Volume 13, Number 1 (June, 1998)
MERIT Awardee Examines Long-Term Effects Of Prenatal Cocaine Exposure in Rats
By Steven Stocker, NIDA NOTES Contributing Writer
NIDA MERIT (Method to Extend Research In Time) Award winner Dr. Sheldon Sparber, at the University of Minnesota Medical School in Minneapolis, studies the effects of prenatal drug exposure on the fetus and newborn and the effects that may continue into adulthood. His animal studies on opiates and opiate withdrawal have greatly influenced the treatment of opiate-addicted pregnant women in methadone maintenance programs and their newborns, and his current research on cocaine could prove to be just as important.
In the 1980s, Dr. Sparber's animal studies provided a new perspective on whether opiate-addicted women should be treated with methadone. Earlier research findings had suggested that methadone is dangerous to the fetus and probably should not be given to pregnant heroin addicts. However, Dr. Sparber's group showed that the toxic effects on the offspring demonstrated in the earlier studies were due to excessively high doses of methadone and the stress of sudden withdrawal from methadone. "Unlike with adults, severe sudden withdrawal can be deadly for fetuses and infants," explains Dr. Sparber. "This is true for both animals and humans. But if you maintain human pregnant mothers on low but adequate doses of methadone and provide the newborns with medications, if necessary, to allow them to go through slow, mild withdrawal, their prognosis can be quite good."
In his current research, Dr. Sparber is investigating the effects of prenatal cocaine exposure in chickens and rats. He has found that cocaine injected into chicken eggs interferes with the hatching of the chicks, probably by restricting blood flow to the embryos. He also has discovered that this effect could be blocked with a medication called ritanserin, which, according to Dr. Sparber, opens up the possibility of a treatment to prevent the adverse effects of prenatal cocaine exposure.
In his studies with rats, Dr. Sparber is finding that prenatal cocaine exposure causes only minimal effects on brain chemistry and behavior - until the rats reach middle age. When tested at age 10 months to a year, rats that were exposed to cocaine during the last trimester of pregnancy start to show serious learning and memory deficits. "If the data from our animal studies are real and can be generalized to humans exposed to cocaine in utero, it would mean that those people might start showing learning and memory deficits at about age 30 to 40 or perhaps later," says Dr. Sparber.
As part of the research funded by the MERIT Award, Dr. Sparber will be investigating whether cocaine's long-term effects can be prevented by altering the rearing environment of the infant rats or by treating the pregnant mothers with medications such as ritanserin. According to Dr. Sparber, the MERIT Award with its longer period of funding will allow him to take risks in his research that he might not be willing to take with a conventional grant. "The MERIT Award gives you the opportunity to do innovative work that you wouldn't normally doif you had a 3-year grant," says Dr. Sparber. He adds that many important discoveries in biomedicine are made through serendipity. "If you have your eyes open and don't have any preconceived notions about what you're going to see, you might come up with some very exciting observations."
Dr. Sparber has been funded continuously by NIDA since 1972.
Dr. Jerry Frankenheim of NIDA's Division of Basic Research describes Dr. Sparber as being "at the cutting edge of his field." He salutes Dr. Sparber's "willingness to tackle the truly relevant questions in psycho-pharmacology, no matter how tough."
Dr. Sparber is a professor of pharmacology, psychiatry, and psychology at the university. He has published more than 150 scientific papers and has edited two books.
Sparber, S.B.; Lichtblau, L.; and Kuwahara, M.D. Experimental separation of direct and indirect effects of drugs upon neurobehavioral development. In: N.A. Krasnegor, et al. (eds.), Advances in Behavioral Pharmacology. Volume V: Developmental Behavioral Pharmacology, Lawrence Erlbaum Associates, Inc., Hillsdale, N.J., pp. 225-263, 1986.
Zhang, X.; Schrott, L.M.; and Sparber, S.B. Evidence for a serotonin-mediated effect of cocaine causing vasoconstriction and herniated umbilici in chicken embryos. Pharmacology, Biochemistry, and Behavior, 59(3): 585-593, 1998.
NIDA NOTES - Volume 13, Number 1
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