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Effect of glycine site/NMDA receptor antagonist MRZ2/576 on the conditioned place preference and locomotor activity induced by morphine in mice
Authors:Yong-ping Zhu  Zai-hao Long  Ming-lan Zheng  Ralf Binsack
Institution:(1) Department of Toxicology, School of Medicine, Zhejiang University, Hangzhou, 310006, China;(2) Technology Center of Ningbo Entry-Exit Inspection and Quarantine Bureau, Ningbo, 315012, China;(3) Zhejiang Center for Disease Prevention and Control, Hangzhou, 310009, China
Abstract:Objective: To study the effect of glycine site/NMDA (N-methyl-D-aspartate) receptor antagonist MRZ2/576 on the conditioned place preference (CPP) and locomotor activity induced by morphine in mice. Methods: Different doses (1.25, 2.5 and 5 mg/kg, i.p.) of MRZ2/576 were used to evaluate the effect of MRZ2/576 on the acquisition and expression of CPP induced by morphine (5 mg/kg) in mice. In addition, we examined the locomotor activity of mice in conditioning and testing phase of CPP paradigm. Results: MRZ2/576 alone could not establish place preference, but a 5 mg/kg dose of MRZ2/576 could block both acquisition and expression of morphine-induced CPP. In testing phase of CPP, there was no statistical difference for locomotor activity between the groups; injection of MRZ2/576 showed a dose-dependent decrease of locomotor activity on both control and morphine-treated mice, especially 5 mg/kg of MRZ2/576 significantly suppressed the locomotor activity of mice. Conclusion: Based on the present results, we assume that MRZ2/576 can antagonize the rewarding effect of morphine, suggesting that this glycine site/NMDA receptor antagonist could be used to treat addictions due to its light side effect profile.
Keywords:Morphine  MRZ2/576  NMDA receptor  Glycine site  Conditioned place
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