Delle Donne Karen T, Chan June, Boudin Helene, Pélaprat Didier, Rostène William, Pickel Virginia M
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA.
Synapse. 2004 Jun 1;52(3):176-87. doi: 10.1002/syn.20018.
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.
伏隔核（NAc）壳中的多巴胺D2受体（D2R）与精神分裂症以及精神兴奋剂诱导的觅药行为有关，而这两者都会受到功能相反的高亲和力神经降压素受体（NTS1）激活的影响。为了确定功能相关位点，我们检查了大鼠脑NAc壳中D2R和NTS1的双电子显微镜免疫细胞化学定位。在细胞质细胞器上可看到每种受体的免疫标记，或更罕见地，在轴突和树突状结构的质膜上看到。一些轴突和许多树突状突起共定位了这两种受体。双重标记的轴突终末常常与未标记的树突状结构形成对称突触或并列接触。这些终末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的轴突结构没有突触特化，或主要在未标记的树突棘上形成不对称的兴奋性突触。然而，此外，还观察到几个D2R免疫反应性终末位于含有NTS1的树突的突触前。对NTS1和/或D2R进行免疫标记的树突状结构具有NAc中抑制性棘状投射神经元的典型形态特征。这些结果表明，NTS1和D2R的激活可以双重调节来自NAc壳中相同或不同表型的轴突终末的递质释放。这些突触前受体以及在也含有或接受来自含有D2R的终末输入的神经元中的突触后NTS1分布，可能介导了神经降压素和多巴胺在NAc中的相反作用。
