Effects of Chronic Alcohol Consumption on Neurotransmitters, Part 2

by National Institute of Health

(Page 4 of 6)

Recent studies have suggested a link between stress and altered activity of the mesolimbic dopamine system. Stressful situations result in the increased release of hormones called glucocorticoids, most prominently cortisol. Studies have found that glucocorticoids can increase mesolimbic dopamine release. It has been suggested that the stress-induced increase in dopamine release may make the person more sensitive to the rewarding effects of AODs, which may represent one of the pathways leading to abuse of those drugs. Recently, researchers have utilized PET to study the relationship between cortisol release and amphetamine-induced dopamine release. These preliminary studies, which suggest a high correlation between cortisol release and dopamine release, may open the way for future studies of these relationships in alcoholics and their relatives. Other studies have found that actively drinking alcoholics appear to have an abnormal hormonal response to stress, which also may be present in the offspring of alcoholics who are not yet heavy drinkers.

Serotonin. Serotonin, another excitatory neurotransmitter involved in the brain's reward system, appears to play an important role in alcohol abuse. As with dopamine, animal studies have demonstrated that acute alcohol administration resulted in enhanced serotonin release, and withdrawal from alcohol was associated with reduced serotonin release. Moreover, studies have found that alcoholics with years of excessive alcohol consumption appeared to exhibit impaired serotonin and dopamine activity. (The reduction in serotonin in the brain is hypothesized to lead to the reduction in dopamine.) Finally, studies using SPECT found a genetic defect in the gene encoding a serotonin transporter in some people who were particularly sensitive to the toxic effects of chronic excessive alcohol consumption on the brain. The serotonin transporter is a protein located in serotonin-producing neurons that removes serotonin from the space between neurons to stop serotonin's effect on the signal-receiving neuron. Thus, people with abnormal serotonin transporter function may be particularly susceptible to the reduced excitatory effect of serotonin caused by heavy alcohol consumption. The reduced effect of serotonin, in turn, probably leads to reduced effects of dopamine. Thus, alcoholics with abnormal serotonin transporter function are likely to need greater amounts of alcohol to attain the pleasurable feelings associated with alcohol consumption.

One goal of research on serotonin and other neurotransmitters in alcoholism is to identify distinct biological subtypes of alcoholism and biological markers for them, which may then help to develop more targeted treatment approaches. For example, if one biological subtype of alcoholism was characterized by defective serotonin transporter function, brain scans for the presence of the serotonin transporter could serve as a tool to obtain a biological marker for this alcoholism subtype. Similarly, repeated scans after the administration of a potential treatment for the serotonin transporter deficiency could help identify the effect of that treatment. Future studies of the effects of chronic alcohol consumption on the serotonin system may clarify the role of serotonin and dopamine in alcoholism subtypes. Neuroimaging techniques may help to identify the specific chemicals, such as dopamine and serotonin, that are deficient in particular biological subtypes of alcoholism, and to monitor the effects of potential therapies targeted for the specific deficiency of the biological subtype.

Other Neurotransmitters. In addition to glutamate, dopamine, and serotonin, alcohol also acts on various other excitatory neurotransmitters conveying signals within the brain as well as to other organs, as follows (also see the table, above): acute administration of alcohol increases the excitatory effects of the neurotransmitter norepinephrine. Acetylcholine is an excitatory neurotransmitter that among other functions plays a role in memory. Chronic consumption of alcohol reduces the number of neurons containing acetylcholine. This reduction may be associated with the memory deficits commonly associated with heavy chronic alcohol consumption. Bombesin and cholecystokinin are compounds produced in the brain that stimulate the functioning of the intestines. Alcohol does not appear to influence the actions of these compounds, but both bombesin and cholecystokinin reduce the intake of alcohol.

Alcohol's Effects on Endogenous Opioids

Endogenous opioids are molecules produced in the body that resemble opium; they apparently act like excitatory neurotransmitters to stimulate neurons. It is hypothesized that endogenous opioids reinforce the effects of alcohol and play a role in the pleasurable effects of both acute and chronic alcohol consumption, but their specific part in alcohol abuse and dependence remains to be clarified. What is known is that alcohol influences one of the opioid receptors - the mu receptor - in the brain. For example, chronic heavy drinkers have alterations of mu receptors in neurons both in the outer layer of the brain and in structures deep in the center of the brain. In addition, studies have found that a medication called naltrexone that inhibits opiate receptors in the brain is an effective treatment for alcoholism, particularly for people with a family history of alcoholism or with a strong craving for alcohol. Other studies have found that alcoholics carrying a specific variant of the mu receptor have a lower relapse rate after treatment with naltrexone than do those carrying other receptor variants. These findings suggest that alcoholics with a particular genetic makeup are particularly likely to benefit from treatment with naltrexone. Because PET technology offers promise as a tool for determining the density and the distribution of mu opiate receptors in the brain, this technique may help identify alcoholics who could benefit from interventions such as naltrexone, which affect these receptors. Thus, PET studies to identify mu opiate receptors in the brain may be a tool for identifying a distinct biological subtype of alcoholism; and PET findings could serve as a biological marker of mu opiate receptor dysfunction in the brain.

About the Author

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