Behavioral measures used in the CBTS were negative geotaxis, olfactory discrimination, auditory startle habituation, 1‐hr and 23‐hr activity, an operant discrete trial discrimination task, and activity following amphetamine challenge. Body weights and certain physical landmarks of development also were monitored in two separate studies, one using prenatal treatment with 0, 0.5 or 2.0 mg/kg d‐amphetamine sulfate sc on gestation days 12‐15, the other using 0, 2.0 or 6.0 mg/kg methylmercuric chloride by gavage on gestational days 6‐9. An untreated control group also was included in each study. The CBTS design allowed evaluation of reproducibility and detection sensitivity of these methods, as well as the impact of early testing experience on later assessments, offspring sex differences in response levels and variability, and the contribution of litter‐to‐litter variation to behavioral measures used in this standardized protocol. Results obtained at the six participating laboratories are discussed in relation to each of these factors and to the degree of overt toxicity obtained with each compound. Behavioral data were reproducible, and detection sensitivities of the tests were very good, requiring no more than 5‐25% change from control values for either sex. Early testing experience was not found to be a major factor in determining later behavioral levels, but litter was found to contribute considerable variability to all physical and behavioral data.
In the first of two experiments, CD rat litters were used to characterize activity patterns obtained in a size-adjustable, single photodetector chamber. Beginning on postnatal Day 10 or 12, pups were tested repeatedly over clean bedding (C) or over bedding removed from each pup's home cage (HC). In C rats of both sexes and in HC females, short-term activity levels peaked on Day 16. However, HC males displayed an earlier and even greater elevation in activity from Day 12 to 16. This overall pattern was found in rats tested either every second or fourth day. In the second experiment, Long-Evans pups were assigned to each testing condition (C vs HC) and activity measured beginning on Day 12. Peak levels were seen in all Long-Evans rats on Day 16 and only females showed significant alterations as a function of bedding condition. When overall activity levels of the two strains were compared, significant differences were found on Days 12, 24, 30, and 120 in males, and 12, 24, and 30 in females. Significant differences between strains in activity as a function of bedding condition were found in males on Days 12, 20, 24, and 120 and in females on Days 12, 30, and 60. These data confirm the generality of a developmental hyperactivity phase in isolated juvenile rats. However, different patterns of hyperactivity were found in male vs female rats across strains. CD males were more active in the presence of HC olfactory cues, while in Long-Evans rats, female activity was affected more by bedding condition.
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