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

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.