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Involvement of AMPA/Kainate Glutamate Receptor in the Extinction and Reinstatement of Morphine-Induced Conditioned Place Preference: A Behavioral and Molecular Study

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Abstract

Glutamate receptors in mesolimbic areas such as the nucleus accumbens, ventral tegmental area, prefrontal cortex (PFC), and hippocampus (HIP) are a component of the mechanisms of drug-induced reward and can modulate the firing pattern of dopaminergic neurons in the reward system. In addition, several lines of study have indicated that cAMP response element-binding protein (CREB) and c-fos have important role in morphine-induced conditioned place preference (CPP) induced by drugs of abuse, such as morphine, cocaine, nicotine, and alcohol. Therefore, in the present study, we investigated the changes in phosphorylated CREB (p-CREB) and c-fos induction within the nucleus accumbens (NAc), HIP, and PFC after intracerebroventricular (ICV) administration of different doses of CNQX or vehicle during extinction period or reinstatement of morphine-induced CPP. In all groups, the CPP procedure was done; afterward, the conditioning scores were recorded by Ethovision software. After behavioral test recording, we dissected out the NAc, HIP, and PFC regions and measured the p-CREB/CREB ratio and c-fos level by Western blot analysis. Our results showed that administration of CNQX significantly shortened the extinction of morphine CPP. Besides, ICV microinjection of CNQX following extinction period decreased the reinstatement of morphine CPP in extinguished rats. In molecular section, in treatment group, all mentioned factors were dose-dependently decreased in comparison with vehicle group (DMSO) after ICV microinjection of different doses of CNQX but not in pre-extinction microinjection. These findings suggested that antagonism of AMPA receptor decreased p-CREB/CREB ratio and c-fos level in the PFC, NAc, and HIP. Modulation of the drug memory reconsolidation may be useful for faster extinction of drug-induced reward and attenuation of drug-seeking behavior.

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Acknowledgments

This study was carried out as part of a PhD student thesis project in Shahid Beheshti University of Medical Sciences. This work was supported by the Grant (No. 1392-1-103-1140) from Neurophysiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Mazandaran University of Medical Sciences, Ramsar International Branch, Sari, Iran

    Ali Siahposht-Khachaki

  2. Neurophysiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Zahra Fatahi

  3. Neurobiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Asal Yans & Fariba Khodagholi

  4. Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran

    Abbas Haghparast

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  1. Ali Siahposht-Khachaki
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Correspondence to Abbas Haghparast.

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Siahposht-Khachaki, A., Fatahi, Z., Yans, A. et al. Involvement of AMPA/Kainate Glutamate Receptor in the Extinction and Reinstatement of Morphine-Induced Conditioned Place Preference: A Behavioral and Molecular Study. Cell Mol Neurobiol 37, 315–328 (2017). https://doi.org/10.1007/s10571-016-0371-2

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