DO ALL PARTS OF THE BRAIN LEARN?

DO ALL PARTS OF THE BRAIN LEARN?

The processes that we just described do not happen in just one part of the brain. There are indeed specialized neural networks, especially in a part of the brain called the hippocampus, where learning occurs and memo­ries are created. (People who have had damage to this part of the brain cannot learn new things, although they can remember things that happened before.) However, most forms of plasticity can occur all over the brain and affect all brain function.

For us to be able to function normally, all brain processes need to pro­ceed unimpaired. All of the neurotransmitter systems need to be working.

The brain needs to change with time to reflect previous experience—that is, learn—to restore balance if it is over- or understimulated.

THE DEVELOPING BRAIN

While the brains of adults change all the time, what goes on in adults is trivial compared to the phenomenal changes that occur while the brain is developing. The brain assembles itself carefully through the process of neurons growing out, and through chemical signals around them, gradu­ally finding their way to the correct destination, where they make the connections that they then maintain. During this time of life, the physi­cal changes in the brain are dramatic. New synaptic connections are being made at a high rate every day. The growing brain also has its own way of "forgetting." Many of the neurons growing out never reach their destination and die in the process. Others reshape their connections until they are correct. Through all of this furious growth, neurons must remain active or they can fail to make their appropriate connections. Therefore, changes in neuronal function that in an adult would simply shut down a pathway for a while, in a developing brain can have more drastic consequences.

Growing neurons are affected by processes that don't affect the neurons of adult brains. Exposure to substances that inhibit cell growth has some impact on an adult brain but a devastating impact on the developing brain. The neurotoxic element mercury provides a good example. Mer­cury affects the function of the adult brain and can lead to serious, but largely reversible, disruption of brain function. However, exposure of the brain of the developing fetus to mercury disrupts brain development so totally that severe mental retardation results. For example, an industrial spill of mercury into the water near a small, coastal Japanese town called Minamata contaminated the fish that were the local food source. While many adults experienced diseases that eventually resolved, many children born during this time frame had terrible disruption of normal brain development and remained mentally retarded throughout their lives.

Recently, medical imaging techniques have made it possible to study the development of the human brain at various points from birth to adulthood. Some of the most interesting studies use magnetic resonance imaging (MRI) with the machine set to reveal the white matter of the brain, the myelin insulation on the nerve cell axons. As the brain matures, the connections between cells become permanent, and then they are insulated with myelin. So, imaging for the myelin tells the scientist just how much development has occurred in a brain area. The big news is that the human brain is not fully developed until late in adolescence. And among the last parts to develop are the frontal lobe areas that give us the capability of inhibiting inappropriate behavior, handling complex tasks, and planning ahead. When we lecture about this, we often make the point that from the standpoint of the brain, adolescents are not "young adults," but rather, "big kids,"

We believe it is very important to teach kids that their brains are still developing through adolescence. This means that they have the opportu‑  when we were drunk (see the "Alcohol" chapter for more information). presses maze learning. So, now we may know why we forget what we did are also suppressed in humans.

injury. There is every reason to believe that learning and neuroplasticity and the CNS does not reorganize its neuronal connections following glutamate cannot bind there, LIP does not occur, rats do not learn mazes, oratory experiments, if we chemically block the NMDA receptor so that how memory occurs and how some drugs disrupt it. For example, in lab-learning and other forms of neuroplasticity. It may teach us much about receptor, because it appears to be one of the most important receptors for strengthening that synapse.

