Department of Neuroscience, University of Florida College of Medicine, McKnight Brain Institute, Gainesville, FL 32610, USA.
Neuroscience. 2012 Oct 25;223:45-55. doi: 10.1016/j.neuroscience.2012.07.037. Epub 2012 Aug 2.
The NR1 subunit of the NMDA receptor can be alternatively spliced by the insertion or removal of the N1, C1, C2, or C2' regions. Morphine dependence and withdrawal were previously demonstrated to lower N1 and C2' in the accumbens and lower N1, C1, and C2' in the amygdala (AMY). Withdrawal has also been demonstrated to increase motivational and anxiety/stress behaviors in rats. We tested the hypothesis that NR1 splicing would be associated with these behaviors during an extended withdrawal period of 2 months. Motivation was measured using an operant orofacial assay at non-aversive temperatures (37°C) while anxiety and stress were measured by examining this behavior at aversive temperatures (46°C). Lower C1 and C2 expression levels were observed in the AMY in a subset of the population of withdrawn rats even after 2 months of morphine withdrawal. These subsets were associated with a hypersensitivity to adverse conditions which may reflect long-term alterations in the withdrawn population.
NMDA 受体的 NR1 亚基可通过插入或缺失 N1、C1、C2 或 C2' 区域进行选择性剪接。先前已经证明吗啡依赖和戒断会降低伏隔核中的 N1 和 C2'，以及杏仁核（AMY）中的 N1、C1 和 C2'。戒断还被证明会增加大鼠的动机和焦虑/应激行为。我们假设在长达 2 个月的戒断期间，NR1 剪接与这些行为有关。在非厌恶温度（37°C）下使用操作性口腔测定法测量动机，而在厌恶温度（46°C）下检查这种行为来测量焦虑和应激。即使在吗啡戒断 2 个月后，在一部分戒断大鼠的 AMY 中也观察到 C1 和 C2 表达水平降低。这些亚群与对不良条件的敏感性增加有关，这可能反映了戒断人群的长期变化。
