The newsletter of the Memory Disorders Project at Rutgers University

Mr. P is starting to stagger. He's imbibed enough grain alcohol to meet the official standard for binge drinking: five or more drinks in a row. It means drinking like college students on spring break: not to enjoy the beverage, but to become intoxicated. Under the watchful but nonjudgmental gaze of scientists in the laboratory headed by Fulton T. Crews, Ph.D., at the University of North Carolina, Chapel Hill, Mr. P wobbles around a bit more, takes another nip from the bottle, and then curls up to nap in a drunken stupor.

Unlike students on a spring-break bacchanalia, Mr. P is chugging his booze for science. Crews and his colleagues study the long-term effects of excessive drinking on the brain. After Mr. P endures a sufficient number of binges, Crews will remove Mr. P's brain, slice it up, and scrutinize the neurons for damage.

Don't call in the SWAT team just yet. Mr. P is not a human, but a special "alcohol preferring" laboratory rat, or "P rat," bred over many generations to prefer alcohol to water. "It's hard to get rats to drink," Crews notes. "They don't like the taste." With continued drinking, P rats become tolerant to the effects of alcohol and need more and more to get inebriated. Over time, P rats become dependent, just like humans.

Experiments by Crews using P rats and their teetotaler equivalent, the alcohol nonpreferring, or "NP," rat, have revealed that alcohol abuse disrupts brain function in multiple ways-even on the level of gene activity. Binge drinking is particularly toxic, especially in adolescents. And the rat experiments suggest that alcohol-related brain changes persist weeks or even years after the rats-and presumably people, too-go on the wagon. In hardcore alcoholics who drink to intoxication virtually every day, the damage may be permanent. But even in heavy social drinkers, alcohol may do measurable damage. The good news is that after a long-enough period of sobriety, the brain can substantially recover.

Of Mice and Men

That hardcore alcohol abuse harms the brain is not news to scientists. "In human alcoholics, the brain is smaller, and when they stop drinking the brain starts to grow back," Crews explains. But the mere observation that alcoholics have shrunken brains doesn't prove that heavy drinking is the sole cause. "You could also say that alcoholics don't eat as well, or they already had a smaller brain and that the small brain caused them to become alcoholics, or you could say it's because a lot of alcoholics smoke," Crews explains. The P and NP rats have allowed Crews to focus narrowly on the effect of alcohol. All other factors being the same-diet, health, genes, stress levels-if a rat drinks alcohol, what happens to its brain?

More importantly, how do alcohol-induced changes to the brain contribute to the development of the complex disease we call alcoholism? To be sure, P rats are not merely pint-sized alcoholics with four feet, whiskers, and a curly tail. Alcoholism is a complex disease involving many factors besides just excessive drinking. Exposure to drinking behavior in the family, genetics, and socio-economic factors all influence whether a person becomes an alcoholic. However, the rats allow scientists to investigate alcohol's specific effects on the brain, which will hopefully elucidate the process that leads to alcohol addiction.

Levels of Abuse

Scientists at the National Institute of Alcohol Abuse and Alcoholism estimate that more than 17 million Americans, or 8.5% of the population, are either full-blown alcoholics or abuse alcohol. At the top of the scale are those whose drinking has reached the level of a physical dependence or addiction. If they stop drinking, they experience physical symptoms of withdrawal, like insomnia, anxiety, tension, and uncomfortable body sensations that drive them back to the bottle.

Moreover, alcohol use disrupts their lives. "It costs them productivity at their jobs and problems with relationships, but yet they persist in drinking despite these negative consequences," says neuropsychologist H. Scott Swartzwelder, Ph.D., a senior research career scientist at the VA Medical Center in Durham, North Carolina. The legions of people who drink regularly-and sometimes heavily-but have never experienced withdrawal symptoms, lost their jobs, or suffered a health or personal crisis due to drinking may look at the foregoing description and think, "I'm no alcoholic." That may be so, but heavy social drinkers can still suffer brain effects without realizing it. "Alcoholic has actually become a bit of a dirty word these days," Swartzwelder explains. "We talk more now about alcohol use disorders."

So who are these disordered alcohol users? Let's arbitrarily define a heavy social drinker as someone who has two to three drinks on weeknights and binges on weekends. "These people have never been diagnosed with an alcohol use disorder or sought treatment, but you do find that they suffer long-term cognitive deficits," Swartzwelder says. "They are of the same kind, but not the same degree, as you see in hardcore alcoholics."

The types of mental problems caused by heavy drinking are well documented. A recent study Swartzwelder conducted at the VA with colleagues Sandra Zinn and Roy Stein focused on 27 recovering male alcoholics. They had been dependent on alcohol for an average of 30 years, most of whom started drinking when they were teenagers. The number of drinks they consumed per week ranged from 2 to 46, with half drinking more than 13. The people in the study, none of whom were still drinking at the time, were given a battery of tests to measure their mental performance in comparison to a group of non-alcoholics of similar age. They performed significantly less well in abstract reasoning, working memory, learning new information, and the ability to plan and execute activities.

