Effects of dihydrotestosterone on response learning in adult male rats

Previous studies have shown that testosterone has a positive, dose-dependent effect on spatial memory performance in adult male rats. In particular, rats injected with low doses of testosterone perform better on spatial tasks using the response strategy. The effects of testosterone on spatial memory and learning may be linked to its metabolism in the brain, which can either take an androgen-dependent or estrogen-dependent pathway. To evaluate the involvement of an androgen-dependent pathway in spatial memory enhancement, I tested the performance of bilaterally castrated male rats (n=6-8/group) injected daily with oil (as a vehicular control), 0.5mg/kg testosterone (as a testosterone control), or one of three doses of DHT (0.5mg/kg, 1.0 mg/kg, and 2.0 mg/kg) on a response task via a plus maze. Brain tissue was extracted 24 h following behavioral testing, and assayed for levels of brain-derived neurotropic factor (BDNF) in the prefrontal cortex, hippocampus and striatum using ELISAs. In the plus-maze, I found that both a low (0.5mg/kg) and a medium dose of DHT (1.0mg/kg) exerted significant positive effects on response learning performance. Interestingly, the 0.5mg/kg testosterone group performed significantly better than all treatment groups except for the 1.0mg/kg DHT group. Overall, the results of this study did not completely align with the testosterone dose-dependent effects on response learning found in past studies, suggesting that there may exist putative androgen-estrogen interaction in response learning. While the BDNF assays did not indicate significant differences in proBDNF and mBDNF among the different treatment groups, preliminary analysis suggests that DHT and Testosterone affect the BDNF pathway in different ways. The results suggest that while different doses of DHT affect rat performance on response tasks, its effects do not fully replicate testosterone-mediated spatial memory improvement. Instead, the effects of testosterone may also depend on the estrogen-dependent metabolic pathway. Future work will examine the role of estradiol on response tasks.