RADIATION-INDUCED COGNITIVE DYSFUNCTION - AN EXPERIMENTAL-MODEL IN THE OLD RAT

Purpose: To develop a model of radiation-induced behavioral dysfunctio n. Methods and Materials: A course of whole brain radiation therapy (3 0 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16- 27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two- way avoidance, a nd a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months p ostradiation therapy. Results: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation th erapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23 % vs. 55%, p less than or equal to 0.001) and two-way avoidance (18% v s. 40%, p less than or equal to 0.01). Seven months postradiation ther apy the reaction time was increased (press-lever avoidance, 11.20 s vs . 8.43 s, p less than or equal to 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compar ed with controls. Pathological examination did not demonstrate abnorma lities of the irradiated brains at the light microscopic level. Conclu sion: Behavioral dysfunction affecting mainly memory can be demonstrat ed following conventional radiation therapy in old rats. This model ca n be used to study the pathogenesis of radiation-induced cognitive cha nges.