Department of Physiology and Pharmacology, Mazandaran University of Medical Sciences, Ramsar International Branch, Sari, Iran.
Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neurosci Lett. 2018 Jan 1;662:147-151. doi: 10.1016/j.neulet.2017.10.028. Epub 2017 Oct 17.
Neural circuitry comprising the ventral tegmental area, nucleus accumbens (NAc), prefrontal cortex (PFC) and hippocampus (HIP) has a main role in reward phenomena. Previous behavioral studies indicated that intracerebroventricular administration of AP5 (NMDA glutamate receptor antagonist) and CNQX (AMPA/kainate glutamate receptor antagonist) during the extinction and before reinstatement of morphine-induced conditioned place preference (CPP) reduced the extinction period and reinstatement of morphine-CPP. Therefore, in the present study, we tried to evaluate the effect of antagonism of NMDA glutamate receptors on the p-CREB/CREB ratio and c-fos expression in the NAc, PFC and HIP during these two phases of morphine-CPP in male adult albino Wistar rats. The p-CREB/CREB ratio and c-fos levels were estimated by Western blot analysis. The results revealed that these two factors decreased by antagonism of NMDA glutamate receptors (different doses of AP5) compared to saline-control group in aforementioned regions. The reduction of molecular markers, especially the p-CREB/CREB ratio, after AP5 administration was more during the extinction period. Therefore, it can be assumed that consolidation and reconsolidation of morphine memory via intra-PFC, -NAc and -HIP NMDA glutamate receptors are in accordance with changes in p-CREB/CREB ratio and c-fos levels.
腹侧被盖区、伏隔核（NAc）、前额叶皮层（PFC）和海马（HIP）组成的神经回路在奖励现象中起主要作用。以前的行为研究表明，在消退期间和吗啡诱导的条件性位置偏爱（CPP）的复燃前，向脑室内给予 AP5（NMDA 谷氨酸受体拮抗剂）和 CNQX（AMPA/kainate 谷氨酸受体拮抗剂），可减少消退期和吗啡-CPP 的复燃。因此，在本研究中，我们试图评估 NMDA 谷氨酸受体拮抗剂在雄性成年白化 Wistar 大鼠吗啡-CPP 的这两个阶段对 NAc、PFC 和 HIP 中 p-CREB/CREB 比值和 c-fos 表达的影响。通过 Western blot 分析来评估 p-CREB/CREB 比值和 c-fos 水平。结果表明，与生理盐水对照组相比，NMDA 谷氨酸受体拮抗剂（不同剂量的 AP5）在上述区域降低了这两个因素。在消退期，AP5 给药后分子标志物，尤其是 p-CREB/CREB 比值的减少更为明显。因此，可以假设通过 PFC、NAc 和 HIP 中的 NMDA 谷氨酸受体对吗啡记忆的巩固和再巩固与 p-CREB/CREB 比值和 c-fos 水平的变化一致。
