Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-18T19:39:39.569Z Has data issue: false hasContentIssue false
  • English
  • Français

Alcohol and the brain

Pharmacological insights for psychiatrists

Published online by Cambridge University Press:  03 January 2018

David Nutt
David Nutt*
Affiliation:
Division of Psychiatry, Psychopharmacology Unit, School of Medical Sciences, University Walk, Bristol BS8 ITD. Tel: 0117 925 3066: Fax: 0117 927 7057: e-mail: david.j.nutt@bristol.ac.uk
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Alcohol misuse, as well as being a major form of psychiatric morbidity, is also commonly associated with other psychiatric disorders. A greater understanding of the brain mechanisms underlying the adverse effects of alcohol is now possible, thanks to significant research advances made over the past decade.

Aims

To elucidate for psychiatrists the growing knowledge of the importance of specific neurotransmitter interactions in the effects of alcohol.

Method

A survey of the literature, extracting current knowledge of interest to psychiatrists.

Results

There is good evidence that the acute effects of alcohol are mediated through interactions with amino acid neurotransmitters plus parallel changes in amines such as noradrenaline, dopamine and serotonin. Neuroadaptive responses at amino acid receptors probably underlie significant components of the withdrawal syndrome and probably also contribute to neuronal death found in chronic alcoholism.

Conclusions

An understanding of the pharmacology of alcohol use may lead to greater ability to treat psychiatric consequences of alcoholism, and may also prevent some of the secondary psychiatric comorbidity and later brain damage.