the NMDA receptor is activated, the cell "remembers" the signal by receptor is like a memory switch. When the cell is receiving a signal and The calcium causes LTP to occur at those synapses. Thus, the NMDA Many drugs affect the ability of the brain to learn—there is no question only when the cell is receiving excitatory signals through other synapses. receptor, has the very special property of letting calcium into the cell mate. This particular subtype, the NMDA (the N-methyl-D-aspartate) Alcohol in rats blocks NMDA receptors, suppresses LTP, and sup 

presses blocks a certain subtype of the excitatory neurotransmitter gluta¬manifestations about it. But which drugs have which effects, and for how long? One of the best stories about the effects of drugs on learning was told to one of us by a drug company representative during an airplane trip. It seems that some of the professional staff from his company were making a quick trip over­seas to a meeting, and they needed to sleep during the plane ride because their lectures were scheduled almost as soon as they were to arrive. So, this group had a few alcoholic drinks and then took one of their newly marketed sedatives (a benzodiazepine) to get to sleep. Everything went well, including the lectures, and the scientists returned home in a couple of days. The only problem was that when they returned, they remembered nothing of the meeting—not their lectures or those of anyone else. They

did not know that the drug they chose, in the dose they chose, would have

powerful amnesiac effects, especially when mixed with alcohol. This story is legend in the pharmaceutical industry, and whether it is exactly true does not make any difference. It illustrates the point that even the people who develop and manufacture drugs by the highest standards may not know every effect they can have and how long these effects can last.

There are basically three ways in which drugs can affect learning: they can impair the ability of the brain to store information (amnesia), they' can distort reality, or in some cases, they can stimulate the brain to

increase learning.

By far the most common effect of drugs is to suppress learning. Almost

all of the drugs that have sedative or anxiety-reducing properties impair the retention of information. Although we do not know exactly how this happens, there are three mechanisms that have been proposed at the syn‑

aptic level.

The first of these is increased inhibition. We know that many sedative drugs increase GABA-mediated synaptic activity, which inhibits the fir­ing of neurons. The experimental data suggest that this increase in inhibi­tion can reduce the effects of the type of neuronal firing that is usually necessary for LTP, and thus prevent neuroplasticity.

The second of these mechanisms is reduced excitation. Some drugs, such as alcohol, not only increase GABA function (and thus inhibition) but also suppress the glutamate-mediated excitatory channels (the NNIDA receptor channels) that let calcium ions into the neurons. This reduction in calcium entry prevents the signaling mechanisms within the neurons that lead to long-term synaptic changes.

Finally, there are drugs, such as the THC in marijuana, that act through their own receptors to change cell biochemistry so that learning is   impaired. From what we know of their biochemistry, they may directly

regulate the signal-processing pathways within the cell that govern the strength of synaptic activity, perhaps by suppressing the signals thatmediate LTP or, alternatively, by enhancing the processes underlying LTD and/or depotentiation.

Now that we know about LTD and depotentiation, it is easy to imagine that there would be reasons for the CNS to reduce activity in some path‑

ways and thus "forget" some neuroplastic changes. Therefore, it is com‑

pletely reasonable that some drugs could enhance this type of signaling, reducing the ability to learn.

On a brighter note, neurobiologists are exploring ways to use drug therapy to enhance learning. This research is particularly important for the many people who suffer from Alzheimer's disease or other brain dis­orders that impair learning. Most of the rest of us would also relish the

ability to learn more or faster. There are some tantalizing clues that this may be possible.

One of the most interesting clues comes from an experience that almost all of us have had. It's the "Do you remember what you were

doing when ... ?" question. Every generation has at least one of these ques‑

tions. For older people, it's what they were doing when they heard that JFK

was assassinated. Nearly everyone recalls the fateful morning of 9/11. Think

of an example: the first time you had a very important and emotional expe­rience, either positive or negative.

Why is it that we remember some experiences so well, and not only the event but maybe what clothes we wore, what the room looked like, what we ate? Ongoing experiments shed a lot of light on this phenomenon. Dr. James McGaugh (of the University of California at Irvine) took two similar groups of people and placed them in separate but similar rooms with all sorts of cues, or decorations. The goal was to subject the groups to an

emotional story and to see how well they remembered the story and the environment (the room) in which they experienced the event.

