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The Activation of NMDA Receptor–ERK Pathway in the Central Amygdala is Required for the Expression of Morphine-Conditioned Place Preference in the Rat

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Abstract

Reinforcing effects of addictive drugs can be evaluated with the conditioned place preference (CPP) test which involves both the action of drugs and environmental cues. However, the encoded neural circuits and underlying signaling mechanism are not fully understood. In this study, we have used morphine-CPP model in the rat and characterized the role of N-methyl-d-aspartate (NMDA) receptor and the phosphorylation of extracellular signal-regulated kinase (ERK) in the central nuclei of amygdala (CeA) in the expression of morphine-induced CPP. We have found that morphine repeated pairing treatment causes a significant preference for compartment paired with morphine after 1 day or 7 days post-training, which is associated with increased ERK1/2 phosphorylation (p-ERK1/2, a measure of ERK activity) in the CeA. More than 80% of the positive p-ERK1/2 neurons express NMDA receptor subunit NR1 by double immunofluorescence studies. The infusion of either MEK inhibitor U0126 or NMDA receptor antagonist MK-801 in the CeA not only suppresses the activation of ERK1/2 in the CeA but also abolishes the expression of CPP. These results suggest that the activation of the NMDA receptor–ERK signaling pathway in the CeA is required for the expression of morphine-induced place preference in the rat.

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Abbreviations

CeA:

Central amygdala

CPP:

Conditioned place preference

CPA:

Conditioned place aversion

ERK:

Extracellular signal-regulated kinase

NMDA:

N-Methyl-d-aspartate

NR1:

N-Methyl-d-aspartate receptor 1

p-ERK:

Phosphorylation of ERK

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Acknowledgments

This study was supported by National Natural Science Foundation of China (30971533 to C.Q.L., 30971050 to W.H) and National Key Basic Research and Development Program (NKBRDP) of China (2009CB522000) to W.H.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, 172 Tongzhipo Road, Changsha, 410013, Hunan, China

    Fang Li, Xiao-Sheng Wang, Jian-Yi Zhang & Chang-Qi Li

  2. Department of Anesthesia, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China

    Ru-Ping Dai

  3. Department of Human Physiology and Center for Neuroscience, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia

    Xin-Fu Zhou

  4. Mental Health Institute, The Second Xiangya Hospital of Central South University, 139 Renmin (M) Road, Changsha, 410011, Hunan, China

    Wei Hao

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  1. Fang Li
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  2. Xiao-Sheng Wang
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  3. Ru-Ping Dai
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  4. Jian-Yi Zhang
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  5. Xin-Fu Zhou
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Corresponding authors

Correspondence to Wei Hao or Chang-Qi Li.

Additional information

Fang Li and Xiao-Sheng Wang contributed equally to this work.

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Li, F., Wang, XS., Dai, RP. et al. The Activation of NMDA Receptor–ERK Pathway in the Central Amygdala is Required for the Expression of Morphine-Conditioned Place Preference in the Rat. Neurotox Res 20, 362–371 (2011). https://doi.org/10.1007/s12640-011-9250-2

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  • DOI: https://doi.org/10.1007/s12640-011-9250-2

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