Department of Anatomy & Cell Biology, 468 Medical Science Building, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Eur J Neurosci. 2012 Jan;35(2):279-90. doi: 10.1111/j.1460-9568.2011.07943.x. Epub 2012 Jan 12.
The basolateral amygdala (BLA), ventral tegmental area and nucleus accumbens (NAc) form a functionally connected neural circuit involved in the processing of opiate-related reward and memory. Dopamine (DA) projections from the ventral tegmental area to the BLA modulate associative plasticity mechanisms within the BLA. However, the role of DA receptor signaling in the BLA and its functional outputs to the NAc during opiate reward processing is not currently understood. Using an unbiased place conditioning procedure, we measured the rewarding effects of morphine following intra-BLA microinfusions of specific DA D1 or D2 receptor agonists in either opiate-naive or opiate-dependent/withdrawn rats. Activation of intra-BLA D1 receptors strongly potentiated the behaviorally rewarding effects of opiates, only in the opiate-naive state. However, once opiate dependence and withdrawal occurred, the intra-BLA DA-mediated potentiation of opiate reward salience switched to a D2 receptor-dependent substrate. We next performed single-unit, in-vivo extracellular neuronal recordings in the NAc shell (NA shell), to determine if intra-BLA D1/D2 receptor activation may modulate the NA shell neuronal response patterns to morphine. Consistent with our behavioral results, intra-BLA D1 or D2 receptor activation potentiated NAc 'shell' (NA shell) neuronal responses to sub-reward threshold opiate administration, following the same functional boundary between the opiate-naive and opiate-dependent/withdrawn states. Finally, blockade of N-methyl-d-aspartate transmission within the NA shell blocked intra-BLA DA D1 or D2 receptor-mediated opiate reward potentiation. Our findings demonstrate a novel and functional DA D1/D2 receptor-mediated opiate reward memory switch within the BLA→NA shell circuit that controls opiate reward magnitude as a function of opiate exposure state.
外侧杏仁核（BLA）、腹侧被盖区和伏隔核（NAc）形成一个功能连接的神经网络，参与阿片类药物相关奖赏和记忆的处理。腹侧被盖区到 BLA 的多巴胺（DA）投射调节 BLA 内的联想性可塑性机制。然而，DA 受体信号在 BLA 中的作用及其对阿片类奖赏处理过程中向 NAc 的功能输出目前尚不清楚。我们使用一种无偏的位置条件反射程序，在阿片类药物-naive 或阿片类药物依赖/戒断大鼠的 BLA 内微输注特定的 DA D1 或 D2 受体激动剂后，测量吗啡的奖赏效应。BLA 内 D1 受体的激活强烈增强了阿片类药物的行为奖赏效应，仅在阿片类药物-naive 状态下。然而，一旦出现阿片类药物依赖和戒断，BLA 内 DA 介导的阿片类药物奖赏凸显的增强作用转变为 D2 受体依赖性底物。我们接下来在 NAc 壳（NA 壳）中进行了单细胞、活体细胞外神经元记录，以确定 BLA 内 D1/D2 受体的激活是否可以调节 NA 壳神经元对吗啡的反应模式。与我们的行为结果一致，BLA 内 D1 或 D2 受体的激活增强了 NAc“壳”（NA 壳）神经元对亚奖赏阈值阿片类药物给药的反应，这与阿片类药物-naive 和阿片类药物依赖/戒断状态之间的相同功能边界一致。最后，NA 壳内 N-甲基-D-天冬氨酸传递的阻断阻断了 BLA 内 DA D1 或 D2 受体介导的阿片类药物奖赏增强作用。我们的研究结果表明，外侧杏仁核（BLA）→NA 壳回路中的新型和功能性 DA D1/D2 受体介导的阿片类药物奖赏记忆开关控制阿片类药物奖赏的大小，作为阿片类药物暴露状态的函数。
