Farber N B, Wozniak D F, Price M T, Labruyere J, Huss J, St Peter H, Olney J W
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Biol Psychiatry. 1995 Dec 15;38(12):788-96. doi: 10.1016/0006-3223(95)00046-1.
Agents that block the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor induce a schizophrenialike psychosis in adult humans and injure or kill neurons in several corticolimbic regions of the adult rat brain. Susceptibility to the psychotomimetic effects of the NMDA antagonist, ketamine is minimal or absent in children and becomes maximal in early adulthood. We examined the sensitivity of rats at various ages to the neurotoxic effects of the powerful NMDA antagonist, MK-801. Vulnerability was found to be age dependent, having onset at approximately puberty (45 days of age) and becoming maximal in early adulthood. This age-dependency profile (onset of susceptibility in late adolescence) in the rat is similar to that for ketamine-induced psychosis or schizophrenia in humans. These findings suggest that NMDA receptor hypofunction, the mechanism underlying the neurotoxic and psychotomimetic actions of NMDA antagonists, may also play a role in schizophrenia.
阻断谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型的药物，可在成年人类中诱发类似精神分裂症的精神病，并在成年大鼠大脑的几个皮质边缘区域损伤或杀死神经元。儿童对NMDA拮抗剂氯胺酮的拟精神病作用的易感性极小或不存在，而在成年早期达到最大。我们研究了不同年龄大鼠对强效NMDA拮抗剂MK-801神经毒性作用的敏感性。发现易损性与年龄有关，约在青春期（45日龄）开始出现，并在成年早期达到最大。大鼠的这种年龄依赖性特征（青春期后期开始出现易感性）与人类氯胺酮诱发的精神病或精神分裂症相似。这些发现表明，NMDA受体功能低下作为NMDA拮抗剂神经毒性和拟精神病作用的潜在机制，可能也在精神分裂症中起作用。