Type
Review Article
Information
The British Journal of Psychiatry , Volume 175 , Issue 2 , August 1999 , pp. 114 - 119
Copyright
Copyright © 1999 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abi-Dargham, A., Krystal, J. H., Anjilvel, S., et al (1998) Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [123I]iomazenil. American Journal of Psychiatry, 155, 1550–1555.CrossRefGoogle ScholarPubMed
Bailey, J. E., Potokar, J., Caupland, N. J., et al (1995) The 5-HT3 antagonist ondansetron reduces gastrointestinal side effects induced by a specific serotonin re-uptake inhibitor in man. Journal of Psychopharmacology, 9, 137–141.Google Scholar
Cloninger, C. R. (1987) Neurogenetic adaptive mechanisms in alcoholism. Science, 236, 410–416.CrossRefGoogle ScholarPubMed
Collingridge, G. L. & Bliss, T. V. P. (1995) Memories of NMDA receptors and LTP. Trends in Neuroscience, 18, 54–56.CrossRefGoogle ScholarPubMed
Cowley, D. S., Roy-Byrne, P. P., Godon, C., et al (1992) Response to diazepam in sons of alcoholics. Alcoholicism: Clinical and Experimental Research, 16, 1057–1063.CrossRefGoogle ScholarPubMed
George, D. T., Benkelfat, C., Rawlings, R. R., et al (1997) Behavioral and neuroendocrine responses to m-chlorophenylpiperazine in subtypes of alcoholics and in healthy comparison subjects. American Journal of Psychiatry, 154, 81–87.Google ScholarPubMed
Gilman, S., Koeppe, R. A., Adams, K., et al (1996) Positron emission tomographic studies of cerebral benzodiazepine-receptor binding in chronic alcoholics. Annals of Neurology, 40, 163–171.CrossRefGoogle ScholarPubMed
Glue, P. W. & Nutt, D. (1990) Overexcitement and disinhibition. Dynamic neurotransmitter interactions in alcohol withdrawal. British Journal of Psychiatry, 157, 491–499.Google Scholar
Heinz, A., Ragan, P., Jones, D. W., et al (1998) Reduced central serotonin transporters in alcoholism. American Journal of Psychiatry, 155, 1544–1549.CrossRefGoogle ScholarPubMed
Higley, J. D. Soumi, S. J. & Linnoila, M. (1996) A nonhuman primate model of Type II excessive alcohol consumption? Part I. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and diminished social competence correlate with excessive alcohol consumption. Alcoholism: Clinical and Experimental Research, 20, 629–642.CrossRefGoogle ScholarPubMed
Jackson, H. C. & Nutt, D. J. (1995) Inverse agonists and alcohol. In Inverse Agonists (eds M. Sarter, D. J. Nutt & R. Lister), pp. 113–138. New York: John Wiley & Sons.Google Scholar
Johnson, B. A., Campling, G. M., Griffiths, P., et al (1993) Attenuation of some alcohol-induced mood changes and the desire to drink by 5-HT3 receptor blockage: a preliminary study in healthy male volunteers, Psychopharmacology, 112, 142–144.CrossRefGoogle Scholar
Kranzler, H. R., Burleson, J. A., Del Boca, F. K., et al (1994) Buspirone treatment of anxious alcoholics. Archives of General Psychiatry, 51, 720–731.Google Scholar
Lamparski, D. M., Roy, A., Nutt, D. J., et al (1991) The criteria of Cloninger et al. and von Knorring et al. for subgrouping alcoholics: a comparison in a clinical population. Acta Psychiatrica Scandinavica, 84, 497–502.Google Scholar
Lingford-Hughes, A. R., Action, P. D., Gacinovic, S., et al (1998) Reduced levels of GABA–benzodiazepine receptor in alcohol dependency in the absence of grey matter atrophy. British Journal of Psychiatry, 173, 116–122.CrossRefGoogle ScholarPubMed
Little, H. J. (1991) The role of neuronal calcium channels in dependence on ethanol and other sedatives/hypnotics. Pharmacological Therapy, 50, 347–365.CrossRefGoogle ScholarPubMed
Littleton, J. M. (1995) Acamprosate in alcohol dependence: how does it work? Addiction, 90, 1179–1188.Google Scholar
Lovinger, D. M., White, G. & Weight, F. F. (1989) Ethanol inhibits NMDA activated ion currents in hippocampal neurones. Science, 243, 1721–1724.CrossRefGoogle Scholar
Luddens, H., Pritchett, D. B., Kohier, M., et al (1990) Cerebellar GABA receptor selective for a behavioural alcohol antagonist. Nature, 346, 648–651.CrossRefGoogle ScholarPubMed
Luddens, , & Korpi, E. R. (1995) Biological function of GABA-A/benzodiazepine receptor heterogeneity. Journal of Psychiatry Research, 29, 77–94.Google Scholar
Mhatre, M., Mehta, A. K. & Ticku, M. K. (1988) Chronic ethanol administration increases the binding of the benzodiazepine inverse agonist and alcohol antagonist (3H) Ro 15-4513 in rat brain. European Journal of Pharmacology, 153, 141–145.CrossRefGoogle ScholarPubMed
