Department of Anesthesiology and Pain Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
J Neurosci. 2013 Jan 23;33(4):1577-88. doi: 10.1523/JNEUROSCI.1749-12.2013.
GluA1 subunits of AMPA glutamate receptors are implicated in the synaptic plasticity induced by drugs of abuse for behaviors of drug addiction, but GluA1 roles in emotional learning and memories of drug reward in the development of drug addiction remain unclear. In this study of the central nucleus of the amygdala (CeA), which is critical in emotional learning of drug reward, we investigated how adaptive changes in the expression of GluA1 subunits affected the learning process of opioid-induced context-reward association (associative learning) for the acquisition of reward-related behavior. In CeA neurons, we found that CeA GluA1 expression was significantly increased 2 h after conditioning treatment with morphine, but not 24 h after the conditioning when the behavior of conditioned place reference (CPP) was fully established in rats. Adenoviral overexpression of GluA1 subunits in CeA accelerated associative learning, as shown by reduced minimum time of morphine conditioning required for CPP acquisition and by facilitated CPP extinction through extinction training with no morphine involved. Adenoviral shRNA-mediated downregulation of CeA GluA1 produced opposite effects, inhibiting the processes of both CPP acquisition and CPP extinction. Adenoviral knockdown of CeA GluA2 subunits facilitated CPP acquisition, but did not alter CPP extinction. Whole-cell recording revealed enhanced electrophysiological properties of postsynaptic GluA2-lacking AMPA receptors in adenoviral GluA1-infected CeA neurons. These results suggest that increased GluA1 expression of CeA AMPA receptors facilitates the associative learning of context-drug reward, an important process in both development and relapse of drug-seeking behaviors in drug addiction.
AMPA 谷氨酸受体的 GluA1 亚基参与了药物滥用引起的突触可塑性，这种突触可塑性与药物成瘾的行为有关，但 GluA1 在药物奖赏的情绪学习和记忆中的作用在药物成瘾的发展中仍不清楚。在本研究中，我们研究了杏仁中央核（CeA），它在药物奖赏的情绪学习中起着关键作用，研究了 GluA1 亚基表达的适应性变化如何影响阿片类药物诱导的情境-奖赏关联（联想学习）的学习过程，从而获得与奖赏相关的行为。在 CeA 神经元中，我们发现吗啡条件处理后 2 小时，CeA GluA1 表达显著增加，但在条件处理后 24 小时，当大鼠的条件位置参考（CPP）行为完全建立时，CeA GluA1 表达没有增加。在 CeA 中过表达 GluA1 亚基加速了联想学习，表现为 CPP 获得所需的吗啡条件时间减少，以及通过无吗啡参与的消退训练促进 CPP 消退。CeA GluA1 的腺病毒 shRNA 介导的下调产生了相反的效果，抑制了 CPP 获得和 CPP 消退的过程。CeA GluA2 亚基的腺病毒敲低促进了 CPP 的获得，但不改变 CPP 的消退。全细胞记录显示，在腺病毒 GluA1 感染的 CeA 神经元中，缺乏 GluA2 的 AMPA 受体的电生理特性增强。这些结果表明，CeA AMPA 受体的 GluA1 表达增加促进了情境-药物奖赏的联想学习，这是药物成瘾中药物寻求行为的发展和复发的一个重要过程。
