Alcoholism and the Brain : Brain Damage

by National Institute of Health

(Page 3 of 5)

The major excitatory neurotransmitter in the human brain is the amino acid glutamate. Small amounts of alcohol have been shown to interfere with glutamate action. This interference could affect several brain functions, including memory, and it may account for the short-lived condition referred to as "alcoholic blackout." Chronic alcohol consumption increases glutamate receptor sites in the hippocampus, an area in the limbic system that is crucial to memory and often involved in epileptic seizures. During alcohol withdrawal, glutamate receptors that have adapted to the long-term presence of alcohol may become overactive, and this overactivity has been repeatedly linked to neuronal death, which is manifested by conditions such as stroke and seizures. Deficiencies of thiamine caused by malnutrition may contribute to this potentially destructive overactivity.

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter. Available evidence suggests that alcohol3 initially potentiates GABA's effects (it increases inhibition, and often the brain becomes mildly sedated). (The amount of alcohol needed to cause this effect depends on the person.) However, over time, prolonged, excessive alcohol consumption reduces the number of GABA receptors. When the person stops drinking, decreased inhibition combined with a deficiency of GABA receptors may contribute to overexcitation throughout the brain. This in turn can contribute to withdrawal seizures within a day or two. It should be noted that the balance between the inhibitory action of GABA and the excitatory action of glutamate is a major determinant of the level of activity in certain regions of the brain; the effects of GABA and glutamate on withdrawal and brain function are probably interactive.

Alcohol directly stimulates release of the neurotransmitter serotonin, which is important in emotional expression, and of the endorphins, natural substances related to opioids, which may contribute to the "high" of intoxication and the craving to drink. Alcohol also leads to increases in the release of dopamine (DA), a neurotransmitter that plays a role in motivation and in the rewarding effects of alcohol. Changes in other neurotransmitters such as acetylcholine have been less consistently defined. Future research should help to clarify the importance of many neurochemical effects of alcohol consumption. Furthermore, areas amenable to pharmacological treatment could be identified by studying regionally specific brain neurochemistry in vivo using neuroimaging methods such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT). New information from neuroimaging studies could link cellular changes directly to brain consequences observed clinically. In the absence of a cure for alcoholism, a detailed understanding of the actions of alcohol on nerve cells may help in designing effective therapies.

Techniques for Studying Alcohol-Related Brain Damage

Researchers use multiple methods to understand the etiologies and mechanisms of brain damage across subgroups of alcoholics. Behavioral neuroscience offers excellent techniques for sensitively assessing distinct cognitive and emotional functions - for example, the measures of brain laterality and frontal system integrity mentioned earlier. Followup post mortem examinations of brains of well-studied alcoholic patients offer clues about the locus and extent of pathology and about neurotransmitter abnormalities. Neuroimaging techniques provide a window on the active brain and a glimpse at regions with structural damage.

Behavioral Neuroscience

Behavioral neuroscience studies the relationship between the brain and its functions - for example, how the brain controls executive functions and spatial cognition in healthy people, and how diseases like alcoholism can alter the normal course of events. This is accomplished by using specialized tests designed expressly to measure the functions of interest. Among the tests used by scientists to determine the effects of alcoholism on executive functions controlled by the frontal lobes are those that measure problem-solving abilities, reasoning, and the ability to inhibit responses that are irrelevant or inappropriate. Tests to measure spatial cognition controlled by the right hemisphere include those that measure skills important for recognizing faces, as well as those that rely on skills required for reading maps and negotiating two- and three-dimensional space (visuospatial tasks) . With the advent of sophisticated neuroimaging techniques, scientists can even observe the brain while people perform many tasks sensitive to the workings of certain areas of the brain.

Neuropathology

Researchers have gained important insights into the anatomical effects of long-term alcohol use from studying the brains of deceased alcoholic patients. These studies have documented alcoholism-related atrophy throughout the brain and particularly in the frontal lobes. Post mortem studies will continue to help researchers understand the basic mechanisms of alcohol-induced brain damage and regionally specific effects of alcohol at the cellular level.

Neuroimaging

Remarkable developments in neuroimaging techniques have made it possible to study anatomical, functional, and biochemical changes in the brain that are caused by chronic alcohol use. Because of their precision and versatility, these techniques are invaluable for studying the extent and the dynamics of brain damage induced by heavy drinking. Because a patient's brain can be scanned on repeated occasions, clinicians and researchers are able to track a person's improvement with abstinence and deterioration with continued abuse. Furthermore, brain changes can be correlated with neuropsychological and behavioral measures taken at the same time. Brain imaging can aid in identifying factors unique to the individual which affect that person's susceptibility to the effects of heavy drinking and risk for developing dependence, as well as factors that contribute to treatment efficacy.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.