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, Chaohua Luo2, Genghong Tu3, Chan Li2, Yi Liu2, Wei Liu2, Ken Kin Lam Yung4, Zhixian Mo2
1 School of Traditional Chinese Medicine, Southern Medical University; Department of Pharmacy, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou, China
2 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
3 Department of Pathophysiology, Guangdong Province Key Laboratory of Functional Proteomics, Southern Medical University, Guangzhou, China
4 Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
Ken Kin Lam Yung
Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong
School of Traditional Chinese Medicine, Southern Medical University, 1063 Shatai Road, Guangzhou, 510 515
Source of Support: None, Conflict of Interest: None
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.
Abbreviations used: Rhy: Rhynchophylline; CREB: cAMP response element binding protein; Nurr1: Nuclear receptor-related-1; BDNF: Brain-derived neurotrophic factor; CPP: Conditioned place preference; NMDA: N-methyl-D-aspartic acid; METH: Methamphetamine; CNS: Central nervous system; PFA: Paraformaldehyde; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; LTP: long-term potentiation.