5α-reduced androgens may have actions in the hippocampus to enhance cognitive performance of male rats

Abstract

Androgens may improve cognitive performance; however, these effects and mechanisms of androgens are not well understood. Whether testosterone’s (T) effects on cognitive performance are mediated by its 5α-reduced, non-aromatizable metabolite dihydrotestosterone (DHT) and/or its 3α-hydroxysteroid dehydrogenase (3α-HSD) reduced metabolite 3α-androstanediol (3α-diol), was investigated. In Experiment 1, male rats that were gonadally intact, or gonadectomized (GDX) and DHT-replaced with a silastic capsule, had better performance in the inhibitory avoidance task, and higher plasma DHT and 3α-diol levels, compared to GDX rats. In Experiments 2–4, intra-hippocampal indomethacin, a 3α-HSD inhibitor, to intact or DHT-replaced, but not GDX, rats decreased performance in the inhibitory avoidance task and reduced hippocampal 3α-diol levels compared to that observed in rats with control implants. Thus, the 5α-reduced androgen DHT has cognitive-enhancing effects, independent of E 2, which are attenuated by a 3α-HSD inhibitor, indomethacin. These results suggest that 5α-reduced androgens may have actions in the hippocampus to improve cognitive performance.