Methamphetamine-induced short-term increase and long-term decrease in spatial working memory affects protein Kinase M zeta (PKMζ), dopamine, and glutamate receptors.
Methamphetamine-induced short-term increase and long-term decrease in spatial working memory affects protein Kinase M zeta (PKMζ), dopamine, and glutamate receptors.
复制标题
DOI：
10.3389/fnbeh.2014.00438
复制
发表时间：
2014
影响因子：
3
通讯作者：
Serrano PA
中科院分区：
文献类型：
--
作者：
Braren SH;Drapala D;Tulloch IK;Serrano PA
甲基苯丙胺（MA）是一种有毒的成瘾性药物，可调节学习和记忆，但其神经机制尚未完全了解。我们研究了2周注射MA（30 mg/kg）对工作记忆的影响，使用径向8臂迷宫（RAM）在5周内在同龄小鼠中进行。与盐水注射对照相比，MA处理的小鼠在第一次MA注射后1周显示出工作记忆表现的显著改善。在5周的MA戒断之后，在RAM的参考和工作记忆版本上重新训练小鼠以评估认知灵活性。MA处理的小鼠显示出显著更多的工作记忆错误，而对参考记忆表现没有影响。评估海马和背侧纹状体谷氨酸受体亚单位GluA 2和GluN 2B的表达;多巴胺标记物多巴胺1受体（D1）、多巴胺转运蛋白（DAT）和酪氨酸羟化酶（TH）;以及记忆标记物蛋白激酶M ζ（PKMζ）和蛋白激酶C ζ（PKCζ）。在海马内，PKM β 2和GluA 2在MA后均显著降低，这支持了较差的记忆表现。此外，GluN 2B的显著增加和D1的减少鉴定了突触功能失调。在纹状体中，MA治疗增加了与多巴胺功能亢进相关的细胞溶质DAT和TH水平。MA处理显著降低GluN 2B，同时增加纹状体内的PKM β和PKC β。我们讨论了MA治疗后PKM β/PKC β在调节多巴胺和谷氨酸受体中的潜在作用。这些结果确定了潜在的潜在机制，工作记忆缺陷引起的MA。
Methamphetamine (MA) is a toxic, addictive drug shown to modulate learning and memory, yet the neural mechanisms are not fully understood. We investigated the effects of 2 weekly injections of MA (30 mg/kg) on working memory using the radial 8-arm maze (RAM) across 5 weeks in adolescent-age mice. MA-treated mice show a significant improvement in working memory performance 1 week following the first MA injection compared to saline-injected controls. Following 5 weeks of MA abstinence mice were re-trained on a reference and working memory version of the RAM to assess cognitive flexibility. MA-treated mice show significantly more working memory errors without effects on reference memory performance. The hippocampus and dorsal striatum were assessed for expression of glutamate receptors subunits, GluA2 and GluN2B; dopamine markers, dopamine 1 receptor (D1), dopamine transporter (DAT) and tyrosine hydroxylase (TH); and memory markers, protein kinase M zeta (PKMζ) and protein kinase C zeta (PKCζ). Within the hippocampus, PKMζ and GluA2 are both significantly reduced after MA supporting the poor memory performance. Additionally, a significant increase in GluN2B and decrease in D1 identifies dysregulated synaptic function. In the striatum, MA treatment increased cytosolic DAT and TH levels associated with dopamine hyperfunction. MA treatment significantly reduced GluN2B while increasing both PKMζ and PKCζ within the striatum. We discuss the potential role of PKMζ/PKCζ in modulating dopamine and glutamate receptors after MA treatment. These results identify potential underlying mechanisms for working memory deficits induced by MA.
登录
查看更多内容
影响因子：
4.4
作者：
Casaletto, K. B.;Obermeit, L.;Morgan, E. E.;Weber, E.;Franklin, D. R.;Grant, I.;Woods, S. P.
通讯作者：
Woods, S. P.
影响因子：
2.3
作者：
Bowyer, John F.;Ali, Syed
通讯作者：
Ali, Syed
影响因子：
7.6
作者：
Belcher, AM;O'Dell, SJ;Marshall, JF
通讯作者：
Marshall, JF
影响因子：
7.6
作者：
Belcher, Annabelle M.;Feinstein, Erin M.;Marshall, John F.
通讯作者：
Marshall, John F.
影响因子：
4.8
作者：
Fiorentini, C;Gardoni, F;Missale, C
通讯作者：
Missale, C