Age-related decrease of plasma testosterone in SAMP8 mice: Replacement improves age-related impairment of learning and memory

• Published in: Physiology & behavior 1995-04, Vol.57 (4), p.669-673
• Main Authors: Flood, James F., Farr, Susan A., Kaiser, Fran E., la Regina, Maria, Morley, John E.
• Format: Article
• Language: English
• Subjects: Aging; Aging - blood; Aging - psychology; Animals; Avoidance Learning - drug effects; Behavioral psychophysiology; Biological and medical sciences; Drug Implants; Fundamental and applied biological sciences. Psychology; Hormones; Hormones and behavior; Learning; Learning - drug effects; Learning - physiology; Male; Memory; Memory - drug effects; Memory - physiology; Mice; Mice, Inbred Strains; Orchiectomy; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Species Specificity; Testis - anatomy & histology; Testis - drug effects; Testosterone; Testosterone - blood; Testosterone - pharmacology
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/0031-9384(94)00318-1

Corticosterone increases with aging but pregnenolone, dehydroepiandrosterone, and testosterone decrease. The marked decrease in hormones that occurs with aging may contribute to the age-related deficit in learning and memory. Administration of these hormones after training was found to improve long-term memory processing in normal young mice. SAMP8 (P8) mice show an age-related loss of learning and memory for a variety of tasks whereas age-matched control mice of the closely related SAMR1 (R1) strain do not. In this study, we found an age-related decrease in serum testosterone levels of 71 % between P8 mice 4 and 12 months of age, but only a 26% decrease between RI mice of the same ages. The difference between the P8 mice was significant ( p < 0.01) and the difference between the R1 mice was not. The decrease in testosterone in 12-month-old P8 mice was not accompanied by gross morphological change in 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 not produce a deterioration in learning and memory, indicating that low levels of testosterone per se are not responsible for the impairment seen in 12-month-old P8 mice. This suggests that impaired cognitive functioning of the older P8 mice was due to an interaction of aging and reduced testosterone levels.