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Effects of Ifenprodil on Morphine-Induced Conditioned Place Preference and Spatial Learning and Memory in Rats

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Abstract

Drug addiction, as well as learning and memory, share common mechanisms in terms of neural circuits and intracellular signaling pathways. In the present study, the role of N-methyl-D-aspartate (NMDA) receptors, particularly those containing NR2B subunits, in morphine-induced conditioned place preference (CPP) and Morris water maze (MWM) learning and memory task was investigated. CPP was used as a paradigm for assessing the rewarding effect of morphine, and MWM was used to measure spatial learning and memory in male Sprague–Dawley rats. We found that ifenprodil, an antagonist highly selective for NR2B-containing NMDA receptors, dose-dependently blocked the development, maintenance and reinstatement of morphine-induced CPP, without evident impairment of the acquisition and retrieval of spatial memory in the MWM task. However, the consolidation of spatial memory was disrupted by a high dose (10 mg/kg) of ifenprodil. These results clearly demonstrate that NR2B-containing NMDA receptors are actively involved in addiction memory induced by morphine conditioning, but not in the acquisition and retrieval of spatial learning and memory. In conclusion, NR2B-containing NMDA receptors can be considered potential targets for the treatment of opiate addiction.

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Acknowledgments

This work was supported by a grant (30970933) from the National Natural Science Foundation, and the National Basic Research Program (2009CB522003) of China.

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  1. Neuroscience Research Institute, Department of Neurobiology, School of Basic Medical Sciences, Peking University, Key Lab for Neuroscience, The Ministry of Education, The Ministry of Public Health, 38 Xueyuan Road, 100083, Beijing, People’s Republic of China

    Yao-Ying Ma, Peng Yu, Chang-Yong Guo & Cai-Lian Cui

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  1. Yao-Ying Ma
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  2. Peng Yu
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Correspondence to Cai-Lian Cui.

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Ma, YY., Yu, P., Guo, CY. et al. Effects of Ifenprodil on Morphine-Induced Conditioned Place Preference and Spatial Learning and Memory in Rats. Neurochem Res 36, 383–391 (2011). https://doi.org/10.1007/s11064-010-0342-9

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