Department of Pharmacology and the Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, United States.
Brain Res Bull. 2010 May 31;82(3-4):184-7. doi: 10.1016/j.brainresbull.2010.03.005. Epub 2010 Mar 25.
Recent evidence suggests a critical role for the intracellular signaling protein glycogen synthase kinase-3 (GSK3) in hyperactivity associated with dopaminergic transmission. Here, we investigated whether activation of GSK3 is necessary for the expression of behaviors specifically produced by dopamine D1 receptor activation. To assess the role of GSK3 in dopamine D1 receptor-induced hyperactivity, mice were pretreated with the selective GSK3 inhibitor SB 216763 (0.25-7.5mg/kg, i.p.) or its vehicle prior to administration of the dopamine D1 receptor full-agonist SKF-82958 (1.0mg/kg, i.p.) or saline control. Inhibition of GSK3 via SB 216763 dose-dependently reduced ambulatory and stereotypic activity produced by SKF-82958. These data implicate a role for GSK3 in the behavioral manifestations associated with dopamine D1 receptor activation.
最近的证据表明，细胞内信号蛋白糖原合酶激酶-3（GSK3）在与多巴胺能传递相关的过度活跃中起着关键作用。在这里，我们研究了 GSK3 的激活是否是多巴胺 D1 受体激活所产生的行为表达所必需的。为了评估 GSK3 在多巴胺 D1 受体诱导的过度活跃中的作用，在给予多巴胺 D1 受体完全激动剂 SKF-82958（1.0mg/kg，ip）或生理盐水对照之前，用选择性 GSK3 抑制剂 SB 216763（0.25-7.5mg/kg，ip）或其载体预处理小鼠。通过 SB 216763 抑制 GSK3 剂量依赖性地减少了由 SKF-82958 引起的走动和刻板行为。这些数据表明 GSK3 在与多巴胺 D1 受体激活相关的行为表现中起作用。
