Disruption of paired-associate learning in rat offspring perinatally exposed to dioxins

Masaki Kakeyama, Toshihiro Endo, Yan Zhang, Wataru Miyazaki, Chiharu Tohyama*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


The prevalence of cognitive abnormalities in children has partly been ascribed to environmental chemical exposure. Appropriate animal models and tools for evaluating higher brain function are required to examine this problem. A recently developed behavioral test in which rats learn six unique flavor-location pairs in a test arena was used to evaluate paired-associate learning, a hallmark of the higher cognitive function that is essential to language learning in humans. Pregnant Long-Evans rats were dosed by gavage with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) at a dose of 0, 200, or 800 ng/kg (referred as Control, TCDD-200, TCDD-800, TBDD-200, or TBDD-800, hereafter) on gestational day 15, and the offspring was tested during adulthood. Paired-associate learning was found to be impaired in the TCDD-200 and TBDD-200 groups, but not in either group exposed to 800 ng/kg, the observations of which were ensured by non-cued trials. As for the emotional aspect, during habituation, the TCDD-200 and TBDD-200 groups showed significantly longer latencies to enter the test arena from a start box than the Control, TCDD-800, and TBDD-800 groups, suggesting that the TCDD-200 and TBDD-200 groups manifested anxiety-like behavior. Thus, both the chlorinated dioxin and its brominated congener affected higher brain function to a similar extent in a nearly identical manner. Use of the behavioral test that can evaluate paired-associate learning in rats demonstrated that in utero and lactational exposure to not only TCDD but also TBDD perturbed higher brain function in rat offspring in a nonmonotonic manner.

Original languageEnglish
Pages (from-to)789-798
Number of pages10
JournalArchives of Toxicology
Issue number3
Publication statusPublished - 2014 Mar
Externally publishedYes


  • Behavior
  • Dioxin
  • Higher brain function
  • Neurotoxicity

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis


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