What makes this experiment interesting is that one group was given a drug (propranolol) that blocks a particular subtype of adrenaline recep‑

tor—the beta-adrenaline receptor. This receptor is the one responsible for the increase in heart rate and blood pressure that occurs under physical or emotional stress; the blocker, propranolol, is used to control blood pressure and heart problems in some patients. So, one group was com‑

pletely normal, while the other group had their excitatory adrenaline activity blocked.  The experimental subjects were then told a heartbreaking story about an injured child. After a period of time the two groups were removed from their rooms and then asked to recall the story and the details of their environment in the room. Both groups remembered the story. How­ever, only the normal (undrugged) group remembered the details of the room. The treated group remembered very little of their environment.

What does this teach us? We all know that we tend to learn what inter­ests us, and we know that we remember emotional events. Now we know why. The adrenergic system apparently delivers signals to the brain that facilitate learning and remembering the environment associated with an emotionally powerful event. This is probably a very important character­istic for both humans and other animals to have, because it tends to help us remember events and places that were either wonderful or threatening, and thus adjust our future behavior accordingly. So, now it is clear why a smell or a face or a place might make you feel good or bad, even if you cannot immediately recall why: your brain is recalling an emotional

experience.

This insight into learning is useful in several ways. First, it illustrates how important it is to be alert and interested in what we are trying to learn. When we are sleepy or depressed we are poor learners, in part because our adrenergic system is not activated. To really learn or teach something, we must include an emotional component.

In addition, this experiment suggests that there may be ways to facili­tate learning through manipulating brain chemistry. Neuroscientists already know that the adrenergic system is not the only modulator of learning. However, increasing the function of any of these systems has proven difficult to achieve without producing unacceptable side effects.

At this point, no drug has yet been approved to increase learning. Until then, readers, you'll have to "trick" your brain by studying what is excit­ing and by getting excited about what you must study!

Acohol Dependence

It is important to distinguish between alcohol dependence and alcohol abuse. Generally, alcohol abuse refers to patterns of drinking that give rise to health problems, social problems, or both. Alcohol dependence (often called alcoholism) refers to a disease that is characterized by abnormal seeking and consumption of alcohol that leads to a lack of control over drinking. Dependent individuals often appear to crave alcohol. They seem driven to drink even though they know that their drinking is causing problems for them. The signs of physical depen­dence begin within hours after an individual stops drinking. They include anxiety, tremors (shaking), sleep disturbances, and, in more extreme cases, hallucinations and seizures. Until a chronic drinker actually stops drinking, it is quite difficult to make a definitive assess­ment of alcohol dependence. But for most practical purposes, this for­mal diagnosis is unnecessary, because the social and medical problems that most alcoholics experience should be recognizable to health profes­sionals. See the section "How to Spot a Problem Drinker" on page 55 for some general guidelines.

PRENATAL EXPOSURE

The dangers of prenatal alcohol exposure have been noted since the time of Aristotle in ancient Greece. However, it was not until 1968 that formal reports began to emerge. The early studies of fetal alcohol syndrome (FAS) described gross physical deformities and profound mental retarda­tion among children of heavy-drinking alcoholic mothers. Although this was a very important set of findings, at first there was no evidence that women who drank more moderately were placing their children at risk. In fact, for many years, pregnant women were often encouraged to have a glass of wine with dinner or take a drink now and then during pregnancy to help them fall asleep or just to relax.

It took a while for the effects of moderate prenatal drinking to be noticed, because the children have none of the very obvious defects asso­ciated with the full-blown fetal alcohol syndrome. However, it is now clear that there is a less severe, but very well documented, pattern of defi­cits associated with more moderate prenatal drinking—a pattern described as fetal alcohol effects (FAE). School-age children with FAS or FAE are frequently described as hyperactive, distractible, and impulsive, with short attention spans—behaviors similar to those observed in chil­dren with attention deficit disorder (ADD). However, the FAS and FAR children differ from ADD children in that they are more intellectually

impaired. In recent years the term fetal alcohol spectrum disorders (FASD) has emerged as an umbrella term to include the full range of neurological, cognitive, behavioral, and learning disabilities associated with prenatal alcohol exposure.

