Hyperactivity of the dopaminergic system in NTS1 and NTS2 null mice.
Hyperactivity of the dopaminergic system in NTS1 and NTS2 null mice.
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DOI：
10.1016/j.neuropharm.2010.02.015
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发表时间：
2010-06
影响因子：
4.7
通讯作者：
Richelson, Elliott
中科院分区：
文献类型：
--
作者：
Liang, Yanqi;Boules, Mona;Li, Zhimin;Williams, Katrina;Miura, Tomofumi;Oliveros, Alfredo;Richelson, Elliott
关键词：
神经降压素 (NT) 是一种十三肽，主要通过两个 NT 受体 NTS1 和 NTS2 在中枢神经系统中充当神经调节剂。 NT、中脑多巴胺系统和多巴胺能投射的目标结构之间的功能解剖学相互作用已被研究。本研究使用缺乏 NTS1 (NTS1−/−) 或 NTS2 (NTS2−/−) 的小鼠来确定 NT 受体亚型对多巴胺能功能的影响。测定基础和安非他明刺激的运动活性。自由活动小鼠的体内微透析与 HPLC-ECD 相结合，用于检测基础和 d-安非他明刺激的纹状体细胞外多巴胺水平。进行多巴胺转运蛋白的体外放射性配体结合和突触体摄取测定，以测试纹状体突触前多巴胺转运蛋白的表达和功能。 NTS1−/− 和 NTS2−/− 小鼠具有较高的基线运动活性和较高的纹状体细胞外多巴胺水平。 NTS1−/− 小鼠表现出较高的运动活性和对 d-苯丙胺的反应，多巴胺释放过多。与野生型小鼠相比，NTS1−/− 和 NTS2−/− 小鼠纹状体中的多巴胺 D1 受体 mRNA 表达较低。纹状体中的多巴胺转运蛋白结合和多巴胺再摄取没有改变。因此，NTS1 或 NTS2 的缺乏会改变多巴胺能系统。讨论了多巴胺传递失调可能源于谷氨酸神经传递缺陷的可能性。这些数据强化了 NT 受体参与精神分裂症发病机制的假设，并为该疾病的生化变化提供了潜在的模型。
Neurotensin (NT) is a tridecapeptide that acts as a neuromodulator in the central nervous system mainly through two NT receptors, NTS1 and NTS2. The functional-anatomical interactions between NT, the mesotelencephalic dopamine system, and structures targeted by dopaminergic projections have been studied. The present study was conducted to determine the effects of NT receptor subtypes on dopaminergic function with the use of mice lacking either NTS1 (NTS1−/−) or NTS2 (NTS2−/−). Basal and amphetamine-stimulated locomotor activity was determined. In vivo microdialysis in freely moving mice, coupled with HPLC-ECD, was used to detect basal and d-amphetamine-stimulated striatal extracellular dopamine levels. In vitro radioligand binding and synaptosomal uptake assays for the dopamine transporters were conducted to test for the expression and function of the striatal pre-synaptic dopamine transporter. NTS1−/− and NTS2−/− mice had higher baseline locomotor activity and higher basal extracellular dopamine levels in striatum. NTS1−/− mice showed higher locomotor activity and exaggerated dopamine release in response to d-amphetamine. Both NTS1−/− and NTS2−/− mice exhibited lower dopamine D1 receptor mRNA expression in the striatum relative to wild type mice. Dopamine transporter binding and dopamine reuptake in striatum were not altered. Therefore, lack of either NTS1 or NTS2 alters the dopaminergic system. The possibility that the dysregulation of dopamine transmission might stem from a deficiency in glutamate neurotransmission is discussed. The data strengthen the hypothesis that NT receptors are involved in the pathogenesis of schizophrenia and provide a potential model for the biochemical changes of the disease.
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影响因子：
5
作者：
Boules, M;Warrington, L;Richelson, E
通讯作者：
Richelson, E
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：
2.7
作者：
Carlier, PR;Lo, MMC;Sharma, TA
通讯作者：
Sharma, TA
影响因子：
2.3
作者：
Delle Donne, KT;Chan, J;Pickel, VM
通讯作者：
Pickel, VM
影响因子：
2.9
作者：
Cusack, B;Boules, M;Richelson, E
通讯作者：
Richelson, E