Miyamoto Seiya, Snouwaert John N, Koller Beverly H, Moy Sheryl S, Lieberman Jeffrey A, Duncan Gary E
Department of Psychiatry, the Mental Health and Neuroscience Clinical Research Center, USA.
Neuropsychopharmacology. 2004 Dec;29(12):2180-8. doi: 10.1038/sj.npp.1300548.
A mouse strain has been developed that expresses low levels of the NR1 subunit of the NMDA receptor. These mice are a model of chronic developmental NMDA receptor hypofunction and may therefore have relevance to the hypothesized NMDA receptor hypofunction in schizophrenia. Many schizophrenia patients show exaggerated behavioral and neuronal responses to amphetamine compared to healthy subjects. Studies were designed to determine if the NR1-deficient mice would exhibit enhanced sensitivity to amphetamine. Effects of amphetamine on behavioral activation and Fos induction were compared between the NR1-deficient mice and wild-type controls. The NR1 hypomorphic mice and controls exhibited similar locomotor activation after administration of amphetamine at 2 mg/kg. The mutant mice showed slightly reduced peak locomotor activity and slightly increased stereotypy after 4 mg/kg amphetamine. There were no differences in Fos induction in response to amphetamine in the caudate putamen, nucleus accumbens, medial or central amygdala nuclei, or bed nucleus of the stria terminalis. However, amphetamine-induced Fos was substantially attenuated in the medial frontal (infralimbic) and cingulate cortices, basolateral amygdala, and in the lateral septum of the mutant mice. The results suggest a neuroanatomically selective activation deficit to amphetamine challenge in the NR1-deficient mice.
已经培育出一种表达低水平NMDA受体NR1亚基的小鼠品系。这些小鼠是慢性发育性NMDA受体功能低下的模型，因此可能与精神分裂症中假设的NMDA受体功能低下有关。与健康受试者相比，许多精神分裂症患者对苯丙胺表现出夸张的行为和神经元反应。研究旨在确定NR1缺陷小鼠是否对苯丙胺表现出更高的敏感性。比较了NR1缺陷小鼠和野生型对照中苯丙胺对行为激活和Fos诱导的影响。给予2mg/kg苯丙胺后，NR1低表达小鼠和对照表现出相似的运动激活。给予4mg/kg苯丙胺后，突变小鼠的运动峰值活性略有降低，刻板行为略有增加。在尾壳核、伏隔核、内侧或中央杏仁核或终纹床核中，对苯丙胺反应的Fos诱导没有差异。然而，在突变小鼠的内侧额叶（边缘下）和扣带回皮质、基底外侧杏仁核以及外侧隔区，苯丙胺诱导的Fos明显减弱。结果表明，NR1缺陷小鼠对苯丙胺刺激存在神经解剖学上的选择性激活缺陷。
