An animal model to detect learning deficits following treatment of the immature brain. Studies using radiation and methotrexate.

Learning deficits have been noted in children with acute leukemia given methotrexate (MTX) with and without cranial irradiation (RT) for prophylaxis. A rat model has been developed to assess treatment effects on learning. The test used was altered performance of a simultaneous discrimination task in a standard operant conditioning box, employing the mean number of days needed to score 80% correct responses as the criterion. An illustrative experiment distributed suckling rats among four groups: (1) 36 controls; (2) 14 cranial RT (1,000 R); (3) 14 MTX (5 mg/kg i.p.); (4) 36 RT + MTX 24 h later, and (5) 12 undernourished controls (to match poor weight gain patterns of treated animals). Survivors were tested 10-12 weeks later: values for groups 1-5 in order were 3.9, 4.1, 4.7, 5.0 and 4.0 days. Only group 4 results were significantly different from group 1 (p = less than 0.05).