These deficits are noticeable in alcohol abusers, Swartzwelder explains. "They may not track well in conversation, may be easily distractible, and tend to be very concrete in the way they present their ideas. You can tell something's going on there." But in heavy social drinkers, similar problems are present, although more subtle. "You might notice as soon as you started to push that system a little bit, Swartzwelder explains. "If you put them in a situation where they have to learn a lot of new information, or they have to reason through a problem that demands abstract thinking." Imagine Joe, a manager who downs two or three martinis a night and may become somewhat inebriated on weekends at a party. He's been doing this since college, but never blacks out, loses his car, or stumbles glassy-eyed onto the sidewalk at bar time. How's his brain doing?

In ordinary conversation, bragging about his kids or recounting a recent vacation, he seems lucid and sharp. But in an important business meeting where he has to juggle a lot of information and make quick judgments, the cracks start to show. "Joe is going to seem fine at a party with his friends or having a conversation with his wife at night, but you put him in that demanding situation at work and his performance is going to decrease," Swartzwelder says.

The Insidious Slide

The journey to alcohol abuse is a gradual. For many, it starts with a 14-year-old and his friend taking a few experimental nips at Dad's scotch bottle. At age 18, the amount people drink commonly rises precipitously. Then it may become a daily or weekly routine, not just an occasional indulgence. Then people may start to cover up their drinking, or drink more at home. They begin to experience cravings for alcohol, and the amount of alcohol it takes to achieve that warm fuzzy glow increases.

They have trouble refusing that third round at the bar after work. Their work suffers, they fight about drinking with their spouses, and so on, until drinking may become necessary to get through the day. One of the great mysteries is why some people go down this path and others do not. Genetic disposition is thought to play a role, but Crews believes that the mounting effects on the brain of alcohol use also helps to explain the insidious slide.

Key hotspots of alcohol abuse, research suggests, are the frontal lobes of the brain. Just behind the eyeballs, the frontal lobes are central to the so-called executive functions of the mind, such as foresight, judgment, and execution of plans. The executive function of the brain is the invisible companion by your side that taps you on the shoulder and says, "Enough now, time to go home."

With increasing harm to the brain's executive functions, Crews believes, you are less able to control the impulse to drink. You are less able to take the negative consequences of heavy drinking into account when making decisions-like when to stop drinking. You are less capable of resolving to reduce your drinking and execute that plan. Your emotional control is also impaired, so drinking gets you into trouble as you make bad choices. The collective effect, Crews believes, is to reinforce the behaviors that lead to continued drinking-and continued brain damage. "My hypothesis is that the drug is changing the brain in a way that promotes more drug taking."

Reversing the Damage

This sounds pretty grim, but Crews' research with drunken rats also offers a hope of salvation. Although the effects of alcohol on the brain do linger, with sobriety or moderation the brain can recover. Within only a few weeks, the process that forms new brain cells starts to kick in. Some research suggests that after hardcore alcoholics achieve sobriety, healthy areas of the brain are recruited to take over the function of damaged areas. Exercise, good nutrition, and, above all, limiting alcohol consumption or total abstinence contribute to recovery.

How you drink appears to be very important to the amount of damage the brain suffers from alcohol. "When you load on a lot of alcohol at a time, what you are doing is jerking around the brain more," Swartzwelder explains. "You are sedating it more when you drink, and after the alcohol is metabolized, brain activity just doesn't come back to its baseline-it kind of overshoots. It is during that overshoot that the brain is most vulnerable. That's when you lose your cells."

Swartzwelder says that one of the most important insights emerging from research on alcohol's effect on the brain is that people who start drinking in adolescence are at higher risk of developing alcohol problems in adulthood. The adolescent brain is more vulnerable to damage but also more immune to some of the short-term intoxicating effects of alcohol. Alcohol use in adolescence, when the brain is still developing, may put a person on a trajectory toward alcohol dependence. "What happens when you put alcohol in there at that age?" Swartzwelder asks. "Maybe you are creating permanent aberrant wiring that might predispose that individual to abuse alcohol later or to use more later."

The bottom line is that preventing alcohol use and abuse in adolescence can make a huge impact on what happens later, Swartzwelder emphasizes. "Every year you can postpone the initiation of drinking, you decrease the likelihood that person will have alcohol problems for the rest of his life. If you can get them through middle school without drinking, you're great. If you can get them through high school without drinking, then you're really winning. If you can get them through college, then you're a god."


  • "Executive functioning early in abstainance from alcohol," by Sandra Zinn, Roy Stein, and H. Scott Swartzwelder. (Alcoholism: Clinical and Experimental Research, September 2004, Volume 28, Numbver 9, pp., 1338-1346.)
  • "Alcohol-induced neurodegeneration: where, when, and why?" by Fulton T. Crews and others. (Alcoholism: Clinical and Experimental Research, February 2004, Volume 28, Number 2, pp. 350-364.)
  • "Alcoholic Neurobiology: Changes In Dependence and Recovery," By Fulton T. Crews and others. (Alcoholism: Clinical and Experimental Research, August 2005, Volume 29, Number 8, pp. 1504-1513.)