D1R/PP2A/p-CaMKIIα signaling in the caudate putamen is involved in acute methamphetamine-induced hyperlocomotion
D1R/PP2A/p-CaMKIIα signaling in the caudate putamen is involved in acute methamphetamine-induced hyperlocomotion
复制标题
尾壳核中的 D1R/PP2A/p-CaMKIIα 信号传导参与急性甲基苯丙胺诱导的过度运动
DOI：
10.1016/j.neulet.2021.136102
复制
发表时间：
2021-07-10
影响因子：
2.5
通讯作者：
Liu，Xinshe
中科院分区：
文献类型：
--
作者：
Shang，Qing;Xiao，Jing;Liu，Xinshe
吸毒成瘾的突出表现是成瘾药物从试验性使用过渡到依赖性使用。急性使用甲基苯丙胺（METH）会引起一系列临床症状，包括过度运动。多巴胺D1受体（D1 R）介导的磷酸化钙/钙调蛋白依赖性蛋白激酶IIα（p-CaMKIIα，苏氨酸[Thr] 286）的负调节参与了单次METH给药诱导的急性效应。蛋白磷酸酶2A（PP 2A）是急性METH给药后连接D1 R和p-CaMKIIα（Thr 286）的潜在桥梁。然而，由单次METH给药诱导的过度运动的潜在机制仍不清楚。在这项研究中，SCH 23390（一种D1 R抑制剂）和LB 100（一种PP 2A抑制剂）的管理，以检查参与D1 R和PP 2A信号在急性甲硫氨酸诱导的小鼠运动过度。测量前额叶皮质（PFc）、中脑核（NAc）和尾壳核（CPu）中甲基化PP 2A-C（m-PP 2A-C，亮氨酸[Leu] 309）、磷酸化PP 2A-C（p-PP 2A-C，酪氨酸[Tyr] 307）、PP 2A-C、p-CaMKIIα（Thr 286）和CaMKIIα的蛋白水平。注射0.5 mg/kg SCH 23390可逆转急性MET诱导的CPu中m-PP 2A-C（Leu 309）蛋白水平升高和p-PP 2A-C（Tyr 307）蛋白水平降低，但在PFC和NAc中无此作用。此外，预先给予0.1 mg/kg LB 100可减弱单次METH给药诱导的过度运动，并逆转PFC、NAc和CPu中p-CaMKII（Thr 286）蛋白水平的降低。总之，这些结果表明，CPu中的D1 R/PP 2A/p-CaMKIIα信号级联可能参与单次给予METH后的过度运动。
Drug addiction is underscored by the transition from experimental use to dependent use of addictive drugs. Acute use of methamphetamine (METH) causes a range of clinical symptoms, including hyperlocomotion. Dopamine D1 receptor (D1R)-mediated negative regulation of phosphorylated calcium/calmodulin-dependent protein kinase IIα (p-CaMKIIα, threonine [Thr] 286) is involved in the acute effects induced by single METH administration. Protein phosphatase 2A (PP2A) is a potential bridge that links D1R and p-CaMKIIα (Thr 286) after acute METH administration. However, the mechanisms underlying hyperlocomotion induced by single METH administration remain unclear. In this study, SCH23390 (a D1R inhibitor) and LB100 (a PP2A inhibitor) were administered to examine the involvement of D1R and PP2A signaling in acute METH-induced hyperlocomotion in mice. The protein levels of methylated PP2A-C (m-PP2A-C, leucine [Leu] 309), phosphorylated PP2A-C (p-PP2A-C, tyrosine [Tyr] 307), PP2A-C, p-CaMKIIα (Thr 286), and CaMKIIα in the prefrontal cortex (PFc), nucleus accumbens (NAc), and caudate putamen (CPu) were measured. Administration of 0.5 mg/kg SCH23390 reversed the acute METH-induced increase in protein levels of m-PP2A-C (Leu 309) and the decrease in protein levels of p-PP2A-C (Tyr 307) in the CPu, but not in the PFC and NAc. Moreover, prior administration of 0.1 mg/kg LB100 attenuated hyperlocomotion induced by single METH administration and reversed the decrease in protein levels of p-CaMKII (Thr 286) in the PFC, NAc, and CPu. Collectively, these results indicate that the D1R/PP2A/p-CaMKIIα signaling cascade in the CPu may be involved in hyperlocomotion after a single administration of METH.