Neurodevelopmental Study of the Effects of Oral Ammonium Perchlorate Exposure on the Motor Activity of Pre-Weanling Rat Pups

摘要

The objective was to assess the neurotoxicity of ammonium perchlorate as it relates to the development of the motor system. Ammonium perchlorate is used in solid rocket propellant systems, and has been found in ground water at sites where this propellant is manufactured and stored. It readily dissociates in water and produces perchlorate ion that displaces the iodide (I-) anion and disrupts thyroid activity. The thyroid becomes underactive (hypothyroidism), leading to reduced levels of thyroid hormones triiodothyronine (T3) and thyroxine (T4). There is some evidence to suggest thyroid hormones play an important role in normal brain development, including areas of the brain related to motor activity. Thus, a neurobehavioral test for spontaneous locomotor activity was employed to detect developmental abnormalities within the brain systems mated to gross motor movement. Female rats were treated for two weeks prior to gestation through post-natal day (PND) 10 with one of 5 doses of ammonium perchlorate in their drinking water (0, 0.1,1.0, 3.0, or 10.0 mg.kglday). One male and female rat pup were randomly selected from each litter for testing of general locomotor activity at three preweanling ages - PNDs 14, 18, and 22. Pups were individually tested in automated Opto-Varimex Activity boxes where 9 different measures of activity were recorded for 90 consecutive minutes on each test day. Data was divided into 9,10-minute blocks, and was analyzed separately for each of the 9 dependent variables using a repeated measures ANOVA. The main effect for drug dose was not significant for any of the 9 measures, and there were no reliable interactions for treatment. Statistically reliable results were found for expected effects, such as changes in overall activity at different ages, and reduced activity from the start of a given test session to the end of the session.