The effects of DHEA, 3β-hydroxy-5α-androstane-6,17-dione, and 7-amino-DHEA analogues on short term and long term memory in the mouse

Neurosteroids have been reported to modulate memory processes in rodents. Three analogues of dehydroepiandrosterone (DHEA), two of them previously described (7β-aminoDHEA and 7β-amino-17-ethylenedioxy-DHEA), and a new one (3β-hydroxy-5α-androstane-6,17-dione) were synthesized, and their effects were evaluated on memory. This study examined their effects on long term and short term memory in male (6 weeks old) NMRI mice in comparison with the reference drug. Long term memory was assessed using the passive avoidance task and short term memory (spatial working memory) using the spontaneous alternation task in a Y maze. Moreover, the effects of DHEA and its analogues on spontaneous locomotion were measured. In all tests, DHEA and analogues were injected at three equimolar doses (0.300–1.350–6.075 μM/kg). DHEA and its three analogues administered immediately post-training at the highest doses (6.075 μM/kg, s.c.) improved retention in passive avoidance test. Without effect per se in the spatial working memory task, the four compounds failed to reverse scopolamine (1 mg/kg, i.p.)-induced deficit in spontaneous alternation. These data suggested an action of DHEA and analogues in consolidation of long term memory particularly when emotional components are implied. Moreover, data indicated that pharmacological modulation of DHEA as performed in this study provides derivatives giving the same mnemonic profile than reference molecule.