5alpha-reduced androgens may have actions in the hippocampus to enhance cognitive performance of male rats.
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.
Frye
Cheryl A
CA
Department of Psychology,The University at Albany--SUNY, 1400 Washington Avenue, Albany, NY 12222, USA. cafrye@cnsunix.albany.edu
Edinger
Kassandra L
KL
Seliga
Angela M
AM
Wawrzycki
JoAnna M
JM
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D015113:Androstane-3,17-diol / Q000378:metabolism*; D000818:Animals; D001141:Aromatase; D001362:Avoidance Learning / Q000502:physiology*; D003071:Cognition / Q000502:physiology; D013196:Dihydrotestosterone / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D013739:Testosterone / Q000378:metabolism*
D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; D013739:Testosterone; D001141:Aromatase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase