人和非人灵长类动物的背纹状体由尾状核和壳核组成。这两个区域接收不同的皮质投影并且在功能上是不同的。尾状参与目标导向行为的控制,而壳核与习惯的学习和形成有关。以前的报道表明,乙醇对这两个区域的神经传递有不同的影响。因为神经递质主要通过G蛋白偶联受体(GPCRs)发出信号来调节神经元活动,本研究旨在确定乙醇是否对参与GPCRs运输和功能的蛋白质的表达具有区域依赖性影响,包括G蛋白亚基及其效应子,蛋白激酶,和细胞骨架的元素。进行蛋白质印迹以检查在自由进入条件下自我施用乙醇1年的雄性食蟹猴的尾状核和壳核中的蛋白质水平,以及在相同操作条件下自行施用等热量甜味溶液的对照动物。在研究的18种蛋白质中,我们发现一种蛋白质(PKCβ)的水平升高,和13种蛋白质(Gαi1/3,Gαi2,Gαo,Gβ1γ,PKCα,PKCε,CaMKII,GSK3β,β-肌动蛋白,cofilin,α-微管蛋白,和微管蛋白聚合促进蛋白)在饮酒猕猴的尾状中减少。然而,乙醇不会改变壳核中任何蛋白质的表达。这些观察结果强调了尾状核对慢性乙醇暴露引起的蛋白质表达变化的独特脆弱性。这些改变是否与乙醇诱导的GPCR功能和神经传递失调有关,值得进一步研究。
The dorsal striatum is composed of the caudate nucleus and the putamen in human and non-human primates. These two regions receive different cortical projections and are functionally distinct. The caudate is involved in the control of goal-directed behaviors, while the putamen is implicated in habit learning and formation. Previous reports indicate that ethanol differentially influences neurotransmission in these two regions. Because neurotransmitters primarily signal through G protein-coupled receptors (GPCRs) to modulate neuronal activity, the present study aimed to determine whether ethanol had a region-dependent impact on the expression of proteins that are involved in the trafficking and function of GPCRs, including G protein subunits and their effectors, protein kinases, and elements of the cytoskeleton. Western blotting was performed to examine protein levels in the caudate and the putamen of male cynomolgus macaques that self-administered ethanol for 1 year under free access conditions, along with control animals that self-administered an isocaloric sweetened solution under identical operant conditions. Among the 18 proteins studied, we found that the levels of one protein (PKCβ) were increased, and 13 proteins (Gαi1/3, Gαi2, Gαo, Gβ1γ, PKCα, PKCε, CaMKII, GSK3β, β-actin, cofilin, α-tubulin, and tubulin polymerization promoting protein) were reduced in the caudate of alcohol-drinking macaques. However, ethanol did not alter the expression of any proteins examined in the putamen. These observations underscore the unique vulnerability of the caudate nucleus to changes in protein expression induced by chronic ethanol exposure. Whether these alterations are associated with ethanol-induced dysregulation of GPCR function and neurotransmission warrants future investigation.