Liquor bottle labels in the U.S. carry this warning: "According to theSurgeon-General, women should not drink alcoholic beveragesduring pregnancy because of the risk of birth defects."

Those defects, especially mental retardation, blight the lives of babiesborn to mothers who drank to excess during their fetuses' ninemonths in utero.

Neuroscientists don't know enough yet about the possible damagecaused to infants of mothers who took cocaine during pregnancy.

They are learning more about the developing brains of fetal ratsdosed with cocaine. "With the use of an animal model," saidneuropsychologist Jerrold Meyer, "we are studying the interactions ofcocaine with fetal brain tissue in ways that either cannot be done withhuman fetuses, or very difficult to do for practical and ethicalreasons."

Meyer, on the faculty at the University of Massachusetts in Amherst,is principal author of a paper in the June issue of the Journal ofPharmacology and Experimental Therapeutics. Its title:"Characterization and localization of [125]RTI-55-labeled cocainebinding sites in fetal and adult rat brain."

[125]RTI-55 is a radiolabeled chemical cousin of cocaine; it isconsiderably more potent than its narcotic analogue molecule. Meyerand his co-authors dose normal fetal rodents with this congener drugat day 20 of gestation, then use autoradiography to visualize itsuptake by receptors in various regions of the brain.

"This is the first work to begin to visualize where in the brain thesecocaine recognition sites are located," Meyer told BioWorld Today."Previous to this, we didn't have any good idea of their location."

Cocaine's preferred binding sites turn out to be in the striatum, acerebral area involved in learning, memory, motivation, motorcontrol and sensory processing. "This study," Meyer said,"demonstrated the presence of cocaine receptors in the fetal brain ofrats, and showed that cocaine can act directly on these receptors."

He added, "This may explain some of the neurobehavioral problems_ such as excessive irritability and later cognitive problems _ seenin human newborns exposed to cocaine during pregnancy."

That exposure, Meyer said, is most acute in urban hospitals of theU.S., "where the incidence of maternal cocaine abuse at some pointin pregnancy is probably at least 10 to 15 percent."

In ongoing research, as yet unpublished, he has found that "treatmentof pregnant female rats with cocaine leads to a transient, notpermanent, down-regulation of the dopamine transporter in thestriatum, which is an important brain area for dopamine action post-natal. We found it at 10 days in the offspring. Then it normalized by30 days."

He observed that "people working with cocaine-exposed humaninfants do find that some of them show a hyper-arousal or irritability.It's conceivable that that could be related to excessive dopamineactivity."

Besides dopamine, two other neurotransmitters, serotonin andnorepinephrine, have key shares in cocaine's actions on the brain.Recent research, Meyer observed, "strongly suggests that these threecocaine recognition sites are similar to those in adult brain."

Very high doses of cocaine during gestation, he went on, "canproduce, we think, some physical teratogenic effects. An increase infetal blood pressure and tachycardia [racing heartbeat] can lead toblood-vessel rupture, brain hemorrhage, or death of a developinglimb bud, for example.

"Such vascular accidents," he pointed out, "are relatively rare. Weare interested, rather, in the larger population that may have subtlerbrain abnormalities produced by lower doses of maternal cocaine. Inthis and subsequent work," he concluded, "what we are trying to do isidentify the nature of the effects that cocaine can cause, so thatphysicians _ people working with cocaine-exposed infants _ canhave a better idea of what neurological abnormalities to look for, andcan, hopefully, develop appropriate interventions."

The National Institute of Drug Abuse funds Meyer's work. Thatagency's director, Alan Leshner, welcomed his group's "trulysignificant finding that the fetal rat brain contains specific bindingsites for cocaine, because it establishes an important concept thatpreviously had only been hypothesized. Using this animal model,"Leshner added, "to further investigate the interactions of cocaine withthese sites in the brain, and their consequences, can yield importantinsights into the mechanisms by which cocaine may affect the healthand development of human newborns who are exposed to the drugduring pregnancy." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.