Drug addiction is a chronic recurrent brain disease characterized by compulsive drug use and a high tendency to relapse. We previously reported that the Ras-extracellular signal-regulated kinase (ERK)-ΔFosB pathway in the caudate putamen (CPu) was involved in methamphetamine-induced behavioral sensitization. Rap1, as an antagonist of Ras originally, was found to participate in neuronal synaptic plasticity recently, but the role of Rap1 in methamphetamine addiction is unclear. First, in this study, we constructed the acquisition, extinction and reinstatement of methamphetamine-induced conditioned place preference (CPP) in mice, respectively. Then, protein levels of Rap1, Ras and pERK/ERK in the prefrontal cortex (PFc), CPu and hippocampus of CPP mice on three phases were detected. We found that protein levels of Rap1, Ras and pERK/ERK in the CPu were significantly increased after repeated methamphetamine administration, as well as Rap1 and pERK/ERK in the hippocampus. However, protein levels of Rap1 and pERK/ERK in the CPu were decreased on the reinstatement of CPP mice. Therefore, Rap1 and Ras in the CPu and Rap1 in the hippocampus may participate in the regulation of the acquisition of methamphetamine-induced CPP in mice by activating ERK. Moreover, Rap1-ERK cascade in the CPu contributes to both the acquisition and reinstatement of methamphetamine-induced CPP in mice.

中文翻译：

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Rap1 和 Ras 的时空表达通过细胞外信号调节激酶激活介导甲基苯丙胺诱导的小鼠条件性位置偏好的获得和恢复。

药物成瘾是一种慢性复发性脑部疾病，其特征是强迫性药物使用和高复发倾向。我们之前曾报道尾状壳核 (CPu) 中的 Ras 细胞外信号调节激酶 (ERK)-ΔFosB 通路参与甲基苯丙胺诱导的行为致敏。Rap1 最初作为 Ras 的拮抗剂，最近被发现参与神经元突触可塑性，但 Rap1 在甲基苯丙胺成瘾中的作用尚不清楚。首先，在这项研究中，我们分别构建了甲基苯丙胺诱导的小鼠条件性位置偏好 (CPP) 的获得、灭绝和恢复。然后，分别检测三个时相CPP小鼠前额叶皮层（PFc）、CPu和海马区Rap1、Ras和pERK/ERK的蛋白水平。我们发现 Rap1 的蛋白质水平，重复施用甲基苯丙胺后，CPu 中的 Ras 和 pERK/ERK 显着增加，海马中的 Rap1 和 pERK/ERK 也显着增加。然而，在 CPP 小鼠恢复时，CPu 中 Rap1 和 pERK/ERK 的蛋白质水平降低。因此，CPu中的Rap1和Ras以及海马中的Rap1可能通过激活ERK参与调控甲基苯丙胺诱导的小鼠CPP的获得。此外，CPu 中的 Rap1-ERK 级联有助于甲基苯丙胺诱导的小鼠 CPP 的获得和恢复。CPu中的Rap1和Ras以及海马中的Rap1可能通过激活ERK参与调控甲基苯丙胺诱导的小鼠CPP的获得。此外，CPu 中的 Rap1-ERK 级联有助于甲基苯丙胺诱导的小鼠 CPP 的获得和恢复。CPu中的Rap1和Ras以及海马中的Rap1可能通过激活ERK参与调控甲基苯丙胺诱导的小鼠CPP的获得。此外，CPu 中的 Rap1-ERK 级联有助于甲基苯丙胺诱导的小鼠 CPP 的获得和恢复。