Sep. 2, 2003 Researchers at Rush Presbyterian-St. Luke's Medical Center in Chicago have shown that 21-day-old rat pups exposed in the womb to the drug MDMA (3,4-methylenedioxymethamphetamine, often called Ecstasy) during a period corresponding to the first trimester in human pregnancy exhibit changes in brain chemistry and behavior.
"Existing data suggest that most women who use MDMA stop taking it when they learn they are pregnant," says NIDA Director Dr. Nora D. Volkow. "But the animal studies that linked this drug to neurobiological changes and learning impairments were conducted in situations analogous to the third trimester in humans. This study sought to investigate a more true-to-life situation by looking at the consequences of Ecstasy exposure early in pregnancy."
The study, funded in part by NIDA, was published August 29 on the journal of Neurotoxicology and Teratology Web site.
Dr. Jack W. Lipton, doctoral student James Koprich, and their colleagues injected 8 pregnant rats twice daily with MDMA from day 14 through day 20 of pregnancy, a period corresponding to the first 3 months of human fetal development. The scientists injected saline twice daily during the same period to another 8 pregnant rats. The researchers examined brain tissue of the rat pups when they were 21 days old. A 21-day-old rat pup is roughly equivalent to a 2- to 6-year-old child.
"Our most striking finding was that 21-day-old MDMA-exposed pups had a 502-percent increase in the number of dopamine neuron fibers in the frontal cortex compared with control animals," notes 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.
The scientists 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).
MDMA-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. 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 MDMA'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.
"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," notes 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."
The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and information on NIDA research and other activities can be found on the NIDA home page at http://www.drugabuse.gov
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