Developmental exposure to methimazole increases anxiety behavior in zebrafish

Behav Neurosci. 2015 Oct;129(5):634-42. doi: 10.1037/bne0000087. Epub 2015 Jul 27.

Abstract

The role of thyroid hormones in vertebrate development has been well documented for several decades. As hypothyroidism during critical periods of development can cause defects to the development of every major organ system, including brain, eye, and general morphology, we hypothesized that hypothyroidism would affect specific behaviors. To assess this, we treated zebrafish with the hypothyroid drug methimazole (MMI) and examined changes in anxiety, shoaling, vision, and locomotion. Following low-dose MMI exposure for the first 10 days of life, a time of rapid and significant development, larvae were removed from treatment and allowed to develop until 1 month of age. Comparisons between treated and controls took place between 10 and 30 days postfertilization to examine times both during and after treatment. Using the novel tank and startle response tests, we found that anxiety behaviors are significantly increased following MMI treatment. These effects persisted for several days following removal from treatment and indicate a prolonged effect of early hypothyroidism. However, permanent MMI effects on anxiety were not observed, as anxiety behaviors of early treated zebrafish recovered to control levels following 10 days out of treatment. In contrast to the strong link between MMI treatment and anxiety, shoaling and visual behaviors were not significantly affected within our experimental parameters. This indicates that disruption of thyroid system functioning early in life can differentially affect behavior by specifically altering anxiety responses without producing indiscriminate changes to overall behavioral development.

MeSH terms

  • Animals
  • Antithyroid Agents / toxicity
  • Anxiety / chemically induced*
  • Behavior, Animal / drug effects*
  • Case-Control Studies
  • Embryo, Nonmammalian / drug effects
  • Hypothyroidism / chemically induced
  • Hypothyroidism / psychology
  • Methimazole / toxicity*
  • Thyroid Gland / drug effects
  • Zebrafish

Substances

  • Antithyroid Agents
  • Methimazole