Researchers Find More Cause to Condemn Prenatal Exposure to Alcohol

by Carl Sherman

March 31, 2009

Prenatal exposure to alcohol can have devastating effects, including the severe intellectual and physical disabilities of fetal alcohol syndrome. But such exposure may lead to a different sort of trouble years later: Teenage children of mothers who drink might be at heightened risk of alcohol abuse themselves, suggest a series of studies.

At least some of this vulnerability is a matter of taste—or taste and smell, to be precise. Prenatal exposure, investigators say, appears to “tune” chemosensory processes to make alcohol more appealing. This preference persists into adolescence—a risky time when substance abuse often begins—and may shape social interactions at a time when peer influence is particularly strong. [See the Cerebrum article “The Teen Brain: Primed to Learn, Primed to Take Risks.”]

“We learn about the flavors of foods before we ever taste them,” says Julie Mennella, a biopsychologist at the Monell Chemical Senses Center in Philadelphia. “We learn through flavor cues in amniotic fluid and mother’s milk what foods the mother has access to and prefers.” Babies are more accepting of carrots if the mother ate carrots while pregnant, or of fruit if she ate fruit, for example.

The adaptive process is equally at work when the mother drinks alcohol, smokes tobacco or consumes other potentially harmful substances. “Those flavors are also transmitted,” Mennella says. Research in her lab showed that when they are 6 to 12 months old, babies of mothers who drank alcohol “mouth” toys scented with alcohol more than babies of nondrinkers.

Other researchers have been exploring the development of sensory preference and its implications for alcohol abuse in detail. “It’s a general phenomenon among mammals,” says Steven L. Youngentob, professor of neuroscience and physiology at State University of New York Upstate Medical University in Syracuse. Researchers in his laboratory found that when pregnant rats were fed a liquid diet that included what would correspond to a moderate human intake of alcohol (about two 5-ounce glasses of wine daily), their 15-day-old offspring drank significantly more ethanol, when given the chance, than infant rats whose mothers had consumed a liquid diet unspiked with alcohol. They have linked this increased avidity to both taste and smell. The research was published online March 9 by the Proceedings of the National Academy of Sciences.

Youngentob’s research team has  looked most closely, thus far, at odor, the strongest sense in rats. When prenatally exposed rats encounter ethanol, they sniff it significantly more than do control animals, an instinctive response that shows attention and attraction to the odor.

The researchers tracked the effects of maternal alcohol to the neurobiological level. They dissected the olfactory epithelium from the rats’ nasal passages and measured electrophysiological activity when these odor-sensitive cells were exposed to various chemicals. The response to ethanol was significantly stronger in tissue taken from prenatally exposed animals.

In rats, effects linger into adolescence

Although the enhanced behavioral and electrophysiological responses to alcohol disappeared by adulthood, they were still there when rats were tested in adolescence. A study by the Youngentob lab published Jan. 15 in the journal Behavioral and Brain Functions explored this critical period. The researchers divided prenatally exposed and unexposed rats into sex-matched sibling pairs. Beginning when they were 29 days old—adolescence for a rat—one member of each pair (the “demonstrator”) was given alcohol or water and reunited with its “observer” cagemate. The process was repeated for four days.

For 30 minutes after each exposure, the experimenters measured how much time each observer rat spent following its demonstrator—a social interaction guided by olfactory cues. Observers that had been prenatally exposed to alcohol followed intoxicated demonstrators significantly more than the control rats did. There was no difference in how much they followed water-fed rats.

If a similar pattern were to hold for human adolescents, “the potential take-home message is that exposure to alcohol before birth increases the propensity to interact with intoxicated individuals,” Youngentob says. Given that human adolescents often are highly susceptible to peer pressure, particularly in matters that involve risk and experimentation, the findings suggest that a history of fetal exposure might make it more likely for adolescents to fall in with questionable companions, worsening the risk of substance abuse and addiction.

The findings also describe the power of peer association. When the researchers tested the observer rats several days later, they found that a recent encounter with an intoxicated cagemate significantly increased the sniffing response to ethanol. And rats that had been doubly exposed—prenatally and at adolescence—showed the strongest response of all. “Mere interaction, the exposure to odor in a social setting, was enough to augment the fetal experience,” Youngentob says.

Whether re-exposure in adolescence prolongs the odor preference for alcohol into adulthood is not clear. In these studies, adult female rats that had been doubly exposed showed a heightened sniffing response, while male rats did not. But it may not matter, Youngentob says: “In the real world, adding adolescent alcohol exposure to fetal exposure opens Pandora’s box. The rest becomes a progressive pattern that can lead to abuse.”

Mennella calls the Youngentob lab work elegant and says that it complements her own: “As someone who does research with human infants, I appreciate animal-model research that can ask questions I can’t, and can control what happens from the time of fetal exposure.”

From birth onward, human behavior around alcohol and other drugs is influenced by a complex system of emotional experiences and environmental forces that shape beliefs and attitudes, Mennella says, and the thread of something as subtle as olfactory response is all but impossible to follow through this labyrinth. But putting human and animals research together allows for a deeper look into what processes underlie early experiences and later memory activation, she says. “If we want to devise better prevention programs, we need to understand what happens before drinking has even begun.”