Hara Y, Pickel V M
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University 411 East 69th Street KB-410, New York, NY 10021, USA.
Neuroscience. 2007 Jun 8;146(4):1593-605. doi: 10.1016/j.neuroscience.2007.04.005. Epub 2007 May 9.
Prepulse inhibition of the startle response to auditory stimulation (AS) is a measure of sensorimotor gating that is disrupted by the dopamine D1/D2 receptor agonist, apomorphine. The apomorphine effect on prepulse inhibition is ascribed in part to altered synaptic transmission in the limbic-associated shell and motor-associated core subregions of the nucleus accumbens (Acb). We used electron microscopic immunolabeling of dopamine D1 receptors (D1Rs) in the Acb shell and core to test the hypothesis that region-specific redistribution of D1Rs is a short-term consequence of AS and/or apomorphine administration. Thus, comparisons were made in the Acb of rats killed 1 h after receiving a single s.c. injection of vehicle (VEH) or apomorphine (APO) alone or in combination with startle-evoking AS (VEH+AS, APO+AS). In both regions of all animals, the D1R immunoreactivity was present in somata and large, as well as small, presumably more distal dendrites and dendritic spines. In the Acb shell, compared with the VEH+AS group, the APO+AS group had more spines containing D1R immunogold particles, and these particles were more prevalent on the plasma membranes. This suggests movement of D1Rs from distal dendrites to the plasma membrane of dendritic spines. Small- and medium-sized dendrites also showed a higher plasmalemmal density of D1R in the Acb shell of the APO+AS group compared with the APO group. In the Acb core, the APO+AS group had a higher plasmalemmal density of D1R in medium-sized dendrites compared with the APO or VEH+AS group. Also in the Acb core, D1R-labeled dendrites were significantly smaller in the VEH+AS group compared with all other groups. These results suggest that alerting stimuli and apomorphine synergistically affect distributions of D1R in Acb shell and core. Thus adaptations in D1R distribution may contribute to sensorimotor gating deficits that can be induced acutely by apomorphine or develop over time in schizophrenia.
对听觉刺激（AS）的惊吓反应的前脉冲抑制是一种感觉运动门控的测量方法，它会被多巴胺D1/D2受体激动剂阿扑吗啡破坏。阿扑吗啡对前脉冲抑制的影响部分归因于伏隔核（Acb）边缘相关壳区和运动相关核心亚区突触传递的改变。我们使用对Acb壳区和核心区多巴胺D1受体（D1Rs）进行电子显微镜免疫标记，以检验D1Rs的区域特异性重新分布是AS和/或给予阿扑吗啡的短期结果这一假设。因此，对在接受单次皮下注射溶剂（VEH）或阿扑吗啡（APO）单独或与诱发惊吓的AS联合注射（VEH+AS、APO+AS）1小时后处死的大鼠的Acb进行了比较。在所有动物的两个区域中，D1R免疫反应性存在于胞体以及大的和小的、可能更远端的树突和树突棘中。在Acb壳区，与VEH+AS组相比，APO+AS组含有D1R免疫金颗粒的棘更多，并且这些颗粒在质膜上更普遍。这表明D1Rs从远端树突移动到树突棘的质膜。与APO组相比，APO+AS组Acb壳区中小树突的D1R质膜密度也更高。在Acb核心区，与APO组或VEH+AS组相比，APO+AS组中型树突的D1R质膜密度更高。同样在Acb核心区，与所有其他组相比，VEH+AS组中D1R标记的树突明显更小。这些结果表明，警觉刺激和阿扑吗啡协同影响Acb壳区和核心区D1R的分布。因此，D1R分布的适应性变化可能导致感觉运动门控缺陷，这种缺陷可由阿扑吗啡急性诱发或在精神分裂症中随时间发展。