Nutt, D. (1993) Neurochemistry and neuropharmacology. In Seminars in Basic Neurosciences (eds Morgan, G. & Butler, S.), pp. 71–111. London: Royal College of Psychiatrists.Google Scholar
Nutt, D. (1996) Addiction: brain mechanisms and their treatment implications. Lancet, 347, 31–36.CrossRefGoogle ScholarPubMed
Nutt, D., Adinoff, B. & Linnioila, M. (1988) Benzodiazepinesin the treatment of alcoholism. In Advances in Alcoholism VII (ed. Gallanter, M.), pp. 283–313. New York: Plenum.Google Scholar
Nutt, D., & Peters, T. J. (1994) Alcohol: the drug. British Medical Bulletin (special issue: Alcohol and Alcohol Problems), 50, 5–17.Google Scholar
O'Malley, S. S., Jaffe, A. J., Chang, G., et al (1993) Naltrexone and coping skills therapy for alcohol dependence: a controlled study. Archives of General Psychiatry, 49, 881–887.Google Scholar
Ritzmann, R. F. & Tabalcoff, B. (1976) Dissociation of alcohol tolerance and dependence. Nature, 243, 418–420.CrossRefGoogle Scholar
Sass, H., Soyka, M., Mann, K., et al (1996) Relapse prevention by acamprosate: results from a placebo-controlled study on alcohol dependence. Archives of General Psychiatry, 53, 673–680.Google Scholar
Sellers, E. M., Toneatto, T., Romach, M. K., et al (1994) Clinical efficacy of the 5-HT3 antagonist ondansetron in alcohol abuse and dependence. Alcoholism: Clinical and Experimental Research, 18, 879–885.Google Scholar
Shaw, G. K., Waller, S., Majumdar, S. K., et al (1994) Tiapride in the prevention of relapse in recently detoxified alcoholics. British Journal of Psychiatry, 165, 515–523.CrossRefGoogle ScholarPubMed
Signs, S. A. & Schechter, M. D. (1988) The role of dopamine and serotonin receptors in the mediation of the ethanol interoceptive cue. Pharmacology Biochemistry and Behaviour, 30, 55–64.Google Scholar
Ticku, M. K., Mhatre, M. & Mehta, A. K. (1992) Modulation of GABAergic transmission by ethanol. In Advances in Biochemical Psychopharmacology: GABAergic Synaptic Transmission – Molecular, Pharmacological and Clinical Aspects (eds Biggio, G., Concas, A. & Costa, E.), pp. 255–268. New York: Raven Press.Google Scholar
Ulm, R. R., Volpicelli, J. R. & Volpicelli, L. A. (1995) Opiates and alcohol self-administration in animals. Journal of Clinical Psychiatry, 56, 5–14.Google Scholar
Virkunnen, M., Rawlings, R., Tolcola, R., et al (1994) CSF biochemistries, glucose metabolism and diurnal activity rhythms in alcoholic, violent attenders, fire setters and healthy volunteers. Archives of General Psychiatry, 51, 20–27.CrossRefGoogle Scholar
Volkow, N. D., Wang, G.-J., Hitzemann, R., et al (1993) Decreased cerebral response to inhibitory neurotransmission in alcoholics. American Journal of Psychiatry, 150, 417–422.Google Scholar
Volkow, N. D., Wang, G.-J., Beglelter, H., et al (1995) Regional brain metabolic response to lorazepam in subjects at risk for alcoholism. Alcoholism: Clinical and Experimental Research, 19, 510–516.Google Scholar
Volpicelli, J. R., Alterman, A. I., Hayashida, M., et al (1993) Naltrexone in the treatment of alcohol dependence. Archives of General Psychiatry, 49, 876–880.Google Scholar
Volpicelli, J. R., Rhines, K. C., Rhines, J. S., et al (1997) Naltrexone and alcohol dependence: role of subject compliance. Archives of General Psychiatry, 54, 737–742.CrossRefGoogle ScholarPubMed
Von Knorring, A. L., Bohman, M., Von Knorring, L., et al (1985) Platelet MAO activity as a biological marker in subgroups of alcoholism. Acta Psychiatrica Scandinavica, 72, 51–58.CrossRefGoogle ScholarPubMed
Wafford, K. A., & Whiting, P. J. (1992) Ethanol potentiation of GABAA receptors requires phosphorylation of the alternatively spliced variant of the gamma-2 subunit. FEBS Letters, 313, 113–117.Google Scholar
Weight, F. F., Peoples, R. W., Wright, J. M., et al (1993) Ethanol action on excitatory amino acid activated ion channels. In Advances in Biomedical Alcoholism Research (eds Taberner, P. V. & Badawy, A. A.). Oxford: Pergamon Press.Google Scholar
Wolfe, S. M. & Victor, M. (1969) The relationship of hypomagnesaemia and alkalosis to alcohol withdrawal symptoms. Annals of the New York Academy of Sciences, 162, 973–984.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.