Effects of cyclophosphamide treatment of newborn mice on the development of swimming and reflex behavior and on adult behavioral performance

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Abstract
Cyclophosphamide (CP), an antineoplastic agent, was administered subcutaneously to Swiss‐Webster mice on the day of birth and the mice were later tested for developmental or adult behavioral abnormalities. The CP dosages of 20, 30, or 45 mg/kg of body weight retarded maturation of swimming ability and 45 mg/kg retarded maturation of the righting reflex. At 7 weeks of age mice treated neonatally with 30 or 45 mg/kg of CP had reduced locomotor activity and were more emotionally reactive than controls in an open field. Mice treated with 30 but not 20 mg/kg of CP tended to avoid shock less often than controls and those treated with 20 mg/kg fell more frequently when crossing a rotating rod for food. Rotorod performance was improved by treatment with 45 but not 30 mg/kg of CP. All dosages examined decreased body weight gains but only 30 or 45 mg/kg resulted in gross body malformations. The results indicate that CP can functionally impair the development of mice and that some of these impairments are independent of gross body malformations.