Key Neural System At Risk From Fetal Alcohol Exposure

Writing in the current issue (Sept. 15, 2005) of the journalAlcoholism: Clinical and Experimental Research, a team of researchersled by Mary L. Schneider, a University of Wisconsin-Madison professorof occupational therapy and psychology, reports that when a monkeyexposes her fetus to alcohol by drinking, the dopamine system of heroffspring is altered. Effects on that key neural system, according tothe study's results, can manifest themselves up to five years afterbirth, when the monkeys are fully grown.

The influence of alcohol on the dopamine system, depending on thetiming of exposure during gestation, varies, says Schneider, butillustrates yet another biological consequence of drinking whilepregnant.

"It appears that there is no safe time to drink," says the Wisconsinresearcher. "And because our study looked at the effects of lower dosesof alcohol than most previous studies, the results suggest there is nosafe amount of alcohol that can be consumed during pregnancy. Evenmoderate drinking can have effects that persist to adulthood."

The new study, conducted at UW-Madison's Harlow Center for BiologicalPsychology, looked at the effects of moderate drinking on the offspringof three groups of pregnant rhesus macaques, each of which wereprovided access to moderate amounts of alcohol during various stages ofgestation. In addition, there was a control group not exposed toalcohol.

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

Dopamine is a key chemical messenger in the brain, helping it performan array of functions ranging from simple movement to cognition tofacilitating feelings of enjoyment and motivation. Perhaps thebest-known dopamine-related pathology is Parkinson's disease, caused bythe death of the brain cells that normally secrete the chemical. Butabnormalities in the functioning of the system can also contribute tosuch things as addiction, issues of memory, attention and problemsolving, and more pronounced conditions such as schizophrenia.

In the new study, Schneider's group used positron emission tomographyor PET on the now-grown monkeys to evaluate the interplay of dopaminereceptors and enzymes at work in the system. Schneider and hercolleagues were able to see the chemical interplay in the brains of themonkeys exposed to alcohol in utero, and detected a range of effects,especially in the striatum, a region of the brain associated withcognition and other key functions.

"We're seeing receptors and enzymes that are important in producingdopamine, and what was surprising to us was that dopamine was alteredin opposite directions" depending on when during gestation the monkey'sdeveloping brain was exposed to alcohol.

For two groups of monkeys, those exposed during early gestation, whendopamine neurons are first forming in the brain, and those exposedcontinuously throughout pregnancy, the dopamine system appears to beblunted, Schneider says. "If the dopamine system is blunted, you mightnot get the usual flushes of dopamine in response toe environmentalevents, and you may seek alcohol or drugs" as a substitute for thestimulation dopamine normally provides.

For the monkeys exposed to alcohol during middle-to-late gestation, theeffect was the opposite: "Animals exposed later had supersensitive(dopamine) receptors. If you have supersensitive receptors, you're moresusceptible to sensory overload and environmental stimuli can becomeoverwhelming."

The new results add to a long list of alcohol's negative effects on thedeveloping fetus. In the last 30 years, scientists have come tounderstand that exposing the fetus to alcohol, the drug most widelyabused by pregnant women, leads to a host of health and developmentissues, including low birth weight, facial deformities and mentalretardation. The availability of powerful imaging techniques such asPET, which can illustrate the brain at work, are helping scientistsmake even finer distinctions, linking damage to the developing brain tobehavioral problems and learning disabilities later in life.

"This is a big problem," says Schneider. "People have been drinkingsince Biblical times, but it's only been within the last few decadesthat 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 equivalentof 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 significantconsequences. The take home message from this study is that there is nosafe 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.