How does alcohol affect the brain?

The exact cause of intoxication at the cellular level is not clearly known. It appears that although alcohol has a wide-ranging effect on the brain, certain brain regions are preferentially more sensitive to alcohol, and certain neurotransmitter systems are involved. The neurotransmitters affected by alcohol include gamma-aminobutyric acid (also known as GABA), glutamate, serotonin, dopamine, and the endogenous opiates. These neurotransmitters are involved in various aspects of alcohol's short- and long-term effects on the brain that include both intoxication but also withdrawal and possibly addiction. Some neurotransmitters are excitatory — that is, they increase the firing rate of nerve cells that would normally fire at a lower rate with a given environmental input — whereas some are inhibitory, or decrease the firing rate of nerve cells in response to a given environmental input.

Transport pump see transporter.

Reuptake the process by which neurotransmitters return to the presynaptic cells after being released into the synaptic cleft and attaching receptors on the postsynaptic cells.

GABA gamma-aminobutyric acid, the brains major inhibitory neurotransmitter. This neurotransmitter dampens all brain activity.

Glutamate the brain's major excitatory neurotransmitter. This neurotransmitter activates all brain activity.

Serotonin one of the brains major neurotransmitters.

Dopamine one of the brain's major neurotransmitters.

Endogenous opiates opioids that develop or originate within the body.

Anticonvulsant a drug that prevents seizures from occurring.

Barbiturates a class of drugs that effect GABA to prevent seizures from occurring. They are used for anxiety disorder until the discovery of benzodiazepines, which were found to be much safer in.

Phénobarbital a barbiturate currently used as an anticonvulsant.

GABA is the brains major inhibitory neurotransmitter. The function of GABA is to inhibit or dampen overall brain activity. Thus, general arousal is dampened, leading to decreased motor tension and anxiety and increased sedation and sleep. GABA also has anticonvulsant activity, which prevents seizures. Alcohol causes GABA to be more potent in the cerebral cortex by altering the GABA receptor in such a way as to make it more attractive to GABA. Most current prescription sedatives (antianxiety inducing) and hypnotics (sleep inducing), such as diazepam and lorazépam, or zolpidem, are medications that act on this neurotransmitter system in a similar manner as alcohol. Barbiturates such as phénobarbital also act on GABA receptors. Additionally, anticonvulsant medications such as valproic acid, gabapentin, and lamotrigine increase GABA activity, though by a different mechanism than the sedative hypnotics. Experimental drugs have been used on laboratory rats that actually block the behavioral manifestations of alcohol intoxication, including sedation and loss of coordination. The lack of signs and symptoms of alcohol use probably occurs because these experimental drugs bind to the GABA receptor blocking alcohol's ability to also bind at the same site.

Glutamate is the brains primary activating neurotransmitter and is another neurotransmitter system that alcohol affects, but it is opposite from GABA. Glutamate has a primary role in learning and memory functions through the alteration of neuronal growth. It can also play a role in nerve cell death when its levels are too high through a process known as excitotoxicity. It also appears to have a role in the development of psychosis and seizures. Glutamates effectiveness is reduced by alcohol's damping effect on its major receptor known as the NMDA receptor (for N-methyl-D-aspartate, the chemical that specifically attaches to that particular glutamate receptor). Acute alcohol use also inhibits the release of glutamate, which in turn impacts on the release of several other neurotransmitters downstream, including dopamine, norepinephrine, and acetylcholine. Chronic alcohol use, on the other hand, potentiates or increases the brains sensitivity to glutamate. This occurs through a process known as upregulation, where the brain is like a thermostat producing more NMDA receptors in order to compensate for alcohol's dampening effects. Upregulation may relate to the effects of tolerance, which means that increasing amounts of alcohol are needed in order to increase GABA further and dampen glutamate. This may also explain withdrawal symptoms, where sudden increases in glutamate activity may account for nerve toxicity leading to hyperactivity, psychosis, and seizures.