The impairments of intelligence and behavior in people with FASD appear to persist into adulthood and are probably lifelong, resulting in IQ scores markedly below average, often well into the moderately retarded range. Those with PAS scored worse than those with RAE, but both were significantly below normal, hampered in reading and spell­ing and most profoundly deficient in mathematical skills. More import­ant, the FAE patients did not perform any better than the FAS patients on academic achievement tests, though their IQs were somewhat higher. What all this means is that even moderate drinking during pregnancy can create permanent intellectual disabilities. Some studies using animal models of FAE even suggest that just one drink per day impairs the function of brain areas related to learning in the adult offspring.

The bottom line is that there is no identified safe level of drinking during pregnancy. The smart decision for a woman is simply not to drink if she is pregnant or thinks that she might be.

What about Social Drinkers

     What about "Social Drinkers"?

It is important to define exactly what we mean when we say that someone is a social drinker. The most consistent definition, looking across the liter­ature on alcohol use and treatment, would be this: someone who drinks regularly but does not get drunk when he drinks or have any of the clini­cal signs of addiction to alcohol. People who fit this pattern of drinking generally do not have nearly as severe deficits in mental functioning as those who drink heavily.

Among social drinkers, the pattern of alcohol consumption plays a very important role in determining whether the person will develop deficits in mental functioning. The more alcohol he drinks during each drinking session, the higher the likelihood that mental deficits will develop. Consider two people who each drink five drinks per week, on average. The first person has one drink on each of the five days of the week, and the second person has four drinks on each Saturday night and one in the middle of each week. The second person will be more likely to develop the kinds of deficits in the aforementioned abilities for chronic alcoholics. This is a particularly important point for young people, because heavy drinking on weekends is a typical pattern for

many high school and college students as well as for young people in the work world.

It is difficult to say what amount of drinking over time will result in deficits in mental function. There have been many studies addressing this issue in different groups of people, and it's very hard to boil all of these down to a clear and concise statement of risk. However, when all the complexities of the research are taken into consideration, it is rea­sonable to estimate that people who drink three or more drinks per day on average are at substantial risk of developing permanent deficits in certain cognitive abilities. This is not to say that drinking less is per‑fectly safe—indeed, we know that there are health risks associated with drinking less—but in terms of causing irreversible cognitive deficits, three drinks per day appears to be something of a threshold.

Tolerance

Development across Several Drinking Sessions

Tolerance means that after continued drinking, consuming an identical amount of alcohol produces a lesser effect—in other words, more alcohol is necessary to produce the original effect. The development of tolerance indicates that alcohol exposure has changed the brain. In some ways it is less sensitive to the alcohol, but in other ways it may remain quite sensi­tive. The brain effects that produce the high may diminish, while the effects that are toxic to the brain cells themselves may remain the same. Another problem is that as tolerance develops, the drinker may drink more each time to get the high. As we just learned, such a drinking pat­tern is more likely to produce deficits in mental functioning over time. Also, because the brain is the organ of addiction, the tolerant person who increases her drinking runs a greater risk of addiction. Finally, although the brain may need more alcohol to produce the high, the liver and other internal organs are dealing with more and more alcohol, and they are at risk for permanent damage.

Development within One Drinking Session

Although tolerance to most alcohol effects develops gradually and over several drinking sessions, it has also been observed even within a single drinking session. This is called acute tolerance and means that the intoxi­cation is greatest soon after the beginning of drinking. Acute tolerance does not develop to all the effects of alcohol, but it does develop to the feeling of being high. So, the drinker may drink more to maintain the feeling of being high, while the other intoxicating effects of alcohol (those that interfere with driving, mental function, and judgment) continue to build, placing the drinker at greater and greater risk.

Chronic Alcohol Abuse

Effects on Mental Functioning

Five areas of mental ability are consistently compromised by chronic alcohol abuse: memory formation, abstract thinking, problem solving,attention and concentration, and perception of emotion. As many as 70 percent of people who seek treatment for alcohol-related problems suffer significant impairment of these abilities.

Memory Formation

By memory formation we mean the ability to form new memories, not the ability to recall information that was learned in the past. That is, an individual with a chronic drinking habit might vividly and accurately recall what he learned early in life but not be able to tell what he ate for lunch four hours ago. And the richness and detail of his memories during the past few years of drinking might be significantly less than in those earlier memories. On some tests of mental ability that assess differ­ent kinds of brain functions, chronic drinkers often perform lust fine on most of the categories but perform poorly on the memory sections. This selective and profound memory deficit may be a result of damage to spe­cific brain areas, such as the hippocampus, the mammillary bodies, or the frontal lobes.

Abstract Thinking

By abstract thinking we mean being able to think in ways that are not directly tied to concrete things. We think abstractly when we interpret the meaning of stories, work on word puzzles, or solve geometry or alge­bra problems. Chronic drinkers often find these abilities compromised. One way to measure abstract thinking is to show someone a group of objects and ask her to group the objects according to the characteristics they share. Chronic drinkers will consistently group things based on their concrete characteristics (such as size, shape, and color) rather than on the basis of their abstract characteristics (such as what they are used for, or what kinds of things they are). It is as if abstract thoughts do not come to mind as easily for the chronic drinker.

Problem Solving

We all have to solve problems each day. Some are simple ones, like deter­mining whether to do the laundry or the grocery shopping first. Some are more complicated, like setting up a new personal computer or deciding on what inventory to order for the next month's needs in a business. In either case, one of the required abilities is mental flexibility. We need to be

able to switch strategies and approaches to problems (particularly the complicated ones) to solve them efficiently. People with a history of chronic drinking often have a lot of difficulty with this. Under testing conditions, it often appears that they get stuck in a particular mode of problem solving and take a lot longer to get to a solution than someone who is better able to switch strategies and try new approaches. This diffi­culty could relate to the effects of chronic drinking on the "executive functions" of the frontal lobes.

Attention and Concentration

Chronic drinkers also develop difficulty in focusing their attention and maintaining concentration. This appears to be particularly difficult when related to tasks that require visual attention and concentration. Again, the deficits may not appear until the person is challenged. In casual conversa­tion, the sober chronic drinker may be able to concentrate perfectly well, but placed in a more challenging situation (like reading an instruction manual, driving a car, or operating a piece of equipment), she may be quite impaired.

Perception of Emotion

One of the most important elements of our social behavior is the ability to recognize and interpret the emotions of other people. Alcoholics have a deficit in the ability to perceive emotion in people's language. There is a specific brain function that normally gives us the ability to detect attitude and emotion in conversation. It turns out that chronic, heavy drinking markedly reduces this ability. It is important to realize that this deficit is one of perception and does not reflect the alcoholic's own emotional state. It's as if the subtle things like the tone and cadences of the other person's language that convey attitude and emotion are simply not perceived by the alcoholic. This is particularly interesting because we know that chronic heavy drinkers often have difficulty in social relationships. Per­haps this perceptual deficit causes some of these problems.

Do These Deficits Go Away?

Chronic heavy drinkers who quit recover these functions partially during the first month or two after the last drink. However, once this

time passes, they have gotten back all that they will recover. It is difficult to identify precisely how much recovery occurs, but clear deficits do appear to persist permanently in these individuals. In one study, people who had quit drinking completely after many years of alcohol abuse were examined for seven years. Even after this time they had significant memory deficits. This persistent pattern of memory deficits in previous alcoholics is common enough to have a specific diagnosis. It is generally

called either alcohol amnestic disorder or dementia associated with alcoholism.

