Author: Alex Thompson

Alcohol and Dopamine Does Alcohol Release Dopamine?

Both dopaminergic and nondopaminergic neurons also carry dopamine receptors that are located on the nerve terminals outside the synapse (i.e., are extrasynaptic). Dopamine that has been released from a nerve terminal into the synaptic cleft can travel out of the synapse into the fluid surrounding the neurons and activate these extrasynaptic receptors. Through this mechanism, dopamine modulates the neurotransmitter release that is induced by cellular excitation (i.e., neurotransmitter secretion).

1. This article suggests mechanisms by which alcohol consumption may affect multiple neurotransmitter systems to influence behavior.
2. In addition to dementia, long-term alcohol use can lead to other memory disorders like Korsakoff syndrome or Wernicke’s encephalopathy.
3. For example, serotonin can increase the activity of GABAergic neurons in the hippocampal formation (Kawa 1994), a part of the brain that is important for memory formation and other cognitive functions.
4. For definitions of technical terms used in this article, see central glossary, pp. 177–179.

Long-term effects

An important finding is the demonstration that alcohol can affect the function of specific neurotransmitters1 (Lovinger et al. 1989). Studies of neurotransmitters and the receptors to which they bind have provided data on both the structure and the mechanism of action of these molecules as well as clues to their role in behavior. However, the function of individual neurotransmitters and their receptors cannot entirely explain a syndrome as complex as alcoholism. A large body of evidence indicates that dopamine plays an important role in motivation and reinforcement6 (Wise 1982; Robbins et al. 1989; Di Chiara 1995). These factors include (1) the type of stimuli that activate dopaminergic neurons, (2) the specific brain area(s) affected by dopamine, and (3) the mode of dopaminergic neurotransmission (i.e., whether phasic-synaptic or tonic-nonsynaptic). To modulate the responsiveness of neighboring neurons to glutamate, dopamine modifies the function of ion channels in the membrane of the signal-receiving (i.e., postsynaptic) neuron.

Neurotransmitter Systems Work Together

For example, in some neurons serotonin alters the rate at which the cells produce the electrical signals (i.e., action potentials) used for relaying information within the cells, whereas in other neurons it modulates the release of other neurotransmitters. Long-term, or chronic, alcohol exposure2 can lead to adaptive changes within brain cells. This process, also called tolerance development, presumably is a mechanism to reestablish normal cell function, or homeostasis, in response to continuous alcohol-induced alterations. Thus, the number of 5-HT2 receptor molecules and the chemical signals produced by the activation of this receptor increase in laboratory animals that receive alcohol for several weeks. Serotonin is produced in and released from neurons that originate within discrete regions, or nuclei, in the brain (Cooper et al. 1991). Many serotonergic neurons are located at the base of the brain in an area known as the raphe nucleus, which influences brain functions related to attention, emotion, and motivation.

An example of such behavior is tolerance (i.e., a person must drink progressively more alcohol to obtain a given effect on brain function). For example, in animals exposed for several days to alcohol, many neurotransmitter receptors appear resistant to the short-term actions of alcohol on glutamate and GABAA receptors compared with animals that have not been exposed to alcohol (Valenzuela and Harris 1997). An example of such interaction occurs in Purkinje cells, a type of neuron found in the cerebellum. In these cells, the increased activation of the GABAA receptor induced by alcohol occurs only with concurrent activation of certain receptors for norepinephrine, a neurotransmitter with many regulatory functions (Lin et al. 1993). Interestingly, alcohol also acts on some receptors for norepinephrine (LeMarquand et al. 1994; Tabakoff and Hoffman 1996; Valenzuela and Harris 1997). Serotonin may interact with GABA-mediated signal transmission by exciting the neurons that produce and secrete GABA (i.e., GABAergic neurons).

Alcohol might also increase inhibitory neurotransmission by increasing the activity of inhibitory neuromodulators, such as adenosine. Activation of the adenosine system causes sedation, whereas inhibition of this system causes stimulation. Stimulants that inhibit the actions of adenosine include caffeine as well as theophylline, a chemical found in tea. Animal studies have shown that caffeine and theophylline reduce the sedative and motor-incoordinating effects of alcohol (Dunwiddie 1995), although these substances do not alleviate symptoms of intoxication in humans. Biochemical evidence indicates that short-term exposure to alcohol of nerve cell cultures in the laboratory increases the levels of adenosine that can interact with adenosine receptors. Thus, an alcohol-induced increase in adenosine levels might be responsible for part of alcohol’s sedative actions.

Alcohol Withdrawal Syndrome

For example, serotonin can increase the activity of GABAergic neurons in the hippocampal formation (Kawa 1994), a part of the brain that is important for memory formation and other cognitive functions. Consequently, alcohol’s effects on serotonin may alter the activity of GABAergic neurons in the hippocampal formation. These changes may disrupt cognition and possibly contribute to alcohol-induced memory loss and impaired judgment. Other lines of research related to alcohol withdrawal reinforce this model of alcohol-related changes in DA. Although numerous studies have attempted to clarify dopamine’s role in alcohol reinforcement by manipulating dopaminergic signal transmission, these investigations do not allow any firm conclusions (for a review, see Di Chiara 1995).

Effects of Short-Term Alcohol Consumption

Both positive and negative reinforcement play a role in alcoholism (Koob et al. 1994). The major excitatory neurotransmitters in the brain are the amino acids aspartate and glutamate, which act through both NMDA receptors—so named because they respond to the synthetic chemical N-methyl-d-aspartate—and non-NMDA receptors. Short-term exposure to intoxicating concentrations of alcohol appears to inhibit both NMDA and non-NMDA receptor activity, potentially resulting in sedation (Valenzuela and Harris 1997).

These varying results may be due to the use of different animal models or different research protocols. Alcohol-induced changes in brain functions can lead to disordered cognitive functioning, disrupted emotions and behavioral changes. Moreover, these brain changes are important contributing factors to the development of alcohol use disorders, including acute intoxication, long-term misuse and dependence. These examples demonstrate that serotonin interacts with other neurotransmitters in several ways to promote alcohol’s intoxicating and rewarding effects.

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Instead, serotonergic neurons are parts of larger circuits of interconnected neurons that transmit information within and among brain regions. Accordingly, some of the serotonin-mediated neuronal responses to alcohol may arise from interactions between serotonin and other neurotransmitters. Two key neurotransmitters that interact with the serotonergic system are gamma-aminobutyric acid (GABA) and dopamine.

Although neurons communicate with one another chemically, signals travel through a neuron in the form of an electric current. By breeding rats with similar alcohol-consumption patterns (e.g., high consumption or low consumption) with each other for several generations, researchers created two strains with distinctly different preferences for alcohol. “If you’re using alcohol to cope with stress or anxiety, if you’re going out and intending to drink one drink and you’re not able to stop yourself from drinking, it’s important to talk to your doctor and meet with a specialist,” encourages Dr. Anand. These effects can happen even after one drink — and increase with every drink you have, states Dr. Anand. But as you drink more — and you don’t need to drink that much more — eventually, the enzymes that break down the alcohol get saturated. So, the alcohol builds up quite quickly,” explains addiction psychiatrist Akhil Anand, MD.