AGE-RELATED DECREASE OF PLASMA TESTOSTERONE IN SAMP8 MICE - REPLACEMENT IMPROVES AGE-RELATED IMPAIRMENT OF LEARNING AND MEMORY

Corticosterone increases with aging but pregnenolone, dehydroepiandros terone, and testosterone decrease. The marked decrease in hormones tha t occurs with aging may contribute to the age-related deficit in learn ing and memory. Administration of these hormones after training was fo und to improve long-term memory processing in normal young mice. SAMP8 (P8) mice show an age-related loss of learning and memory for a varie ty of tasks whereas age-matched control mice of the closely related SA MR1 (RI) strain do not. In this study, we found an age-related decreas e in serum testosterone levels of 71% between P8 mice 4 and 12 months of age, but only a 26% decrease between R1 mice of the same ages. The difference between the P8 mice was significant (p < 0.01) and the diff erence between the R1 mice was not. The decrease in testosterone in 12 -month-old P8 mice was not accompanied by gross morphological change i n the testes. A SC testosterone implant, sufficient to increase plasma testosterone levels to 414 +/- 25 ng/dl, alleviated impaired learning and memory of a foot shock avoidance task in P8 mice. Castration of 4 -month-old P8 mice did wt produce a deterioration in learning and memo ry, indicating that low levels of testosterone per se are nor responsi ble for the impairment seen in 12-month-old P8 mice. This suggests tha t impaired cognitive functioning of the older P8 mice was due to an in teraction of aging and reduced testosterone levels.