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PM · Lens · Rhynchophylline Downregulates Phosphorylated cAMP Response Element Binding Protein, Nuclear Receptor-related-1, and Brain-derived Neurotrophic Factor Expression in the Hippocampus of Ketamine-induced Conditioned Place Preference Rats

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Article · Volume 14, Issue 53 · pp. 81–6

Rhynchophylline Downregulates Phosphorylated cAMP Response Element Binding Protein, Nuclear Receptor-related-1, and Brain-derived Neurotrophic Factor Expression in the Hippocampus of Ketamine-induced Conditioned Place Preference Rats

Youli Guo1,2, Chaohua Luo1, Genghong Tu3, Chan Li1, Yi Liu1, Wei Liu1, Ken Kin Lam Yung4, Zhixian Mo1

  1. 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
  2. 2Department of Pharmacy, Guangdong Provincial Corps Hospital of Chinese People’s Armed Police Forces, Guangzhou, China.
  3. 3Department of Pathophysiology, Guangdong Province Key Laboratory of Functional Proteomics, Southern Medical University, Guangzhou, China.
  4. 4Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.

Abstract

Background: Addiction to ketamine is becoming a serious public health issues, for which there exists no effective treatment. Rhynchophylline (Rhy) is an alkaloid extracted from certain Uncaria species that is well known for both its potent anti-addictive and neuroprotective properties. Increasing evidence supports the contributions of cAMP response element binding protein (CREB), nuclear receptor-related-1 (Nurr1), and brain-derived neurotrophic factor (BDNF) in modulating neural and behavioral plasticity which was induced by addictive drugs.Objective: To investigate the effects of Rhy on the behavior and the levels of phosphorylated CREB (p-CREB), Nurr1, and BDNF in the hippocampus of ketamine-induced conditioned place preference (CPP) rats.Materials and Methods: CPP paradigm was used to establish the model of ketamine-dependent rats and to evaluate the effect of Rhy on ketamine dependence. The expressions of p-CREB, Nurr1, and BDNF were tested by Western blotting and immunohistochemistry.Results: We observed that Rhy can reverse the behavior preference induced by ketamine CPP training. At the same time, expression of p-CREB, Nurr1, and BDNF, which was significantly increased by ketamine, was restored in the Rhy-treated group.Conclusion: This study indicates that Rhy can reverse the reward effect induced by ketamine in rats and the mechanism can probably be related to regulate the hippocampal protein expression of p-CREB, Nurr1, and BDNF.

Keywords: Brain-derived neurotrophic factor; conditioned place preference; ketamine; nuclear receptor-related-1; phosphorylated cAMP response element binding protein; rhynchophylline

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