The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: Distinct mechanisms?
The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: Distinct mechanisms?
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DOI：
10.1073/pnas.241503698
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发表时间：
2001-11-20
影响因子：
11.1
通讯作者：
Baulieu, EE
中科院分区：
文献类型：
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作者：
Akwa, Y;Ladurelle, N;Baulieu, EE
神经甾体硫酸双烯醇酮（PREGS）在生理和药理水平上对记忆功能具有活性的证明，使我们通过在Y型迷宫中使用两次试验识别任务详细研究了类固醇对空间工作记忆的影响，Y型迷宫是一种基于啮齿动物探索新环境的自然驱动力的范例。在年轻的成年雄性Sprague-Dawley大鼠和Swiss小鼠中进行的剂量反应研究，在获得后侧脑室注射类固醇后，显示记忆性能呈U型倒置曲线，并表明大鼠的反应性高于小鼠。值得注意的是，合成的（-）对映体的PREGS不仅也显示promnesiant活性，但其效力是10倍以上的天然类固醇。DL-2-氨基-5-磷酸戊酸（N-甲基-D-天冬氨酸受体的竞争性选择性拮抗剂）的脑室内联合给药实验消除了PREGS的记忆增强作用，但没有消除PREGS对映体的记忆增强作用，引起了对映体的选择性N-甲基-D-天冬氨酸受体和/或两种对映体的促进功能的不同机制。
The demonstration that the neurosteroid pregnenolone sulfate (PREGS) is active on memory function at both the physiological and pharmacological levels led to us examining in detail the effects of the steroid on spatial working memory by using a two-trial recognition task in a Y-maze, a paradigm based on the natural drive in rodents to explore a novel environment. Dose-response studies in young male adult Sprague-Dawley rats and Swiss mice, after the postacquisition intracerebroventricular injection of steroid, showed an U-inverted curve for memory performance and indicated a greater responsiveness in rats compared with mice. Remarkably, the synthetic (-) enantiomer of PREGS not only also displayed promnesiant activity, but its potency was 10 times higher than that of the natural steroid. Intracerebroventricular coadministration experiments with DL-2-amino-5-phosphonovaleric acid, a competitive selective antagonist of the N-methyl-D-aspartate receptor, abolished the memory-enhancing effect of PREGS, but not that of the PREGS enantiomer, evoking enantiomeric selectivity at the N-methyl-D-aspartate receptor and/or different mechanisms for the promnestic function of the two enantiomers.