PMID- 16904920
OWN - NLM
STAT- MEDLINE
DCOM- 20070222
LR  - 20231106
IS  - 1074-7427 (Print)
IS  - 1095-9564 (Electronic)
IS  - 1074-7427 (Linking)
VI  - 87
IP  - 1
DP  - 2007 Jan
TI  - Androgens' effects to enhance learning may be mediated in part through actions at 
      estrogen receptor-beta in the hippocampus.
PG  - 78-85
AB  - Testosterone (T) may enhance cognitive performance. However, its mechanisms are 
      not well understood. First, we hypothesized that if T's effects are mediated in 
      part through actions of its 5alpha-reduced metabolites, dihydrotestosterone (DHT) 
      and/or 3alpha-androstanediol (3alpha-diol) in the hippocampus, then T, DHT, and 
      3alpha-diol-administration directly to the hippocampus should enhance learning 
      and memory in the inhibitory avoidance task. In order to test this hypothesis, 
      gonadectomized (GDX) male rats were administered T, DHT, or 3alpha-diol via 
      intrahippocampal inserts immediately following training in the inhibitory 
      avoidance task. We found that T tended to increase, and DHT and 3alpha-diol 
      significantly increased, performance in the inhibitory avoidance task compared to 
      vehicle-administered GDX rats. Second, we hypothesized that, if androgens' 
      effects are due in part to actions of 3alpha-diol in the hippocampus, then 
      systemic or intrahippocampal administration of 3alpha-diol should significantly 
      enhance cognitive performance of GDX male rats. Third, we hypothesized that, if 
      androgen metabolites can have actions at estrogen receptors (ERs) in the 
      hippocampus, then administration of ER antisense oligonucleotides (AS-ODNs) 
      directly to the hippocampus of GDX, 3alpha-diol replaced, rats would decrease 
      learning in the inhibitory avoidance task. We found that intrahippocampal 
      administration of AS-ODNs for ERbeta, but not ERalpha, significantly decreased 
      learning and memory of 3alpha-diol replaced rats. Together, these findings 
      suggest that T's effects to enhance learning and memory may take place, in part, 
      through actions of its metabolite, 3alpha-diol, at ERbeta in the dorsal 
      hippocampus.
FAU - Edinger, Kassandra L
AU  - Edinger KL
AD  - Department of Psychology, The University at Albany-SUNY, Life Sciences Research 
      Building Rm 1058, 1400 Washington Avenue, Albany, NY 12222, USA.
FAU - Frye, Cheryl A
AU  - Frye CA
LA  - eng
GR  - R01 MH067698/MH/NIMH NIH HHS/United States
GR  - 06769801/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20060814
PL  - United States
TA  - Neurobiol Learn Mem
JT  - Neurobiology of learning and memory
JID - 9508166
RN  - 0 (Estrogen Receptor beta)
RN  - 3XMK78S47O (Testosterone)
SB  - IM
MH  - Animals
MH  - Avoidance Learning/*physiology
MH  - Estrogen Receptor beta/*metabolism
MH  - Hippocampus/*metabolism
MH  - Male
MH  - Rats
MH  - Rats, Long-Evans
MH  - Reaction Time/physiology
MH  - Testosterone/*metabolism
PMC - PMC3633449
MID - NIHMS452844
EDAT- 2006/08/15 09:00
MHDA- 2007/02/23 09:00
PMCR- 2013/04/23
CRDT- 2006/08/15 09:00
PHST- 2006/04/26 00:00 [received]
PHST- 2006/06/14 00:00 [revised]
PHST- 2006/07/02 00:00 [accepted]
PHST- 2006/08/15 09:00 [pubmed]
PHST- 2007/02/23 09:00 [medline]
PHST- 2006/08/15 09:00 [entrez]
PHST- 2013/04/23 00:00 [pmc-release]
AID - S1074-7427(06)00082-7 [pii]
AID - 10.1016/j.nlm.2006.07.001 [doi]
PST - ppublish
SO  - Neurobiol Learn Mem. 2007 Jan;87(1):78-85. doi: 10.1016/j.nlm.2006.07.001. Epub 
      2006 Aug 14.