Post-training cocaine exposure facilitates spatial memory consolidation in C57BL/6 mice.

Post-training cocaine exposure facilitates spatial memory consolidation in C57BL/6 mice.
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DOI:
10.1002/hipo.20941
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发表时间:
2012-04
期刊:
影响因子:
3.5
通讯作者:
Crawford, Cynthia A.
Crawford, Cynthia A.
中科院分区:
医学3区
文献类型:
--
作者:
Iniguez, Sergio D.;Charntikov, Sergios;Baella, Shelley A.;Herbert, Matthew S.;Bolanos-Guzman, Carlos A.;Crawford, Cynthia A.

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在本研究中,我们使用Morris水迷宫(MWM)检查了训练后注射可卡因促进空间记忆表现的能力。我们还研究了海马蛋白激酶A(PKA)和细胞外信号调节激酶1/2(ERK)信号转导可能在可卡因介导的空间记忆巩固过程中发挥的作用。雄性和雌性C57 BL/6小鼠首先在MWM任务中训练(8次连续试验),然后注射可卡因(0、1.25、2.5、5或20 mg/kg),并在24小时延迟后重新测试平台位置的记忆。可卡因对空间记忆表现具有剂量依赖性影响,因为只有接受2.5 mg/kg可卡因的小鼠显示出定位平台的潜伏期显著减少。MWM性能没有性别差异,但是,女性表现出较高的海马PKA水平相比,男性。第二个实验表明,2.5毫克/公斤可卡因增强MWM性能只有在2小时内,但不是4小时后,空间训练。我们还发现,可卡因(2.5 mg/kg)增加海马内的ERK 2磷酸化及其下游靶点之一(核糖体S6激酶),这一机制可能是负责的,至少部分,可卡因介导的空间记忆性能增强。总体而言,这些数据表明,在训练后2小时内给予低剂量的可卡因(2.5 mg/kg)有助于C57 BL/6小鼠的MWM空间记忆表现。
In the present study, we examined the ability of post-training injections of cocaine to facilitate spatial memory performance using the Morris water maze (MWM). We also investigated the role that hippocampal protein kinase A (PKA) and extracellular signal-regulated kinase 1/2 (ERK) signaling may play in cocaine-mediated spatial memory consolidation processes. Male and female C57BL/6 mice were first trained in a MWM task (eight consecutive trials) then injected with cocaine (0, 1.25, 2.5, 5, or 20 mg/kg), and memory for the platform location was retested after a 24 hr delay. Cocaine had a dose-dependent effect on spatial memory performance because only the mice receiving 2.5 mg/kg cocaine displayed a significant reduction in latency to locate the platform. No sex differences in MWM performance were observed; however, females showed higher hippocampal levels of PKA when compared to males. A second experiment demonstrated that 2.5 mg/kg cocaine enhanced MWM performance only when administered within 2, but not 4 hr after spatial training. We also found that cocaine (2.5 mg/kg) increased ERK2 phosphorylation within the hippocampus and one of its downstream targets (ribosomal S6 kinase), a mechanism that may be responsible, at least in part, for the enhanced cocaine-mediated spatial memory performance. Overall, these data demonstrate that a low dose of cocaine (2.5 mg/kg) administered within 2-hr after training facilitates MWM spatial memory performance in C57BL/6 mice.
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