Key neural system at risk from fetal alcohol exposure

In a study of adult monkeys who were exposed to moderate amounts of alcohol in utero, scientists have found that prenatal exposure to alcohol – even in small doses – has pronounced effects on the development and function later in life of the brain’s dopamine system, a critical component of the central nervous system that regulates many regions of the brain.

Writing in the current issue (Sept. 15, 2005) of the journal Alcoholism: Clinical and Experimental Research, a team of researchers led by Mary L. Schneider, a UW–Madison professor of occupational therapy and psychology, reports that when a monkey exposes her fetus to alcohol by drinking, the dopamine system of her offspring is altered. Effects on that key neural system, according to the study’s results, can manifest themselves up to five years after birth, when the monkeys are fully grown.

The influence of alcohol on the dopamine system, depending on the timing of exposure during gestation, varies, says Schneider, but illustrates yet another biological consequence of drinking while pregnant.

“It appears that there is no safe time to drink,” says the Wisconsin researcher. “And because our study looked at the effects of lower doses of alcohol than most previous studies, the results suggest there is no safe amount of alcohol that can be consumed during pregnancy. Even moderate drinking can have effects that persist to adulthood.”

The new study, conducted at UW–Madison’s Harlow Center for Biological Psychology, looked at the effects of moderate drinking on the offspring of three groups of pregnant rhesus macaques, each of which were provided access to moderate amounts of alcohol during various stages of gestation. In addition, there was a control group not exposed to alcohol.

Working with UW–Madison professor of medical physics Onofre DeJesus, Schneider’s group used PET scans to assess the function of the dopamine system of the adult monkeys exposed to alcohol in utero.

Dopamine is a key chemical messenger in the brain, helping it perform an array of functions ranging from simple movement to cognition to facilitating feelings of enjoyment and motivation. Perhaps the best-known dopamine-related pathology is Parkinson’s disease, caused by the death of the brain cells that normally secrete the chemical. But abnormalities in the functioning of the system can also contribute to such things as addiction, issues of memory, attention and problem solving, and more pronounced conditions such as schizophrenia.

In the new study, Schneider’s group used positron emission tomography or PET on the now-grown monkeys to evaluate the interplay of dopamine receptors and enzymes at work in the system. Schneider and her colleagues were able to see the chemical interplay in the brains of the monkeys exposed to alcohol in utero, and detected a range of effects, especially in the striatum, a region of the brain associated with cognition and other key functions.

“We’re seeing receptors and enzymes that are important in producing dopamine, and what was surprising to us was that dopamine was altered in opposite directions” depending on when during gestation the monkey’s developing brain was exposed to alcohol.

For two groups of monkeys, those exposed during early gestation, when dopamine neurons are first forming in the brain, and those exposed continuously throughout pregnancy, the dopamine system appears to be blunted, Schneider says. “If the dopamine system is blunted, you might not get the usual flushes of dopamine in response toe environmental events, and you may seek alcohol or drugs” as a substitute for the stimulation dopamine normally provides.

For the monkeys exposed to alcohol during middle-to-late gestation, the effect was the opposite: “Animals exposed later had supersensitive (dopamine) receptors. If you have supersensitive receptors, you’re more susceptible to sensory overload and environmental stimuli can become overwhelming.”

The new results add to a long list of alcohol’s negative effects on the developing fetus. In the last 30 years, scientists have come to understand that exposing the fetus to alcohol, the drug most widely abused by pregnant women, leads to a host of health and development issues, including low birth weight, facial deformities and mental retardation. The availability of powerful imaging techniques such as PET, which can illustrate the brain at work, are helping scientists make even finer distinctions, linking damage to the developing brain to behavioral problems and learning disabilities later in life.

“This is a big problem,” says Schneider. “People have been drinking since Biblical times, but it’s only been within the last few decades that we’ve begun to understand the effects of drinking on fetal health. The term ‘fetal alcohol syndrome’ wasn’t even coined until 1973.”

Studies of the effects of moderate drinking, says Schneider, are even more recent. The monkeys in her study consumed the equivalent of just one or two drinks a day.

“The blood alcohol content is about .04 or .05. If they were people, they could still drive, but the unseen effects have significant consequences. The take home message from this study is that there is no safe time to drink, even before pregnancy is detected.”

The new Wisconsin study was supported by a grant from the National Institute of Alcoholism and Alcohol Abuse.