Abstract:
: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.
journal_name
Neurobiol Learn Memjournal_title
Neurobiology of learning and memoryauthors
Edinger KL,Frye CAdoi
10.1016/j.nlm.2006.07.001subject
Has Abstractpub_date
2007-01-01 00:00:00pages
78-85issue
1eissn
1074-7427issn
1095-9564pii
S1074-7427(06)00082-7journal_volume
87pub_type
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