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

Frye CA, Edinger KL, Seliga AM, Wawrzycki JM.
Department of Psychology,The University at Albany--SUNY,
1400 Washington Avenue, Albany, NY 12222, USA.
Psychoneuroendocrinology. 2004 Sep;29(8):1019-27.


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 5alpha-reduced, non-aromatizable metabolite dihydrotestosterone (DHT) and/or its 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) reduced metabolite 3alpha-androstanediol (3alpha-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 3alpha-diol levels, compared to GDX rats. In Experiments 2-4, intra-hippocampal indomethacin, a 3alpha-HSD inhibitor, to intact or DHT-replaced, but not GDX, rats decreased performance in the inhibitory avoidance task and reduced hippocampal 3alpha-diol levels compared to that observed in rats with control implants. Thus, the 5alpha-reduced androgen DHT has cognitive-enhancing effects, independent of E(2), which are attenuated by a 3alpha-HSD inhibitor, indomethacin. These results suggest that 5alpha-reduced androgens may have actions in the hippocampus to improve cognitive performance.

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