Valproic add an anticonvulsant medication that acts on GABA and is FDA approved for use in bipolar disorder (manic depression).

Gabapentin (Neurontin) an anticonvulsant medication that may be used as an adjunct treatment with other drugs for seizures for adults and children over 12 years old.

Lamotrigine generic name for Lamictal — an anticonvulsant.

Excitotoxicity the pathological process by which neurons are damaged and killed by the overactlvation of receptors for the excitatory neurotransmitter glutamate.

Serotonin, a third neurotransmitter, is implicated in alcohol's intoxicating effects. Serotonin plays a role in anxiety, mood, sleep, appetite, and sexual function. Drugs that acutely boost serotonin can cause an alcohol-like high. The hallucinogens, such as LSD, mescaline, and psilocybin, impact the serotonin neurotransmitter system, thus inducing hallucinations and euphoria and also impairing other cognitive functions. Evidence demonstrates that acute alcohol administration increases serotonin activity in the brain as well as impacts various serotonin receptors, increasing the activity of some receptors while decreasing the activity of others. On the other hand, chronic administration of alcohol leads to a decrease in serotonin activity in the brain and causes upregulation of some serotonin receptors that may contribute to the development of some of the symptoms of tolerance and withdrawal when alcohol is abruptly stopped. Particularly symptoms of anxiety, dysphoria, and insomnia often increase. Serotonin may also be responsible for the nausea that people experience from alcohol. Ondansetron, a serotonin receptor blocker, is used as an antiemetic in cancer chemotherapy and may have similar beneficial affects in alcoholism. It appears that the antidepressant medications known as selective serotonin reuptake inhibitors (e.g., fluoxetine) increase serotonin in the brain and decrease drinking behavior in rats who have been selectively bred for alcohol preference and found to have low serotonin. This effect has also been found in humans, although its effects are so modest that they are not clinically useful. Serotonin can also affect other neurotransmitter systems. Serotonin can increase GABA activity, which may contribute to memory loss and cognitive impairment. Serotonin also stimulates the release of dopamine, which also effects attention, concentration, memory, mood, and psychosis.

NMDA (N-methyl-D-aspartic acid) an amino acid derivative acting as a specific agonist at the NMDA receptor.

Norepinephrine a neurotransmitter in the brain as well as a stress hormone released by the adrenal glands.

Acetylcholine the first neurotransmitter discovered.

Potentiates to make more active or effective, to augment, and to make more potent.

Sensitivity probability of a positive test among patients with a particular disease.

Hallucinogen a classification of drugs that produces hallucinations, euphoria, an altered body image, distorted or sharpened visual and auditory perceptions, confusion, loss of motor coordination, and impaired judgment and memory.

Ondansetron generic name for Zofran, an antiemetic drug that acts on specific serotonin receptors.

Antiemetic a drug known for its antinausea and antivomiting qualities.

Opiates, also known as narcotic analgesics, are most commonly thought of as pain medications that are associated with addiction. In the 1970s, it was discovered that opiates attach to very specific opiate receptors in the body and brain that cause analgesia or pain relief. Why would the body have such receptors if it did not also make its own chemicals that fit those receptors? From the findings of this research came the discovery of endogenous opiates known as enkephalins and endorphins. These chemicals cause similar effects on the body as the opiates that are ingested. Alcohol appears to increase an endogenous opiate known as beta- endorphin. Research has demonstrated that mice specifically bred for the lack of a particular opiate receptor have no interest in alcohol. When chemicals are administered that block the beta-endorphin receptor, rendering it dysfunctional, mice decrease their alcohol consumption similarly to those who do not have the receptor to begin with. This research has led to the development of specific treatments (see Questions 49 and 50). It is now recognized that opiate receptors are found on known dopamine pathways in the brain, which suggests that enkephalins and endorphins, when attached to these receptors, also play a role in the release of dopamine.

