serotonin in men alcoholics. Journal of the Studies on Alcohol, 46, 357359.
Kushner, M. G., Sher, K. J. & Beitman, B. D. (1990) The relation between alcohol problems and the anxiety disorders. American Journal of Psychiatry, 147, 685695.
Lawrin, M. O., Naranjo, C. A. & Sellers, E. M. (1983) Studies on the mechanism of zimelidine-induced decrease in alcohol consumption in rats. Proceedings of the Canadian Federation of Biological Societies, 26, 116.
LeBourhis, B., Uzan, A., Aufrere, G., et al (1981) Effects of indalpine, a specific 5-HT reuptake inhibitor, on the ethanol behavioral dependence and on the voluntary ethanol consumption in rats. Annates Pharmaceutiques Francoises, 29, 1120.
Levy, A. D., McBride, W. J. & Murphy, J. M. (1989) Effects of intra-accumbens infusions of DA & 5-HT on ethanol intake of alcohol-preferring (P) rats (abstract). Alcoholism, 13, 305.
Leysen, J. E., Gommeren, W. & van Gompel, P. (1985) Receptor binding properties in vitro and in vivo of ritanserin: a very potent and long acting 5HT2 antagonist. Molecular Psychopharmacology, 27, 600611.
Linnoila, M., Eckardt, M., Durcan, M., et al (1987) Interactions of serotonin with ethanol: clinical and animal studies. Psychopharmacology Bulletin, 23, 452457.
McBride, W. J., Lumeng, L. & Li, T. K. (1988) Effects of serotonin and dopamine agents on ethanol intake of alcohol-preferring (P) rats (abstract). Alcoholism, 12, 306.
Marks, I. M. (1987) Fears, Phobias, and Rituals. New York: Oxford University Press.
Modell, J. G., Mountz, J. M. & Beresford, T. P. (1990) Basal ganglia/limbic striatal and thalamocorticol involvement in craving and loss of control in alcoholism. Journal of Neuropsychiatry and Clinical Neurosciences, 2, 123144.
Morey, L. C. & Blashfield, R. K. (1981) Empirical classifications of alcoholism: a review. Journal of the Studies on Alcohol, 42, 925937.
Morinan, A. (1987) Reduction in striatal 5-hydroxytryptamine turnover following chronic administration of ethanol to rats. Alcohol, 22, 5360.
Murphy, J. M., McBride, W. J., Lumeng, L., et al (1982) Regional brain levels of monoamines in alcohol-preferring and nonpreferring lines of rats. Pharmacology, Biochemistry and Behavior, 16, 145149.
Murphy, J. M., Waller, M. B., Gatto, G. J., et al (1985) Monoamine uptake inhibitors attenuate ethanol intake in alcohol-preferring (P) rats. Alcohol, 2, 349352.
Murphy, J. M., McBride, W. J., Lumeng, L., et al (1989) Effects of spiroxatrine on the fluoxetine-induced reduction of ethanol intake of alcohol preferring rats. Alcoholism: Clinical and Experimental Research, 13, 305.
Murphy, J. M. & Pigott, T. A. (1990) A comparative examination of a role for serotonin in obsessive–compulsive disorder, panic, and anxiety. Journal of Clinical Psychiatry, 51 (suppl. ), 5358.
Naranjo, C. A., Sellers, E. M. & Larwin, M. O. (1986) Modulation of ETOH intake by 5-HT uptake inhibitor. Journal of Neuropsychiatry and Clinical Neurosciences, 47 (suppl. ), 1622.
Neiman, J., Beving, H. & Malmgren, R. (1987) Platelet uptake of serotonin (5-HT) during ethanol withdrawal in male alcoholics. Thrombosis Research, 46, 803809.
Noyes, R. Jr, Crowe, R. R., Harris, E. L., et al (1986) Relationship between panic disorder and agoraphobia: a family study. Archives of General Psychiatry, 43, 227232.
Olivera, A. A., Sarvis, S. & Heard, C. (1990) Anxiety disorders coexisting with substance dependence: treatment with buspirone. Current Therapeutic Research, 47, 5260.
Pazos, A. & Palacios, J. M. (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Research, 346, 205230.
Peroutka, S., Sleight, A. J., McCarthy, B. G., et al (1989) The clinical utility of pharmacological agents that act as serotonin receptors. Journal of Neuropsychiatry and Clinical Neurosciences, 1, 253262.
Powell, B. J., Penick, E. C., Othmer, E., et al (1982) Prevalence of additional psychiatric syndromes among male alcoholics. Journal of Clinical Psychiatry, 43, 404407.
Privette, T. H., Hornsby, R. L. & Myers, R. D. (1987) Buspirone alters alcohol drinking induced in rats by tetrahydropapaveroline injected into brain monoaminergic pathways. Alcohol, 5, 147152.
Quitkin, F. M., Rifkin, A., Kaplan, J., et al (1972) Phobic anxiety syndrome complicated by drug dependence and addiction: a treatable form of drug abuse. Archives of General Psychiatry, 27, 154162.
