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2.18.2014

Research Finds Long-Term Methamphetamine Exposure in Mice Affects Offspring

A study by three Miller School researchers has found that long-term methamphetamine exposure in mice affects the cognitive development, behavioral characteristics and epigenetics in the hippocampus of their offspring — possibly for generations.

The study, “Long-Term Parental Methamphetamine Exposure of Mice Influences Behavior and Hippocampal DNA Methylation of the Offspring,” authored by Yossef Itzhak, Ph.D., professor of psychiatry and behavioral sciences; Ian Ergui, an undergraduate student at the John P. Hussman Institute for Human Genomics; and Juan I. Young, Ph.D., assistant professor in the Dr. John T. Macdonald Foundation Department of Human Genetics, was published in the February 18 edition of the journal Molecular Psychiatry.

“Methamphetamine is currently a major drug of abuse, even surpassing cocaine because of its lengthy high,” says Itzhak, who was the lead author of the paper. “The majority of methamphetamine users are of reproductive age, and a large number of them do not stop abusing when they become pregnant. Much research was done in the 1980s and 1990s on cocaine babies, but almost no research has been conducted on methamphetamine-exposed babies. The goal of our study was to investigate the behavioral and epigenetic outcomes of parental methamphetamine exposure on the offspring.”

The researchers found that adult male offspring who had been exposed showed enhanced response to cocaine-conditioned reward and hyperlocomotion, suggesting higher vulnerability to cocaine than control counterparts. In addition, both male and female offspring had reduced response to conditioned fear, which is a test for long-term memory and suggests cognitive deficiencies. These behavioral manifestations were accompanied by alterations in DNA methylation in the hippocampus, suggesting that parental methamphetamine exposure induced “epigenetic reprograming” in the offspring’s brain cells. Cross-fostering experiments were conducted to investigate the influence of maternal care on the offspring. Results demonstrated that maternal care influences both behavioral effects on offspring and hippocampal DNA methylation. The hippocampus is a major brain region involved in cognition and emotional behavior.

“Our results suggest that negative behavioral and epigenetic traits in offspring are the result of exposure during both embryonic development and postnatal maternal care; future studies will investigate whether these phenotypes are transmitted to subsequent generations and elucidate mechanisms of transgenerational transmission,” said Itzhak.

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