Young rats (26 days) were exposed to ionizing radiation of the head of 0, 1200, 2400, or 3000 rads total in 200 rads/day doses. The subsequent growth of irradiated rats was permanently impaired: such impairment was positively related to amount of irradiation. Beginning in adolescence, rats were trained on a horizontal/vertical visual discrimination in a runway task, and although all four groups mastered the discrimination, they differed in their patterns of acquisition. These results indicate long term effects are associated with a cranial irradiation regimen similar to that given to children suffering acute lymphocytic ieukemia (ALL).
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NSD is the nominal standard dose in rats, N is the number of fractions, and T is the elapsed time in days for Cr°+linear accelerator+betatron machines.) Large fractionated doses of cranial irradiation in humans (6000 rads) are clearly pathogenic , while the behavioral effects of the typical prophylactic doses (2400 rads) are uncertain [11, 23, 24, 33]. However, it is well known that behavioral and psychological disturbances can result even in the absence of identifiable brain pathology (e.g. [13,21]. There are numerous reports of behavioral deficits in animals resulting from exposures to ionizing radiation using single and fractionated doses to the head and whole body [14, 15, 21]. Overall, there has been a tendency to focus upon acute effects resulting in a paucity of data on the longer term effects of irradiation on behavior. Several acute studies in which fractionated doses of cranial radiation have been given to neonatal rats have reported behavioral sequelae of alternations in activity and aggression, exaggerated reactions to stressful stimuli, changes in avoidance behavior, and deficits in response alternation [3, 6, 29, 33, 38]. Neurological sequelae observed in these studies included hippocampal lesions with cell losses in the dentate nuclei. However, while these experiments constitute an important context, they are not directly relevant to an experimental model of the therapeutic treatments because "developmental ages" of the animals at irradiation (1-20 days during CNS cellular neurogenesis and myelinization ), time of testing (3--10 days later), dosages, and irradiated foci (cerebellum or hippocampus) were not comparable to those of children in the clinical setting. The purpose of the present study was to determine whether radiation to the central nervous system of rats had adverse effects upon later learning and performance when dosimetry and developmental age are comparable to that used in prophylactic treatment of the central nervous system in children suffering acute lymphocytic and myelogenous leukemia. The experiment incorporated in separate groups a range of doses of radiation that spanned the common therapeutic doses. Behavioral assays were of learning, tThis research was supported by grants to J. B. Overmier by NIMH (MH-13558), to W. Krivit by NCI (CA-21731), and by grants to the Center for Research in Human Learning (Minnesota) by NSF (BNS-03816) and NICHHD (HD-01136). M. E. Carroll was a NIDA postdoctoral fellow (DA-05068) during the conduct of this project. We thank J. Michael Flanigan, Robert D. Koppes and Stephanie J. Reynolds for their technical assistance.