SCOTT SWARTZWELDER

Short Term Effects Of Alcohol On The Brain

Brain-imaging techniques create a window into the effects of alcohol on the brain. Using these techniques, researchers have observed shrinkage of brain tissue in people after long-term use of alcohol. But there is also recovery of brain tissue volume in people who stop drinking and remain abstinent, so this "shrinking" effect appears not to be due exclusively to the loss of brain cells. Interestingly, some studies indicate that certain parts of the brain may be more vulnerable to damage by alcohol than others, such as the cortex—the folded, lumpy surface of the brain (it gets its name because of its resemblance to the bark of a tree), which endows us with consciousness and controls most of our mental functions. One region of the cortex that appears to be particularly vulnerable is the frontal lobe. The frontal lobes are unique in that they act like a kind of executive manager for the rest of the brain. They monitor and help to coordinate the actions of the other cortical lobes—much like an execu­tive does in a corporation. The analogy is so apt that the functions of the frontal lobes are often called "executive functions." They endow us with the ability to bring together our mental abilities to solve complex prob­lems, to make and execute plans of action, and to use judgment in ser­vice of those plans. Even in people who have never been diagnosed with an alcohol use disorder, chronic drinking can contribute to frontal lobe damage. Another vulnerable region is the mammillary bodies, which are very important for memory. (These small, round structures near the base of the brain got their name from the neuroanatomists who first noticed them and thought that they looked like breasts. Actually, their resemblance to breasts is quite remote, but neuroanatomists do have good imaginations!)

Although many of the studies of brain shrinkage have been done with alcoholics, some of the more recent ones have assessed social drinkers and found similar effects, though less severe. The shrinkage occurs while the person is still using alcohol. If she stops drinking for a prolonged period, her brain will recover somewhat—not because new nerve cells grow but because support cells, or parts of the remaining nerve cells, grow. Therefore, the regrowth of brain size does not mean that the deficits in mental functioning that many alcoholics experience will be erased simply by abstaining from alcohol.

It is not known if there is a safe level of chronic drinking. Clearly many people who drink do not appear to suffer any damage to their mental functioning. Still, as with acute intoxication, the lack of any obvi­ous impairment does not mean that there is none. Studies using animals instead of humans can look more closely at nerve-cell damage. Such studies have shown that more moderate alcohol exposure can damage and kill brain cells. A number of these studies have shown large areas of nerve-cell loss in a region of the brain called the hippocampus, which is known to be critical for the formation of new memories. This could be one reason why people who drink chronically can end up with relatively poor memory function, though of course this will vary with the person's drinking history.

Another study in animals has shown that in the case of very heavy drinking, brain damage may occur much sooner than previously thought. Using a model in which animals are exposed to a heavy "binge" of alcohol around the clock for four days, it was discovered that cells in some of these same regions started to die off after the first two days of the binge. If this holds true for humans, it will show that even one very heavy episode of binging across a couple of days could damage the brain. These effects were

          particularly pronounced in adolescent animals, raising some concern that teenage binge drinking may have more serious long-term consequences than we once thought.

                                                                                                                                                 
                           Wilke Wilsion

BRAIN AND BEHAVIOR

Once alcohol has been absorbed and distributed, it has many different effects on the brain and behavior. To a large extent these effects vary with the pattern of drinking. Therefore, we discuss the effects of acute, chronic, and prenatal alcohol exposure separately.

ACUTE EXPOSURE

Effects on Behavior and Physical State

Although the effects that a given dose of alcohol will have on an individ­ual vary considerably, the following table shows the general effects of a range of alcohol doses:

Still, there is often a substantial difference between being impaired and appearing impaired. In one study, trained observers were asked to rate whether a person was intoxicated after drinking. At low blood alcohol con­centrations (about half the legal limit for intoxication), only about 10 per­cent of the drinkers appeared intoxicated, and at very high concentrations (greater than twice the legal limit), all of the drinkers appeared intoxicated. However, only 64 percent of people who had blood alcohol concentrations of 100-150 mg/100 ml (well above the legal limit in most states) were judged to be intoxicated. So, in casual social interactions, many people who are significantly impaired—and who would pose a real threat behind the wheel of a car—may not appear impaired even to trained observers.

