Effects of Chronic Alcohol Consumption on Neurotransmitters

by National Institute of Health

(Page 3 of 6)

Overview of Neuronal Communication

To understand how chronic excessive alcohol use associated with alcohol dependence affects brain function, it is important to understand how neurons communicate with each other through electrical and chemical signals. Nerve signals are transmitted from one region of the brain to another region of the brain or to the rest of the body through serial communication between two or more neurons located next to each other. When a neuron is activated, an electrical signal is generated (usually near the neuron's body), which travels along the membrane surrounding the cell body and the long extension protruding from it (the axon). When the signal reaches the end of the axon, it triggers the release of neurotransmitters from the cell. These neurotransmitters travel across the narrow space separating one neuron from another (the synaptic cleft). On the signal-receiving neuron, the neurotransmitter molecules then interact with receptors, and this interaction either promotes or prevents the generation of new electrical signals in that neuron, depending on the neurotransmitter. Neurotransmitters that promote the generation of a new nerve signal are called excitatory neurotransmitters; those that prevent the generation of a new nerve signal are called inhibitory neurotransmitters. Many neurotransmitters can have both excitatory and inhibitory effects, depending on which brain region is studied and which receptors are present on the signal-receiving neurons. Neurotransmitters that often have excitatory effects include dopamine, glutamate, and serotonin; neurotransmitters that primarily have inhibitory effects are GABA and glycine.

Alcohol's effects on the brain are mediated by numerous neurotransmitters and their highly complex interactions. In general, the pleasurable psychological experiences associated with alcohol consumption appear to be mediated by dopamine, noradrenaline, and the endogenous opioids and their receptors. Other neurotransmitters commonly affected by alcohol are glutamate and GABA.

Alcohol's Effects on Inhibitory Neurotransmitters

Alcohol is thought to influence two inhibitory neurotransmitters - GABA and glycine. Alcohol appears to enhance the inhibitory actions of GABA, which may contribute to both the acute and the chronic effects of alcohol and to the phenomena of alcohol dependence, tolerance, and withdrawal. Chronic alcohol consumption leads to a decline in the number of GABA receptors in the brain and reduces GABA's ability to bind to its receptors, thereby allowing the body to compensate for the alcohol-induced enhancement of GABA's actions. These effects are a part of the changes in brain function that lead to tolerance and dependence on alcoho. When alcohol is withheld, however, and its stimulating effect on GABA is eliminated, the body suddenly has too few GABA receptors to balance the actions of the excitatory neurotransmitters. As a result, the brain experiences an excess of excitatory nerve signals, a phenomenon known as rebound hyperexcitability. This hyperexcitability may contribute to the physical and psychological manifestations of alcohol withdrawal.

Alcohol's effects on the inhibitory neurotransmitter glycine are controversial, however. Studies have found that both acute and chronic alcohol consumption exerted only minimal effects on the role of glycine in the nervous system.

Alcohol's Effects on Excitatory Neurotransmitters

Alcohol consumption appears to influence the transmission of signals mediated by many excitatory neurotransmitters, most prominently glutamate, dopamine, and serotonin.

Glutamate. Glutamate exerts its effects by interacting with several types of receptors, including one called the N-methyl-D-aspartate receptor. Alcohol acts on these NMDA receptors, inhibiting their functions and thereby diminishing glutamate-mediated neurotransmission. NMDA receptors may play a role in memory formation; prenatal, acute, or chronic alcohol exposure may hinder the person's ability to learn and to retain new information.

Dopamine. In contrast to its dampening effects on the activity of the glutamate system, acute alcohol ingestion enhances the excitatory effect of dopamine. Correspondingly, acute withdrawal from alcohol reduces dopamine's excitatory effect. PET studies have confirmed that dopamine and its actions in the brain are involved in the subjective experience of reward. Anatomically, the reward system is located deep in the brain in a region called the ventral striatal area, with nerve fibers projecting to an area known as the nucleus accumbens and subsequently to higher regions of the brain. This also is called the mesolimbic dopamine system. Alcohol and other drugs, as well as food or sex, can trigger the release of dopamine in this reward system and reinforce the subjective pleasurable experiences therefore associated with alcohol or the other stimuli and are a component of the reward process. PET studies have allowed researchers to directly investigate the role of dopamine and the reward system in alcohol consumption in humans.

When alcohol induces the release of dopamine in the nucleus accumbens, nerve signals are sent to the cortex, where they are registered as "experience" and memories of the rewarding effects of alcohol, such as its taste or the feelings of relaxation after drinking. Once registered, these memories can stimulate further alcohol intake, completing the reward system. Because memories of the rewarding effects of alcohol also include the environment in which drinking occurred, even sights or smells related to that environment can subsequently trigger the reward system. Indeed, several studies have suggested that alcoholics are predisposed to relapse and that environmental stimuli related to alcohol can trigger the impulse to drink. Animal studies have confirmed that the nucleus accumbens is probably involved in the rewarding aspects of alcohol consumption and also may mediate the stimulatory effects of environmental cues associated with past drinking. Another study using single photon emission computed tomography (SPECT) found that alcoholics ingesting a sip of alcohol during brain imaging showed enhanced neuronal activity in a certain region of the ventral striatal area (a part of the basal ganglia) that correlated highly with their increase in craving. Because alcohol consumption increases dopamine release preferentially in the ventral striatal area, these findings support the view that dopamine activation is a common property of AODs and contributes to their reinforcing effects.

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.