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

Psychoneuroendocrinology. 2004 Sep;29(8):1019-27. doi: 10.1016/j.psyneuen.2003.10.004.

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 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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism
  • Androstane-3,17-diol / metabolism*
  • Animals
  • Aromatase
  • Avoidance Learning / physiology*
  • Cognition / physiology
  • Dihydrotestosterone / metabolism*
  • Hippocampus / enzymology
  • Hippocampus / metabolism*
  • Male
  • Rats
  • Rats, Long-Evans
  • Testosterone / metabolism*

Substances

  • Dihydrotestosterone
  • Androstane-3,17-diol
  • Testosterone
  • Aromatase
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase