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.
机构:[1]School of Traditional Chinese Medicine, Southern Medical University,[2]Department of Pharmacy, Guangdong Provincial Corps Hospital of Chinese People’s Armed Police Forces,[3]Department of Pathophysiology, Guangdong Province Key Laboratory of Functional Proteomics, Southern Medical University, Guangzhou,[4]Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
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.
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.
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.
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.
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.
P-CREB, Nurr1 and BDNF play an important role in the formation of ketamine-induced place preference in ratsRhynchophylline reversed the expression of p-CREB, Nurr1 and BDNF which was activated by ketamine in the hippocampusRhynchophylline demonstrates the potential effect of mediates ketamine induced rewarding effect. 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.
基金:
This work was supported by the National Natural Science Foundation
of China (No. 81229003, 81673628); the Guangzhou Major Science and
Technology Project (No. 20Foundation of Guangdong Province, China
(No. 2014A030310251).1300000050); and the Natural Science.
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外文
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最新[2025]版:
大类|4 区医学
小类|4 区药物化学
第一作者:
第一作者机构:[1]School of Traditional Chinese Medicine, Southern Medical University,[2]Department of Pharmacy, Guangdong Provincial Corps Hospital of Chinese People’s Armed Police Forces,
共同第一作者:
通讯作者:
通讯机构:[1]School of Traditional Chinese Medicine, Southern Medical University,[4]Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China[*1]Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.[*2]School of Traditional Chinese Medicine, Southern Medical University, 1063 Shatai Road, Guangzhou, 510 515, China.
推荐引用方式(GB/T 7714):
Guo Youli,Luo Chaohua,Tu Genghong,et al.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.[J].Pharmacognosy magazine.14(53):81-86.doi:10.4103/pm.pm_90_17.
APA:
Guo Youli,Luo Chaohua,Tu Genghong,Li Chan,Liu Yi...&Mo Zhixian.(0).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..Pharmacognosy magazine,14,(53)
MLA:
Guo Youli,et al."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.".Pharmacognosy magazine 14..53(0):81-86