A sensitizing d-amphetamine regimen induces long-lasting spinophilin protein upregulation in the rat striatum and limbic forebrain
A sensitizing d-amphetamine regimen induces long-lasting spinophilin protein upregulation in the rat striatum and limbic forebrain
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DOI：
10.1111/j.1460-9568.2008.06481.x
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发表时间：
2008-11-01
影响因子：
3.4
通讯作者：
Marshall, John F.
中科院分区：
文献类型：
--
作者：
Boikess, Steven R.;Marshall, John F.
结构研究表明，长期服用精神兴奋剂会增加大鼠纹状体中树突棘的数量。本研究使用蛋白质印迹法和放射免疫细胞化学来检测精神兴奋剂诱导的嗜棘素水平的变化，嗜棘素是一种在树突棘中大量发现的蛋白质。在纹状体以及其他几个与精神兴奋剂诱导的神经可塑性有关的皮质下区域进行了Spinophilin测定。大鼠接受d-苯丙胺的递增（1-8 mg/kg）给药方案（每天两次，i. p.）持续5周，测试运动致敏性，并在28天后处死。发现该安非他明给药方案在这些动物中诱导显著的自发活动致敏。使用蛋白质印迹和放射免疫细胞化学，亲棘蛋白被发现在安非他明治疗的大鼠纹状体上调。此外，放射免疫细胞化学显示，在隔，海马，杏仁核和扣带回皮质，并在感觉运动皮质不变的spinophilin增加。因为它结合到F-肌动蛋白和蛋白磷酸酶-1，亲棘素已被提出作为一种蛋白质连接突触传递的变化，在脊柱的形态。放射免疫细胞化学的spinophilin提供了一种新的方法来识别大脑区域的神经元经历树突状变化后，慢性暴露于滥用药物。
Structural studies have shown that chronic regimens of psychostimulants increase dendritic spine number in the rat striatum. The present study used Western blotting and radioimmunocytochemistry to examine psychostimulant-induced changes in the levels of spinophilin, a protein found abundantly in dendritic spines. Spinophilin determinations were conducted in striatum as well as several other subcortical regions implicated in psychostimulant-induced neuroplasticity. Rats received an escalating (1-8 mg/kg) dosing regimen of d-amphetamine (twice daily, i.p.) for 5 weeks, were tested for locomotor sensitization, and were killed 28 days later. This amphetamine dosing regimen was found to induce a significant sensitization of locomotor activity in these animals. Using both Western blotting and radioimmunocytochemistry, spinophilin protein was found to be upregulated in the striatum of amphetamine-treated rats. In addition, radioimmunocytochemistry revealed that spinophilin was increased in the septum, hippocampus, amygdala and the cingulate cortex, and was unchanged in sensorimotor cortices. Because it binds to F-actin and protein phosphatase-1, spinophilin has been proposed as a protein linking synaptic transmission to changes in spine morphology. Radioimmunocytochemistry for spinophilin provides a novel approach to identification of brain regions whose neurons undergo dendritic change after chronic exposure to drugs of abuse.