A comparison of behavioral and anatomical measures of hydroxyurea induced abnormalities

Hydroxyurea, a drug which has antimitotic effects was administered once (150 mg/kg) to pregnant dams on the sixth, ninth, twelfth, fifteenth and eighteenth day of gestation. Litters of these dams plus control subjects were tested behaviorally from two days of age until sacrificed at 21 days of age. The following tests were conducted: (i) surface righting, (ii) mid‐air righting, (iii) cliff avoidance, (iv) swimming development, (v) pivoting and (vi) startle. In righting, cliff and startle a litter was tested until all members displayed a criterion response and that age provided the score for statistical analysis. In swimming and pivoting, time and frequency measures were analyzed. There were no significant treatment effects on any of the behavioral measures. Rat pups of dams injected on Day 9 of pregnancy evidenced hydrocephaly and micropthalmia. The latter observation was confirmed by eye weights which were significantly reduced in this group at 21 days of age. Regional brain weight measurements did not distinguish among the groups. Hydrocephaly was variably associated with necrotic brain tissue, loss in weight, behavioral delays and early death. The results suggested that the assertion of greater sensitivity of behavioral compared to morphological measures in screening for drug hazards needs to be qualified. A step wise procedure for screening was proposed and it was suggested that behavioral studies need to include assessments of brain pathology as a bridge between functional and structural approaches.