Alcohol and Brain Cells

You've probably heard some variation of the following statement: "Every time you take a drink of alcohol you kill ten thousand brain cells." Although it is highly unlikely that anyone would drink enough alcohol in a given sitting to kill brain cells directly, as with many such generaliza­tions there is a grain of truth in the warning.

One way that researchers have tried to determine which brain regions control which behaviors in animals is by destroying, or lesioning, a specific brain region and then testing the animal on a particular behavioral task.

Early in the use of this lesioning technique, some researchers found that if they injected a very high concentration of alcohol into the brain (far higher than would be achieved by a drinking person), the cells in that region would die. There is also another grain of truth in the warning about alcohol and brain cells: chronic, repeated drinking damages and sometimes kills the cells in specific brain areas. And it turns out that it might not take a very long history of heavy drinking to do so. We will address this in the "Chronic Exposure" section of this chapter.

There are fundamentally only two types of actions that a chemical can have on nerve cells—excitatory or inhibitory. That is, a drug can either increase or decrease the probability that a given cell will become active and communicate with the other cells to which it is connected. Alcohol generally depresses this type of communication, or synaptic activity, and thus its actions are similar to those of other sedative drugs, like barbiturates (such as phenobarbital) and benzodiazepines (such as Valium). Despite this general suppression of neuronal activ­ity, however, many people report that alcohol activates or stimulates them, particularly soon after drinking, when the concentration of alcohol in the blood is increasing. Although we don't know exactly why alcohol produces feelings of stimulation, there are a couple of possibilities. First, there is the biphasic action of alcohol. This refers to the fact that at low concentrations alcohol actually activates some nerve cells. As the alcohol concentration increases, however, these same cells decrease their firing rates and their activity becomes sup­pressed. Or it might be that some nerve cells send excitatory signals to the other cells with which they communicate, prompting them to send inhibitory messages, actually suppressing the activity of the next cell in the circuit. So, if alcohol suppresses the activity of one of these "inhibitory" cells, the net effect in the circuit would be one of activa­tion. Whatever the exact mechanism, it appears that there are several ways in which alcohol can have activating as well as suppressing effects on neural circuits.

Effects on Specific Neurotransmitters GABA and Glutamate

For many years it was generally thought that alcohol treated all nerve cells equally, simply inhibiting their activity by disturbing the structure of the membrane that surrounds each cell. In this sense the effects of alcohol on the brain were thought to be very nonspecific. However, it is now clear that alcohol has specific and powerful effects on the function of at least two particular types of neuronal receptors: GABA receptors and glutamate receptors. GABA and glutamate are chemical neu­rotransmitters that account for much of the inhibitory and excitatory activity in the brain. When the terminals of one cell release GABA onto GABA receptors on the next cell, that cell becomes less active. When glutamate lands on a glutamate receptor, that cell becomes more active. It is in this way that many circuits in the brain maintain the delicate balance between excitation and inhibition. Small shifts in this balance can change the activity of the circuits and, ultimately, the functioning

of the brain.

Alcohol increases the inhibitory activity of GABA receptors and decreases the excitatory activity of glutamate receptors. These are the two primary ways alcohol suppresses brain activity. While the enhance­ment of GABA activity is probably responsible for many of the general sedating effects of alcohol, the suppression of glutamate activity may have a more specific effect: impairment in the ability to form new memo­ries or think in complex ways while intoxicated. We know that the activ­ity of a particular subtype of glutamate receptor, called the NIVIDA receptor, is very powerfully inhibited by alcohol—even in very low doses. The NMDA receptor is also known to be critical for the formation of new memory. Alcohol's powerful suppression of activity at the NMDA recep­tor may therefore account Mr the memory deficits that people experience after drinking. Dopamine