Richardson, J. S. & Novakowski, D. M. (1978) Brain monoamines and free choice ethanol consumption in rats. Drug and Alcohol Dependence, 3, 253264.
Robins, L. N., Helzer, J. E., Weissman, M. M., et al (1984) Lifetime prevalence of specific psychiatric disorders in three sites. Archives of General Psychiatry, 41, 949958.
Rockman, G. E., Amit, Z., Carr, G., et al (1979) Attenuation of ethanol intake by 5-hydroxytryptamine uptake blockade in laboratory rats. I. Involvements of brain 5-hydroxytryptamine in the mediation of the positive reinforcing properties of ethanol. Archives Internationales de Pharmacodynamic et de Therapy, 241, 245259.
Rockman, G. E., Amit, Z., Brown, Z. W., et al (1982) An investigation of the mechanisms of action of 5-hydroxytryptamine in the suppression of ethanol intake. Neuropharmacology, 21, 341347.
Rosenthal, N. E., Davenport, Y., Cowdry, R. W., et al (1980) Monoamine metabolites in cerebrospinal fluid of depressive subgroups. Psychiatry Research, 2, 113119.
Ross, H. E., Glasser, F. B. & Germanson, T. (1988) The prevalence of psychiatric disorders in patients with alcohol and other drug problems. Archives of General Psychiatry, 45, 10231031.
Roy, A., Virkkunen, M. & Linnoila, M. (1987) Reduced central serotonin turnover in a subgroup of alcoholics. Progress in Neuro-psychopharmacology and Biologic Psychiatry, 11, 173177.
Sellers, E. M. & Naranjo, C. A. (1986) Therapeutic use of serotonergic drugs in alcohol abuse. Clinical Neuropharmacology, 9, 6062.
Sher, K. J. (1986) Stress response dampening. Excerpt from Alcohol and tension reduction: an update on research and theory (H. Cappell & J. Greeley). In Psychological Theories of Drinking and Alcoholism in Psychological Theories of Drinking and Alcoholism (eds Blane, H. T. & Leonard, K. E.). New York: Guilford Press.
Sjoquist, B., Liljequist, S. & Engel, J. V. (1982) Increased salsolinol levels in rat striatum and limbic forebrain following chronic ethanol treatment. Journal of Neurochemistry, 39, 259262.
Smail, P., Stockwell, T., Canter, S., et al (1984) Alcohol dependence and phobic anxiety states, I. A prevalence study. British Journal of Psychiatry, 144, 5357.
Solomon, J. (1982) Alcoholism and clinical psychiatry. In Alcoholism and Clinical Psychiatry (ed. Solomon, J.). New York: Plenum Press.
Sun, G. Y. & Sun, A. Y. (1985) Ethanol and membrane lipids. Alcohol, 9, 164180.
Takahashi, S., Yamane, H., Kondo, H., et al (1974) CSF monoamine metabolites in alcoholism, a comparative study with depression. Folia Psychiatrica et Neurologica Japanica, 28, 347354.
Thoren, P., Asberg, M., Cronholm, B., et al (1980) Clomipramine treatment of obsessive compulsive disorder: I. A controlled clinical trial. Archives of General Psychiatry, 37, 12811289.
Thyer, B. A., Parrish, R. T., Himle, J., et al (1986) Alcohol abuse among clinically anxious patients. Behaviour Research and Therapy, 24, 357359.
Tollefson, G. D., Montague-Clouse, J. & Lancaster, S. P. (1990) Buspirone in comorbid alcohol dependency and generalized anxiety disorders. Drug Therapy, 20(suppl. ), 3550.
Tytell, M. & Myers, R. D. (1973) Metabolism of (14C)-serotonin in the coudate nucleus, hypothalamus and reticular formation of the rat after ethanol administration. Biochemical Pharmacology, 2, 361372.
van Praag, H. M., Lemus, C. Z. & Kahn, R. S. (1987) Hormonal probes of central serotonergic activity: do they really work? Biological Psychiatry, 22, 8698.
Weiss, K. J. & Rosenberg, D. J. (1985) Prevalence of anxiety disorder among alcoholics. Journal of Clinical Psychiatry, 46, 34.
Weissman, M. M., Myers, J. K. & Harding, P. S. (1980) Prevalence and psychiatric heterogeneity of alcoholism in United States urban community. Journal of the Studies on Alcohol, 41, 672681.
Zabik, J. K., Binkerd, K. & Roache, J. D. (1985) Serotonin and ethanol aversion in the rat. In Research Advances in New Psychopharmacologic Treatment for Alcoholism (eds Naranjo, C. A. & Sellers, E. M.), pp. 7593. Amsterdam: Elsevier.
Zohar, J., Zohar-Kadouch, R. C., Insel, T. R., et al (1988) Serotonergic responsivity in obsessive–compulsive disorder: effects of chronic clomipramine treatment. Archives of General Psychiatry, 45, 167172.


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Anxiety and Alcoholism: A Serotonin Link

  • Gary D. Tollefson (a1)
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