Selective serotonin reuptake inhibitors (SSRI) a class of antidepressant/antianxiety medication that works by blocking the serotonin transporter.

Fluoxetine the generic name for Prozac, which is a selective serotonin reuptake inhibitor (SSRI).

Opiate a type of opioid.

Dopamine is a major neurotransmitter associated with the brain's reward system (Figure 4), but it also plays a role in attention and concentration, involuntary movements, and hallucinations. Alcohol boosts dopamine in the brain, leading to euphoria and possibly contributing to addiction. Increasing scientific evidence suggests that all drugs of abuse, including nicotine, boost dopamine to one degree or another; however, in experimental studies with laboratory animals, selectively knocking out these specific dopamine pathways affects the quality of alcohol administration but not the various reinforcers that prompt the animal to continue to self-administrator. Table 1 lists the various neurotransmitters and alcohol's effect on the various neurotransmitter systems.

Figure 4 Limbic areas involved with mood and reward. From Used with permission. Copyright © 1999 Scientific Learning Corporation. All rights reserved.

Narcotic analgesic an opioid used to control pain.

Enkephalins an endogenous opioid made up of amino adds. They are produced in the brain and have an affinity for opiate receptor sites, acting similarly to analgesics and opiates.

Endorphins short for endogenous morphine. See enkephalin or endogenous opiate.

Vertigo dizziness, as in the room is spinning around. This is a brain effect as opposed to lightheadedness or feeling faint, which is due to low blood pressure.

Mellanby effect impairment from alcohol is greater at a given blood alcohol level when the amount of alcohol in the blood is increasing as opposed to decreasing. This also explains the differences in feeling "hung over" as opposed to "buzzed" at the same alcohol level depending on a falling or rising level.

The intoxicating effect of alcohol generally correlates with the amount of alcohol in the blood. In persons who are not alcoholic, blood alcohol concentrations of 25 mg per deciliter indicate mild intoxication manifested by alterations in mood, thought, and motor control. At levels above 100 mg per deciliter, signs of vertigo, double vision, slurred speech, and unsteady gait increase. The legal limit was 100 mg per deciliter, but most states have adopted the more conservative limit of 80 mg per deciliter to meet the guidelines for federal highway funding; however, studies demonstrate that levels even as low as 47 mg per deciliter are associated with an increased risk of involvement in motor vehicle accidents. Blood alcohol levels of 500 mg per deciliter or greater may lead to respiratory arrest and death. Several modifying variables can influence the outcomes. At the same concentration, a rising blood level of alcohol causes greater intoxication than a falling blood level. This is known as the Mellanby effect. Chronic alcohol use can lead to tolerance so that intoxication occurs at much higher levels than mentioned previously here, and patients with blood alcohol levels of 500 mg per deciliter are commonly seen in emergency rooms without clinically significant respiratory distress.

Table 1 Alcohol's Effects on Neurotransmitter Systems

• Effects on the dopamine system

-Increase dopamine in mesocorticolimbic system -Reinforcing, rewarding effects

• Effects on the opioid peptide system

-Activation of opioid peptide system -Reinforcing and rewarding effects (Mu) -Aversion (Kappa)


• Effects on NMDA glutamate system

-Blockage of NMDA receptor (allosteric effect) -Sedative/hypnotic effects -Neuroadaptation -Withdrawal

• Effects on the serotonin system

-Neuroadaptation aversion -Depression, anxiety

• Effects on stress hormones

-Stress response (fight or flight)

-Increased epinephrine and norepinephrine


Transmitter/Receptor I


Dopamine, Opioids












GABA, NMDA (↑Ca, ↓Mg)

American Society of Addiction Medicine (ASAM) established in 1989, was the first American medical society to focus on drugs and alcohol.

Reinforcers the stimuli that are coupled with a behavior in operant conditioning that are either applied or removed to elicit the desired response.

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