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

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 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.