Dose-Dependent Effects of Dihydrotestosterone on Place Learning and Brain Derived Neurotrophic Factor in Male Rats

The influence of androgens on spatial memory in humans is of particular concern with the high prevalence of age-related decline in spatial memory, prostatic cancer, and androgenic alopecia in our community. Rodent studies have demonstrated that a high dose of testosterone (T) improves spatial memory. However, they have not fully addressed the influence of androgens on spatial memory or potential mechanisms by which androgens may influence spatial memory, such as through brain derived neurotrophic factor (BDNF) regulation. My project tested the dose- dependence of dihydrotestosterone (DHT), an androgen derivative of T, on place learning and BDNF in adult male rats. To this end, DHT was given in three doses to castrated adult male rats (0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg s.c.), sesame oil was given as a negative control (0.4 ml/kg s.c.), and T was given as a positive control (2.0 mg/kg s.c.). Behavioral analysis was conducted on a plus maze using a place task. The number of trials to reach a criterion of 9 out of 10 correct trials and the number of correct choices in every block of 10 trials were measured. Each rat was tested for one hundred trials. Blood serum T concentrations, mBDNF concentrations, and proBDNF concentrations were determined with ELISA kits. Rats in the 2.0 mg/kg DHT and 2.0 mg/kg T groups reached criterion in fewer trials than rats for all other treatment groups and had more correct choices in several blocks of the learning curve. BDNF concentrations were not significantly influenced by treatment group in cortex, hippocampus, or striatum. These results implicate androgens in the formation and retrieval of spatial memory but do not eliminate the possibility that estrogens are significant in this process as well. Further, these results suggest that androgens regulate spatial memory through a mechanism other than regulation of BDNF concentration. Overall, this work is significant for its contribution to our knowledge on the cognitive effects of androgens. With this, we will be able to better care for the memory of individuals experiencing androgen-dependent impairment of spatial memory.