Similarities in the behavior and molecular deficits in the frontal cortex between the neurotensin receptor subtype 1 knockout mice and chronic phencyclidine-treated mice: relevance to schizophrenia.
Similarities in the behavior and molecular deficits in the frontal cortex between the neurotensin receptor subtype 1 knockout mice and chronic phencyclidine-treated mice: relevance to schizophrenia.
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DOI：
10.1016/j.nbd.2010.07.011
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发表时间：
2010-11
影响因子：
6.1
通讯作者：
Richelson E
中科院分区：
文献类型：
--
作者：
Li Z;Boules M;Williams K;Gordillo A;Li S;Richelson E
许多证据表明，靶向神经降压素（NT）系统可能为精神分裂症提供一种新的和有希望的治疗方法。我们最近的工作表明：NTS 1基因敲除（NTS 1 −/−）小鼠可通过研究NTS 1受体缺失对苯丙胺诱导的多动和神经化学变化的影响，为研究精神分裂症提供潜在的动物模型。这些数据表明，高多巴胺能状态类似于精神分裂症中报告的过度纹状体DA活性。本研究的目的是确定NTS 1 −/−小鼠是否也有类似的行为变化，前额叶神经递质和蛋白质表达，如野生型（WT）小鼠用拟精神病药物苯环利定（PCP）治疗，精神分裂症的动物模型。我们的研究结果表明，未经治疗的NTS 1 −/−小鼠和长期接受PCP治疗的WT小鼠之间存在许多相似之处（与未处理的WT小鼠相比）：1）较低的PCP诱导的运动活动; 2）在强迫游泳试验和悬尾试验中相似的类似的逃避行为; 3）较低的前额叶谷氨酸水平; 4）较少的PCP诱导的内侧前额叶皮质（mPFC）中的多巴胺释放; 5）多巴胺D1、D2和NMDAR 2A的mRNA和蛋白表达下调。因此，这些数据加强了NTS 1 −/−小鼠是精神分裂症动物模型的假设，特别是前额叶皮质功能障碍。此外，慢性PCP给药后，NTS 1 −/−小鼠的DA D1受体上调，结果表明mPFC中NTS 1/DA D1可能相互作用，导致慢性PCP诱导的精神分裂症样体征。
Much evidence suggests that targeting the neurotensin (NT) system may provide a novel and promising treatment for schizophrenia. Our recent work shows that: NTS1 knockout (NTS1−/−) mice may provide a potential animal model for studying schizophrenia by investigating the effect of deletion NTS1 receptor on amphetamine-induced hyperactivity and neurochemical changes. The data indicate a hyper-dopaminergic state similar to the excessive striatal DA activity reported in schizophrenia. The present study was done to determine if NTS1−/− mice also have similar changes in behavior, in prefrontal neurotransmitters, and in protein expression, as observed in wild type (WT) mice treated with the psychotomimetic phencylclidine (PCP), an animal model for schizophrenia. Our results showed many similarities between untreated NTS1−/− mice and WT mice chronically treated with PCP (as compared with untreated WT mice): 1) lower PCP-induced locomotor activity; 2) similar avolition-like behavior in forced-swim test and tail suspension test; 3) lower prefrontal glutamate levels; 4) less PCP-induced dopamine release in medial prefrontal cortex (mPFC); and 5) down-regulation of mRNA and protein for DA D1, DA D2, and NMDAR2A in mPFC. Therefore, these data strengthen the hypothesis that the NTS1−/− mouse is an animal model of schizophrenia, particularly for dysfunction of the prefrontal cortex. In addition, after chronic PCP administration, the DA D1 receptor was up-regulated in NTS1−/− mice, results which suggest a possible interaction of NTS1/DA D1 in mPFC contributing to chronic PCP-induced schizophrenia-like signs.
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影响因子：
5.3
作者：
Adams, B;Moghaddam, B
通讯作者：
Moghaddam, B
DOI：
10.1111/j.1749-6632.1992.tb27350.x
发表时间：
1992-10-22
期刊：
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES-SERIES
影响因子：
--
作者：
FUXE, K;VONEULER, G;BENFENATI, F
通讯作者：
BENFENATI, F
影响因子：
4.7
作者：
Leonetti, M;Brun, P;Suaud-Chagny, MF
通讯作者：
Suaud-Chagny, MF
影响因子：
2.9
作者：
Li, Zhimin;Boules, Mona;Richelson, Elliott
通讯作者：
Richelson, Elliott
影响因子：
2.7
作者：
Hertel, P;Mathe, JM;Svensson, TH
通讯作者：
Svensson, TH