Rac1信号通路在小鼠可卡因情景线索记忆过程中的作用

目的:探讨Rac1信号通路在小鼠可卡因情景线索记忆过程中的作用。方法:将成年雄性C57BL/6J小鼠随机分为对照组(control)、可卡因配对的条件性位置偏爱组(CPP)和Rac1抑制剂NSC23766处理组(NSC),利用CPP实验检测可卡因是否可诱导小鼠产生CPP,利用立体定位技术注射AAV-GFP病毒于小鼠海马CA1区并做免疫荧光染色观察海马CA1区神经元的形态;利用Western Blot及GST-pull down方式检测蛋白表达及活性变化;采用Rac1抑制剂NSC23766阻断信号通路探讨其对小鼠可卡因诱导的CPP的影响。结果:可卡因可以诱导小鼠形成CPP,并导致Rac1 GTPase活性增强及其下游信号分子cofilin磷酸化活性升高,并最终导致海马CA1区锥体神经元发生神经可塑性变化。结论:Rac1信号通路通过影响小鼠海马CA1区锥体神经元发生结构可塑性,从而参与调控可卡因情景线索记忆。

Rac1 signaling pathway is involved in cocaine-associated mouse contextual memory

Objective:To investigate whether the Rac1 signaling pathway is involved in the regulation of cocaine-associated contextual memory in mice.Methods:Adult male C57BL/6 J mice were randomly divided into the control group,cocaine-paired conditioned place preference(CPP)group,and another group treated with Rac1 inhibitor NSC23766(NSC).The CPP experiment was used to detect whether cocaine can induce conditioned place preference in mice;The morphology of the neurons was detected by immunofluorescence staining after transfected the AAV-GFP virus into hippocampal CA1 neurons by stereotactic technology;Western Blot or GST-pull down techniques were carried out to detect protein expression;Rac1 inhibitor NSC23766 block the Rac1 signaling pathway in order to seek its effect on cocaine-induced CPP in mice.Results:Cocaine can induce CPP in mice,meanwhile,Rac1 GTPase activity and the phosphorylation of cofilin were enhanced,eventually led to neuroplasticity changes on pyramidal neurons in the hippocampal CA1 region.Conclusion:The Rac1 signaling pathway induced cocaine CPP by affecting the neuroplasticity in the hippocampal CA1 region.