Age-specific neurotoxicity in the rat associated with NMDA receptor blockade: Potential relevance to schizophrenia?
Age-specific neurotoxicity in the rat associated with NMDA receptor blockade: Potential relevance to schizophrenia?
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DOI：
10.1016/0006-3223(95)00046-1
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发表时间：
1995-12-15
影响因子：
10.6
通讯作者：
Olney, JW
中科院分区：
文献类型：
--
作者：
Farber, NB;Wozniak, DF;Olney, JW
阻断谷氨酸受体n -甲基- d -天冬氨酸（NMDA）亚型的药物可诱导成人精神分裂症样精神病，并损伤或杀死成年大鼠脑皮质边缘区域的几个神经元。对NMDA拮抗剂氯胺酮的拟精神作用的易感性在儿童中很少或不存在，在成年早期变得最大。我们研究了不同年龄的大鼠对强效NMDA拮抗剂MK-801的神经毒性作用的敏感性。脆弱性被发现是年龄依赖的，大约在青春期（45天大）开始，并在成年早期达到最大。这种年龄依赖性（在青春期晚期开始易感性）与人类氯胺酮诱导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，NMDA拮抗剂神经毒性和拟精神作用的机制，也可能在精神分裂症中发挥作用。
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 mt 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.