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.
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001143:Arousal / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D009026:Mortality; D009043:Motor Activity / Q000187:drug effects*; D009048:Motor Skills / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis; D012018:Reflex / Q000187:drug effects*
D012313:RNA; D003520:Cyclophosphamide; D004247:DNA