Effects of Estradiol (-17beta) on learning, memory and cerebral energy metabolism in male rats after intracerebroventricular administration of streptozotocin.

Treatment of adult rats with intracerebroventricularly (i.c.v.) injected streptozotocin (STZ) may provide a relevant animal model of chronic neuronal dysfunction that is characterized by a decrease in both the neuronal metabolism of glucose and the formation of energy. The present study was designed to evaluate whether or not rats treated with triplicate i.c.v. STZ injection would show long-term effects in learning and memory behavior as measured by means of a holeboard test, closed field activity, and passive avoidance behavior over a period of 6 weeks. For this purpose, animals with good performance were discriminated from those with poor performance by the holeboard test before i.c.v. administration of STZ. After a 1-week training period with the holeboard all animals improved their abilities in learning and memory, and the improvement was maintained over the investigation period of 6 weeks in the control group. After i.c.v. STZ working memory (WM), reference memory (RM), as well passive avoidance (PA) behavior decreased, deteriorating progressively during the investigation period. The latter were accompanied by a permanent deficit in cerebral energy metabolism. The ongoing deterioration in behavior and the sustained deficit in cerebral energy metabolism occurring after a triplicate i.c.v. STZ administration lead us to assume that this animal model may be appropriate for the investigation of mechanisms characteristic for sporadic Alzheimer disease. In this context, the effect of Estradiol-17beta (E2) on behavior and energy metabolism was studied. We found that E2 slowed down the i.c.v. STZ-induced deterioration in memory functions, partially compensated the learning deficit, and improved the disturbances in cerebral energy metabolism to the extent that it was almost completely normal again. These findings underscore the beneficial effect of E2 in dementia disorders.