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At Rush Presbyterian-St. Luke's Medical Center in Chicago studied 21-day-old rat pups who were exposed to Ecstasy during a period corresponding to the first trimester in human pregnancy.
Dr. Jack W. Lipton and colleagues injected eight pregnant rats twice daily with MDMA from day 14 through day 20 of pregnancy, a period corresponding to the first three months of human fetal development. The scientists injected saline twice daily during the same period to another eight pregnant rats.
The researchers then examined the brain tissue of the rat pups when they were 21 days old, which is equivalent to a two- to six-year-old child.
"Our most striking finding was that 21-day-old ecstasy-exposed pups had a 502-percent increase in the number of dopamine neuron fibers in the frontal cortex compared with control animals," said Dr. Lipton. "Abnormal or overly numerous connections in the frontal cortex may result in aberrant signaling there, possibly resulting in abnormal behavior.
"Dopamine is a brain chemical that carries or transmits messages between nerve cells. It is involved in a variety of motivated behaviors, such as eating, sex, and drug-taking. The frontal cortex is important in planning, impulse control, and attention."
They also saw similar but smaller increases in dopamine fibers in the striatum (a brain area involved in locomotion and reward) and the nucleus accumbens (the primary site of action of rewarding stimuli), according to the report.
"Ecstasy-exposed pups also showed modest decreases in dopamine metabolism in brain structures that play key roles in reward, addiction, learning, and movement. There also was a reduction in serotonin metabolism. Serotonin also is a brain chemical that helps to regulate mood, sleep, and appetite," Lipton reported. "Interestingly, the reductions in dopamine and serotonin metabolism that were observed in the nucleus accumbens were evident in male, but not female, pups suggesting sex differences in vulnerability to some of Ecstasy's prenatal effects."
The rat pups also exhibited behavioral changes. "When the Ecstasy-exposed pups were placed in a new environment away from their littermates, they spent significantly more time exploring, signifying they did not adjust as easily to the new environment as the control animals," the authors said.
"Our findings show that exposing rats to Ecstasy at a time of prenatal development that correlates with the first trimester in humans may result in lasting changes in brain chemistry and behavior," said Dr. Lipton. "Our findings also suggest that MDMA exposure may result in hyperactivity or deficits in attention or learning. Further research is needed to learn more about the effects of prenatal exposure to this drug."
Source: The study, funded in part by NIDA, was published August 25, 2003 in the online issue of the journal Neurotoxicology and Teratology.
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