Under The Influence

Alcohol is still the top drug of choice for teenagers. Although there is much research on its deleterious physical implications, the full range of its consequences is not yet known. For instance, what is alcohol's effect on brain development during adolescence?
Jaime "Jim" L. Diaz-Granados, associate professor of psychology, neuroscience and biomedical studies, has been studying brain changes in adolescent mice exposed to alcohol with funding from a $452,000 National Institutes of Health grant. Although other groups are studying alcohol response differences within adolescent and adult populations, this unique research project investigates the possibility that an adolescent exposure can affect the adult response.
Until recently, the dogma has been that the human brain is fully developed by age 5. "Several studies in recent years, though, point to more plasticity in brain development than researchers first thought," says Diaz-Granados, director of Baylor's Neuroscience Program. For instance, we now understand that levels of serotonin and other neurotransmitters -- chemicals that modulate behavior, emotion and virtually every brain function -- change throughout the teenage years and into the early 20s, he says.
"There are very important developmental processes still going on in adolescence," he says. "When you impose a drug that gets into the brain and causes a reaction in the brain, it could change the course of development."
Furthermore, the age of the individual when he or she takes that first drink also is more relevant than once believed. Those who begin drinking before age 15 are four times more likely to develop alcohol problems at some time in their lives than those who take their first drink after age 20, according to survey results published in the Journal of Substance Abuse. Few researchers, however, have tried to determine the extent to which physical factors account for the link between early drinking and later abuse.
In his laboratory at Baylor, Diaz-Granados uses inbred mice -- as genetically identical as possible without being clones -- to help him differentiate between physical and social aspects of drinking. To increase the scientific precision of his work, he often uses two control groups: animals whose first alcohol exposure occurs in adolescence and those who are exposed twice but with both exposures occurring during adulthood. This helps to ensure that the changes he finds are due to developmental timing rather than pre-exposure. "Our protocols allow us to specify the moment in development in which they are exposed to alcohol and the amount of alcohol they get," he says.
His findings suggest that early exposure to alcohol may predispose humans to addiction for two reasons: It seems to lead to drinking greater quantities to achieve the desired effect (i.e., building up a tolerance); and it seems to reduce the impact of the usual aversive properties of alcohol -- such as the nausea associated with overindulgence -- that helps others avoid addiction.
The tolerance theory is based on an experiment he conducted in which mice that had been exposed to alcohol at an early age, then re-exposed as adults with an acute ethanol injection, recovered their balance on a stationary rod more quickly than those with no prior exposure or those who first experienced alcohol as adults. Such tolerance could lead to drinking greater amounts, he says.
In the aversion hypothesis, mice exposed to alcohol early are less likely to be deterred by the ill effects of a large dose of alcohol. In that experiment, a large dose of alcohol (equivalent to approximately 12 beers) is given to the mouse immediately after the mouse consumes a sweet saccharin solution. After one such experience, naïve adult mice will avoid the flavoring. However, adult mice with early alcohol exposure during adolescence showed very little aversion to the saccharin solution when it was presented to them again. Mice first exposed to alcohol as adolescents and then re-exposed as adults respond differently from adults who had their first alcohol exposure as adults and adults with no prior alcohol exposure. This clearly suggests, Diaz-Granados says, that early exposure to alcohol changes the course of adolescent brain development, which results in an adult brain that is more susceptible to the influence of alcohol.
As his research continues, Diaz-Granados will delve further into the timing of alcohol exposure and whether chronic or binge drinking have different effects on withdrawal symptoms such as seizures.
He was studying the hippocampus -- the part of the brain that governs learning and memory -- as an undergraduate at the University of Texas at Austin when he first became interested in alcohol research. His interest increased after coming across research that showed that prenatal alcohol exposure -- known as fetal alcohol syndrome -- causes cells to be lost in that region of the brain. "I got into alcohol research as a means of getting into the hippocampus. But then I got interested in the social aspect of alcohol use and the damage that alcohol does in society," he says.
According to the National Institute on Alcohol Abuse and Alcoholism, by the time youth reach eighth grade, nearly 50 percent have had at least one drink and more than 20 percent report having been drunk. 
Although alcohol, like other drugs of abuse, affects the brain's reward pathway, some people find drinking so physically aversive they never develop the habit. "Others, however, take their first drink of alcohol and they immediately desire it. My theory is, we can move the brain down that continuum [toward addiction] by exposing the developing brain to alcohol earlier on," he says.
Alcohol abuse is a complex problem, and every bit of scientific knowledge represents a step toward helping those afflicted by it, he says. "As a scientist, you learn to be patient with the process and always appreciative to be a part of it."