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

Physiol Behav. 1995 Apr;57(4):669-73. doi: 10.1016/0031-9384(94)00318-1.

Abstract

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 R1 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / blood*
  • Aging / psychology*
  • Animals
  • Avoidance Learning / drug effects
  • Drug Implants
  • Learning / drug effects
  • Learning / physiology*
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Mice
  • Mice, Inbred Strains
  • Orchiectomy
  • Species Specificity
  • Testis / anatomy & histology
  • Testis / drug effects
  • Testosterone / blood*
  • Testosterone / pharmacology*

Substances

  • Drug Implants
  • Testosterone