Testosterone supplementation restores vasopressin innervation in the senescent rat brain

The vasopressin (AVP) innervation in the male rat brain is decreased in senescence. This decrease is particularly pronounced in brain regions where AVP fiber density is dependent on plasma levels of sex steroids. Since plasma testosterone levels decrease progressively with age in the rat, the possibility of restoring central AVP innervation by peripheral testosterone supplementation was investigated by giving senescent (33 months) Brown-Norway rats subcutaneous implants of either empty or testosterone-filled silastic tubes for the period of 1 month. Plasma testosterone levels of testosterone-treated animals were restored to values which did not differ from those of young animals. The results show that the age-related decline in AVP fiber density can indeed be reversed by testosterone supplementation. In contrast, oxytocin innervation, which was previously shown not to be testosterone-dependent, was not restored. These results show for the first time restoration of a specific innervation pattern in the senescent rat brain mediated by peripheral hormones and indicate that a considerable plasticity is retained in the aging central nervous system.