Malhotra A K, Pinals D A, Weingartner H, Sirocco K, Missar C D, Pickar D, Breier A
Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, MD 20892, USA.
Neuropsychopharmacology. 1996 May;14(5):301-7. doi: 10.1016/0893-133X(95)00137-3.
A rapidly growing body of preclinical data has implicated the glutamatergic N-methyl-d-aspartate (NMDA) receptor in memory and other cognitive processes. There is comparatively less information about this receptor system in human cognition. We examined the effects of subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, on two forms of memory, free recall and recognition, as well as attention and behavior in a double-blind, placebo-controlled, 1-hour infusion in 15 healthy volunteers. Ketamine produced decrements in free recall, recognition memory, and attention. In addition, ketamine induced a brief psychosis in our healthy volunteers marked by thought disorder and withdrawal-retardation. Ketamine-induced memory impairments were not accounted for by changes in subject's attention and were not significantly related to psychosis ratings. These data suggest that the NMDA receptor plays a direct role in two types of explicit memory. The implications of these data for the pathophysiology of schizophrenia are discussed.
越来越多的临床前数据表明，谷氨酸能N-甲基-D-天冬氨酸（NMDA）受体与记忆及其他认知过程有关。关于该受体系统在人类认知方面的信息相对较少。我们在15名健康志愿者中进行了一项双盲、安慰剂对照、为时1小时的输注研究，考察了亚麻醉剂量的氯胺酮（一种非竞争性NMDA受体拮抗剂）对两种记忆形式（自由回忆和识别）以及注意力和行为的影响。氯胺酮导致自由回忆、识别记忆和注意力下降。此外，氯胺酮在我们的健康志愿者中诱发了短暂的精神病，其特征为思维紊乱和退缩迟缓。氯胺酮引起的记忆损害不能用受试者注意力的变化来解释，且与精神病评分无显著相关性。这些数据表明，NMDA受体在两种外显记忆类型中起直接作用。本文讨论了这些数据对精神分裂症病理生理学的意义。
