Of Mice and
public-health concerns, University of Chicago researchers are working
to provide more concrete information on how pregnant mothers' use
of the drug methamphetamine may affect their newborns.
Alfred Heller, PhD'56, MD'60, professor in pharmacological & physiological
sciences, and Lisa A. Won, AB'79, PhD'87, research associate in
pharmacological & physiological sciences, are entering the second
year of a five-year grant from the National Institute on Drug Abuse
to study the consequences of maternal use of this harmful drug.
"meth," "crank," or "ice" depending on its form-can be easily made
from a mix of over-the-counter cold medicines and common industrial
chemicals. Its euphoric rush, with cocaine-like addictive properties,
stimulates the central nervous system for up to 24 hours. Though
prenatal drug exposure is already known to result in developmental
problems, a University of Colorado study found that pregnant meth
users comprise one of the most uninformed groups of drug users.
NIDA grant, Heller is using a unique tissue-culture system to study
the effects of meth on minute clusters of fetal mouse neurons. Pioneered
by U of C faculty members Aron A. Moscona and the late Beatrice
Garber, SM'48, PhD'51, these three-dimensional neuron clusters,
called aggregates, establish the connections, neurochemistry, and
electrophysiology of normal neurons found in the developing brain.
aggregates can live for up to a year, Heller and his team can monitor
drug-induced effects during the entire developmental history of
neurons, from the fetal to the adult stage.
gives us a tremendous amount of power to pinpoint where we should
go look in the intact animal," Heller explains. "This is a way to
look at the cells that we know are susceptible to meth-the dopamine
cells-and monitor them for various kinds of defects and sensitivities."
results from fetal-cell cultures have already begun to explain the
problems that may be faced by meth-affected babies.
Won and Heller
treated the cultures with the drug for varying periods of time and
then let them grow. The meth-treated cultures' levels of dopamine
and serotonin fell dramatically. When methamphetamine was removed
from the cultures, the cells resumed normal development, but the
cells never attained a normal level of those neurotransmitters.
researchers because an initial deficit in dopamine-known to be essential
to the development of locomotor function-could result in hyperactivity
and hypersensitivity. Some children born to mothers who have abused
meth, Heller notes, have shown this type of behavior.
a time out," Heller says. "The critical period is early in development-if
you don't have dopamine in this period of time, you can get a hyperactive
in the first phase of its NIDA grant work that a significant amount
of meth does cross from a mother's placenta to her fetus, the team
plans to collaborate with U of C pharmacologist Lewis Seiden, AB'56,
SM'58, PhD'62, to investigate the behavioral consequences of fetal
exposure to meth.
pregnant mice to the drug, the team will examine the neurologic,
cognitive, and behavioral status of the animals to assess the neurotoxic
risk of fetal exposure to methamphetamine.
"We and others
believe this is far from a trivial issue," Heller cautions, "and
may in fact be a major hidden public-health problem."-M.D.B.