The neurotransmitter dopamine is known to underlie the rewarding effects of such highly addictive drugs as cocaine and amphetamine. In fact, dopamine is thought to be the main chemical messenger in the reward centers of the brain, which promote the experience of pleasure. Alcohol drinking increases the release of dopamine in these reward cen­ters, probably through the action of GABA neurons, which connect to the dopamine neurons. Studies in animals show that the increase in dopa­mine activity occurs only while the concentration of alcohol in the blood is rising—not while it is falling. So, during the first minutes after drinking the pleasure circuits in the brain are activated, but this "dopamine rush"

disappears after the alcohol level stops rising. This may motivate the drinker to consume more alcohol to start the pleasure sequence again—"chasing the high." The problem is that although the dopamine rush is over, there is still plenty of alcohol in the body. Continued drink­ing in pursuit of the pleasure signals could push the blood alcohol con­centration up to dangerous levels.

Effects on Memory

One of the most common experiences people report after drinking is a failure to remember accurately what happened "the night before." In more extreme cases, after heavy drinking, people often report that whole chunks of time simply appear to be blank, with no memory at all having been recorded. This type of memory impairment is often called a "blackout." (Less extreme versions of this type of memory loss have been called "brown outs" or "gray outs," in which the person may have only very hazy or incomplete memory for the events that occurred during the period of intoxication. In these instances, and even in black­outs, the drinker may remember more about events when reminded of them.) In the past, blackouts were thought to be relatively rare and were viewed as a strong indicator of alcoholism by many clinicians. However, it turns out that blackouts are far more common than previously thought and don't just occur in people with serious alcohol problems. Researchers are now beginning to look more closely at how and when blackouts occur, and there appear to be some disturbing trends. First of all, blackouts appear to be quite frequent among college students, with as many as 40 percent reporting them. But it's not just the memory loss that's disturbing--it's what happens during the periods for which no new memories are made. In one survey, students reported that after a night of heavy drinking they later learned about sexual activity, fights with friends, and driving, for which they had no memory at all. So it seems that blackouts may well be a serious health risk over and above the direct effects that alcohol has on the brain. Sadly, many people joke about blackouts as an embarrassingly funny result of heavy drinking. But they are no joke. Think about it this way: anything that impairs brain function enough to interrupt memory formation is very danger­ous. If it were a blow to the head, exposure to a toxic chemical, or a buildup of pressure in the brain that caused the blackout, it would be taken very seriously. Alcohol-induced blackouts should be taken seriously as well. Short of blackouts, though, it is also clear that alcohol impairs the ability to form new memories even after relatively low doses. Therefore, having a couple of beers while studying for an exam or pre­paring for a presentation at work is probably not a good strategy. The alcohol may promote relaxation, but it will also compromise learning and memory.

Hangover

One of the best-known symptoms of a hangover is a pounding head­ache. The cause is not exactly clear, but it is probably related to the effects of alcohol on blood vessels and fluid balances in the body. In any case, it is much easier to prevent the onset of pain than it is to relieve the pain once it has started. Therefore, the sooner a pain reliever is taken, the better. Some people take one before going to bed after a night of drinking. This way the chemicals in the pain reliever can prevent the pain signals in the brain from getting started as the alcohol is elimi­nated from the body. However, Tylenol (acetaminophen) should not be taken to treat a hangover because it can interact in a very dangerous way with alcohol and its by-products and damage the liver in some peo­ple. Aspirin or ibuprofen can be used instead, but both of these drugs can irritate the stomach and small intestine and together with alcohol may cause gastric upset.
The upset stomach and nausea associated with a hangover are harder to deal with. These may be caused by the toxic by-products of alcohol elimi­nation, irritation to the stomach, or both. No medicines treat these effects specifically. Rather, the best strategy is to eat foods that are gentle on the stomach and to drink plenty of fluids. Morning coffee may help to start the day after a night on the town, but its irritating effects on the stomach may make it an unpleasant waking. And because caffeine is a diuretic, it may also contribute to the dehydration that often accompanies alcohol drinking.

CYNTHİA KUHN