Flood J F, Smith G E, Roberts E
Psychobiology Research Laboratory, Veterans Administration Hospital, Sepulveda, CA 91343.
Brain Res. 1988 May 3;447(2):269-78. doi: 10.1016/0006-8993(88)91129-8.
Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), major naturally occurring precursors of both androgenic and estrogenic steroids, were shown in the present study to have convincing memory enhancing effects in mice. Post-training intracerebroventricular (i.c.v.) administration of DHEA in dimethylsulfoxide (2 microliters) prevented the amnesia for footshock active avoidance training (FAAT) caused by the same volume of dimethylsulfoxide alone. DHEAS significantly enhanced retention of FAAT in weakly trained mice whether injected i.c.v. or s.c. immediately post-training or given in the drinking water for a 2-week period. In the latter instance DHEAS was shown to facilitate retention of FAAT without enhancing acquisition. The maximally effective doses were: i.c.v., 162 ng/mouse; s.c., 700 micrograms/mouse; and oral, 1.45 mg/mouse/day. DHEAS administered i.c.v. occluded the amnestic effects of anisomycin (inhibitor of protein synthesis) and scopolamine (muscarinic cholinergic antagonist). There was a time-dependence of the facilitatory effects of post-training i.c.v. administration of DHEAS on retention of FAAT, significant enhancement of retention being observed when it was given either immediately (within 2 min) or at 30 and 60 min after training, but not at 90 or 120 min. DHEAS given i.c.v. also improved retention for step-down passive avoidance. In all instances, dose-dependent inverted U curves were obtained in a manner typical for memory enhancing substances. At a practical level, these experiments open new possibilities for the development of substances that may help in alleviating amnesic disorders in man.
脱氢表雄酮（DHEA）及其硫酸盐（DHEAS）是雄激素和雌激素类固醇的主要天然前体，本研究表明它们对小鼠具有显著的记忆增强作用。训练后经脑室注射（i.c.v.）二甲基亚砜（2微升）中的DHEA可预防仅注射相同体积二甲基亚砜所导致的足部电击主动回避训练（FAAT）失忆。无论是训练后立即经脑室注射还是皮下注射，或者在饮水中给予两周，DHEAS都能显著提高弱训练小鼠的FAAT保持率。在后一种情况下，DHEAS被证明可促进FAAT的保持而不增强习得。最大有效剂量分别为：经脑室注射，162纳克/只小鼠；皮下注射，700微克/只小鼠；口服，1.45毫克/只小鼠/天。经脑室注射DHEAS可消除茴香霉素（蛋白质合成抑制剂）和东莨菪碱（毒蕈碱胆碱能拮抗剂）的失忆作用。训练后经脑室注射DHEAS对FAAT保持的促进作用具有时间依赖性，在训练后立即（2分钟内）或30分钟和60分钟给予时，可观察到保持率显著提高，但在90分钟或120分钟时则无此效果。经脑室注射DHEAS也可改善递减式被动回避的保持。在所有情况下，均以记忆增强物质典型的方式获得了剂量依赖性的倒U形曲线。从实际应用角度来看，这些实验为开发可能有助于缓解人类失忆症的物质开辟了新的可能性。
