Article Figures & Data
Figures
- Figure 1.
Ethanol-mediated neurosteroidogenesis results from activation of NMDARs and 5α-reductase. A, Immunostaining against 5α-reduced neurosteroids was observed in cell bodies of pyramidal neurons in naive hippocampal slices. The neurosteroid staining was enhanced by 15 min incubation with 60 mm ethanol but blocked by 1 μm finasteride, 1 μm dutasteride, and 50 μm APV. Scale bar, 25 μm. B, Summary of immunostaining studies shows fluorescence intensity (arbitrary units) as mean ± SEM. p values are calculated by Holm–Sidek post hoc test, n = 5; *p < 0.001.
- Figure 2.
Ethanol-mediated LTP inhibition involves activation of NMDARs and 5α-reductase. A, In control slices, LTP is readily induced (white circles) by a 100 Hz × 1 s high-frequency stimulation (HFS, arrow). Fifteen minute administration of 60 mm ethanol (black bar) inhibited LTP induction (black circles), while finasteride (red triangles) or dutasteride (pink squares) overcame LTP inhibition. B, Ethanol's inhibition of LTP (black triangles) persisted for at least 30 min after washout (black bar). This inhibitory effect was prevented by coadministration of APV (blue bar) with ethanol (blue triangles). Traces depict EPSPs before (dashed lines) and 60 min after HFS (solid lines). Calibration, 1 mV, 5 ms.
- Figure 3.
NMDA promotes neurosteroidogenesis and inhibits LTP via effects on neurosteroids. A, In naive slices, cell bodies of CA1 pyramidal neurons were diffusely positive for 5α-reduced steroids. The staining was enhanced when incubated with 1 μm NMDA for 5 min but was inhibited by pretreatment with 1 μm finasteride or with 1 μm dutasteride. Scale bar, 25 μm. B, Summary of immunohistological studies shows fluorescence intensity as mean ± SEM (n = 5). p value was calculated by Holm–Sidak post hoc method; *p < 0.001.
- Figure 4.
NMDA-mediated LTP inhibition involves neurosteroidogenesis. A, Five minute treatment with 1 μm NMDA (black bar) before a high-frequency stimulation (HFS, arrow) was sufficient to block CA1 LTP (black triangles). This LTP inhibition was overcome by 1 μm finasteride (red triangles) or 1 μm dutasteride (pink squares). B, The effects of 1 μm NMDA on LTP inhibition lasted at least 30 min following washout (black triangles). Coadministration of APV (blue bar) overcame NMDA's inhibition of LTP (blue triangle). Traces depict EPSPs before (dashed lines) and 60 min after HFS (solid lines). Calibration, 1 mV, 5 ms.
