PMID- 29576706 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220316 IS - 0973-1296 (Print) IS - 0976-4062 (Electronic) IS - 0973-1296 (Linking) VI - 14 IP - 53 DP - 2018 Jan-Mar TI - 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. PG - 81-86 LID - 10.4103/pm.pm_90_17 [doi] AB - 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. SUMMARY: 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. FAU - Guo, Youli AU - Guo Y AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. AD - Department of Pharmacy, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou, China. FAU - Luo, Chaohua AU - Luo C AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. FAU - Tu, Genghong AU - Tu G AD - Department of Pathophysiology, Guangdong Province Key Laboratory of Functional Proteomics, Southern Medical University, Guangzhou, China. FAU - Li, Chan AU - Li C AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. FAU - Liu, Yi AU - Liu Y AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. FAU - Liu, Wei AU - Liu W AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. FAU - Lam Yung, Ken Kin AU - Lam Yung KK AD - Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. FAU - Mo, Zhixian AU - Mo Z AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. LA - eng PT - Journal Article DEP - 20180220 PL - United States TA - Pharmacogn Mag JT - Pharmacognosy magazine JID - 101300403 PMC - PMC5858247 OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - conditioned place preference OT - ketamine OT - nuclear receptor-related-1 OT - phosphorylated cAMP response element binding protein OT - rhynchophylline COIS- There are no conflicts of interest. EDAT- 2018/03/27 06:00 MHDA- 2018/03/27 06:01 PMCR- 2018/01/01 CRDT- 2018/03/27 06:00 PHST- 2017/03/05 00:00 [received] PHST- 2017/03/31 00:00 [revised] PHST- 2018/03/27 06:00 [entrez] PHST- 2018/03/27 06:00 [pubmed] PHST- 2018/03/27 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - PM-14-81 [pii] AID - 10.4103/pm.pm_90_17 [doi] PST - ppublish SO - Pharmacogn Mag. 2018 Jan-Mar;14(53):81-86. doi: 10.4103/pm.pm_90_17. Epub 2018 Feb 20.