Dept. of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239-3098, USA.
Behav Brain Res. 2011 Mar 1;217(2):399-407. doi: 10.1016/j.bbr.2010.11.018. Epub 2010 Nov 11.
Although extracellular signal-regulated kinase (ERK) activity is essential for the acquisition of a variety of associative learning tasks, its involvement in the acquisition and extinction of ethanol (EtOH)-induced conditioned place preference (CPP) remains unknown. Therefore, in these experiments we examined the effects of the ERK-kinase (MEK)-inhibitor SL327 on acquisition and expression of EtOH-CPP as well as the dose- and time-dependent effects of SL327 on CPP extinction. The parametric findings of Experiment 1 showed that three 30-min (but not 15- or 5-min) non-reinforced trials were required to completely extinguish EtOH-CPP in male, DBA/2J mice. In Experiments 2 and 3, SL327 (30 and 50mg/kg), administered 30 or 90min prior to extinction trials, was unable to impair EtOH-CPP extinction. Experiment 4 showed that SL327 (50mg/kg) had no effect on acquisition of EtOH-CPP or the development of EtOH-induced sensitization during conditioning. When administered prior to testing in Experiments 5 and 6, SL327 did not alter expression of EtOH-CPP but did reduce test activity. Importantly, SL327 significantly reduced pERK protein levels when assessed in the dorsal striatum and motor cortex (Experiment 7). Together, these data suggest that EtOH-related learning and EtOH reward in mice, as assessed with CPP, are not impaired by the systemically administered MEK-inhibitor SL327.
尽管细胞外信号调节激酶（ERK）的活性对于获得各种联想学习任务是必不可少的，但它在乙醇（EtOH）诱导的条件性位置偏好（CPP）的获得和消退中的作用尚不清楚。因此，在这些实验中，我们研究了 ERK-激酶（MEK）抑制剂 SL327 对 EtOH-CPP 的获得和表达的影响，以及 SL327 对 CPP 消退的剂量和时间依赖性影响。实验 1 的参数发现表明，雄性 DBA/2J 小鼠需要进行三次 30 分钟（而不是 15 分钟或 5 分钟）的非强化试验才能完全消除 EtOH-CPP。在实验 2 和 3 中，在消退试验前 30 或 90 分钟给予 SL327（30 和 50mg/kg），无法损害 EtOH-CPP 的消退。实验 4 表明，SL327（50mg/kg）对 EtOH-CPP 的获得或在条件作用期间 EtOH 诱导的敏化的发展没有影响。在实验 5 和 6 中，在测试前给予 SL327 时，它不会改变 EtOH-CPP 的表达，但会减少测试活动。重要的是，SL327 显著降低了在背侧纹状体和运动皮层中评估的 pERK 蛋白水平（实验 7）。综上所述，这些数据表明，用 CPP 评估的小鼠与乙醇相关的学习和乙醇奖励不受系统给予的 MEK 抑制剂 SL327 的损害。
