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.
Keywords: Conditioned place preference; Hippocampus; NMDA glutamate receptor; Nucleus accumbens; Prefrontal cortex; Reward; c-fos; p-CREB/CREB ratio.
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