Long-term parental methamphetamine exposure of mice influences behavior and hippocampal DNA methylation of the offspring

Yossef Itzhak, I. Ergui, Juan Young

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24 Citations (Scopus)

Abstract

The high rate of methamphetamine (METH) abuse among young adults and women of childbearing age makes it imperative to determine the long-term effects of METH exposure on the offspring. We hypothesized that parental METH exposure modulates offspring behavior by disrupting epigenetic programming of gene expression in the brain. To simulate the human pattern of drug use, male and female C57Bl/6J mice were exposed to escalating doses of METH or saline from adolescence through adulthood; following mating, females continue to receive drug or saline through gestational day 17. F1 METH male offspring showed enhanced response to cocaine-conditioned reward and hyperlocomotion. Both F1 METH male and female offspring had reduced response to conditioned fear. Cross-fostering experiments have shown that certain behavioral phenotypes were modulated by maternal care of either METH or saline dams. Analysis of offspring hippocampal DNA methylation showed differentially methylated regions as a result of both METH in utero exposure and maternal care. Our results suggest that behavioral phenotypes and epigenotypes of offspring that were exposed to METH in utero are vulnerable to (a) METH exposure during embryonic development, a period when wide epigenetic reprogramming occurs, and (b) postnatal maternal care.Molecular Psychiatry advance online publication, 18 February 2014; doi:10.1038/mp.2014.7.

Original languageEnglish
JournalMolecular Psychiatry
DOIs
StateAccepted/In press - Feb 18 2014

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Methamphetamine
DNA Methylation
Epigenomics
Mothers
Postnatal Care
Phenotype
Maternal Exposure
Foster Home Care
Reward
Cocaine
Pharmaceutical Preparations
Fear
Embryonic Development
Psychiatry
Publications
Young Adult
Gene Expression

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Molecular Biology

Cite this

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abstract = "The high rate of methamphetamine (METH) abuse among young adults and women of childbearing age makes it imperative to determine the long-term effects of METH exposure on the offspring. We hypothesized that parental METH exposure modulates offspring behavior by disrupting epigenetic programming of gene expression in the brain. To simulate the human pattern of drug use, male and female C57Bl/6J mice were exposed to escalating doses of METH or saline from adolescence through adulthood; following mating, females continue to receive drug or saline through gestational day 17. F1 METH male offspring showed enhanced response to cocaine-conditioned reward and hyperlocomotion. Both F1 METH male and female offspring had reduced response to conditioned fear. Cross-fostering experiments have shown that certain behavioral phenotypes were modulated by maternal care of either METH or saline dams. Analysis of offspring hippocampal DNA methylation showed differentially methylated regions as a result of both METH in utero exposure and maternal care. Our results suggest that behavioral phenotypes and epigenotypes of offspring that were exposed to METH in utero are vulnerable to (a) METH exposure during embryonic development, a period when wide epigenetic reprogramming occurs, and (b) postnatal maternal care.Molecular Psychiatry advance online publication, 18 February 2014; doi:10.1038/mp.2014.7.",
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