Electron microscopic dual labeling of high-affinity neurotensin and dopamine D2 receptors in the rat nucleus accumbens shell

Electron microscopic dual labeling of high-affinity neurotensin and dopamine D2 receptors in the rat nucleus accumbens shell
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DOI:
10.1002/syn.20018
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发表时间:
2004-06-01
期刊:
影响因子:
2.3
通讯作者:
Pickel, VM
Pickel, VM
中科院分区:
医学4区
文献类型:
--
作者:
Delle Donne, KT;Chan, J;Pickel, VM

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伏隔核(NAc)壳中的多巴胺D2受体(D2R)与精神分裂症和精神兴奋剂诱导的药物寻求行为有关,这两种行为都受到功能对立的高亲和力神经紧张素受体(NTS1)激活的影响。为了确定功能相关位点,我们检测了D2R和NTS1在大鼠脑NAc壳中的双电镜免疫细胞化学定位。每个受体的免疫标记与细胞质细胞器相关,或者更罕见的是在轴突和体树突的质膜上。一些轴突突起和许多树突突起将这两种受体定位。双标记的轴突末端通常与未标记的树突轮廓形成对称突触或同位接触。这些末端的形态表明它们含有抑制性氨基酸或多巴胺。其他仅表达NTS1或D2R的轴突没有突触特化,或主要在未标记的树突棘上形成不对称的兴奋型突触。此外,在含有NTS1的树突突触前观察到几个d2r免疫反应性终末。免疫标记NTS1和/或D2R的体树突具有NAc中抑制性棘突神经元的典型形态学特征。这些结果表明,NTS1和D2R的激活可以双重调节NAc壳中相同或不同表型轴突末端的递质释放。这些突触前受体以及突触后NTS1分布在含有或接受含有D2R的终端输入的神经元中,可能介导NAc中神经紧张素和多巴胺的相反作用。(C) 2004 Wiley-Liss, Inc。
The dopamine D2 receptor (D2R) in the nucleus accumbens (NAc) shell is implicated in schizophrenia and in psychostimulant-induced drug-seeking behavior, both of which are affected by activation of the functionally opposed high-affinity neurotensin receptor (NTS1). To determine the functionally relevant sites, we examined the dual electron microscopic immunocytochemical localization of D2R and NTS1 in the NAc shell of rat brain. Immunolabeling for each receptor was seen in association with cytoplasmic organelles, or more rarely, on the plasma membrane of both axonal and somatodendritic profiles. Some of the axonal and many of the dendritic processes colocalized the two receptors. The dually labeled axon terminals often formed symmetric synapses or appositional contacts with unlabeled dendritic profiles. The morphology of these terminals suggests that they contain either inhibitory amino acids or dopamine. Other axonal profiles expressing exclusively NTS1 or D2R were without synaptic specializations or formed asymmetric, excitatory-type synapses mainly on unlabeled dendritic spines. In addition, however, several D2R-immunoreactive terminals were observed presynaptic to dendrites containing NTS1. The somatodendritic profiles immunolabeled for NTS1 and/or D2R had morphological features typical of inhibitory spiny projection neurons in the NAc. These results suggest that activation of NTS1 and D2R can dually modulate transmitter release from the same or separate phenotypically distinct axon terminals in the NAc shell. These presynaptic receptors as well as the postsynaptic NTS1 distribution in neurons that also contain or receive input from terminals containing D2R may mediate the opposing actions of neurotensin and dopamine in the NAc. (C) 2004 Wiley-Liss, Inc.