Neurobehavioral assessment of mice following repeated oral exposures to domoic acid during prenatal development

Abstract

Domoic acid (DA) is an algal toxin which has been associated with significant neurotoxicity in humans, non-human primates, rodents, and marine mammals. Developmental exposure to DA is believed to result in neurotoxicity that may persist into adulthood. DA is produced by harmful algal blooms of Pseudo-nitzschia, raising concerns about the consumption of contaminated seafood. We evaluated oral exposures to DA during pregnancy in mice. Doses of 0 (vehicle), 1 or 3mg/kg/d of DA were administered by gavage to C57BL/6J mice on gestational days 10 to 17. The offspring were tested for persistent neurobehavioral consequences during early development, adolescence and adulthood. Neurobehavioral tests revealed both dose- and gender-related differences in several neurobehavioral measures, including motor coordination in the rotarod test, behavior in the elevated plus maze, circadian patterns of activity in Phenotyper cages, gait as assessed in the Catwalk, and exploratory activity in the Morris water maze. This study demonstrated significant gender-specific and persistent neurobehavioral effects of repeated prenatal oral exposures to DA at low-dose levels that did not induce toxicity in dams.