Ethanol-Induced Extracellular Signal Regulated Kinase: Role of Dopamine D1 Receptors
Ethanol-Induced Extracellular Signal Regulated Kinase: Role of Dopamine D1 Receptors
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DOI：
10.1111/j.1530-0277.2009.00907.x
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发表时间：
2009-05-01
影响因子：
3.2
通讯作者：
Acquas, Elio
中科院分区：
文献类型：
--
作者：
Ibba, Federico;Vinci, Stefania;Acquas, Elio
成瘾药物会激活与其情感和动机特性密切相关的大脑区域中的细胞外信号调节激酶（ERK）。本研究的目的是证明乙醇诱导的伏隔核 (Acb) 和扩展杏仁核 [终纹床核 (BSTL) 和杏仁核中央核 (CeA)] 中的 ERK 激活，并强调多巴胺 (DA) D-1 受体在这些效应中的作用。通过灌胃和 ERK 磷酸化给予乙醇（0.5、1 和 2 g/kg）通过免疫组织化学在细胞核 Acb（壳和核）、BSTL 和 CeA 中测定。在乙醇 (1 g/kg) 前 10 分钟给予 DA D-1 受体拮抗剂 SCH 39166 (SCH) (50 μg/kg)。定量显微镜检查表明，乙醇剂量依赖性地增加细胞核 Acb、BSTL 和 CeA 的壳和核中的磷酸化 ERK 免疫反应性（光学和神经元密度）。 SCH 预处理完全阻止了乙醇 (1 g/kg) 在所有研究的大脑区域引起的增加。这项研究的结果表明，与其他成瘾药物类似，乙醇通过 DA D-1 受体介导的机制激活 Acb 核中的 ERK 并扩展杏仁核。总体而言，这些结果表明 D-1 受体/ERK 通路可能在乙醇的激励特性中发挥关键作用。
Addictive drugs activate extracellular signal regulated kinase (ERK) in brain regions critically involved in their affective and motivational properties. The aim of this study was to demonstrate the ethanol-induced activation of ERK in the nucleus accumbens (Acb) and in the extended amygdala [bed nucleus of the stria terminalis lateralis (BSTL) and central nucleus of the amygdala (CeA)] and to highlight the role of dopamine (DA) D-1 receptors in these effects.Ethanol (0.5, 1, and 2 g/kg) was administered by gavage and ERK phosphorylation was determined in the nucleus Acb (shell and core), BSTL, and CeA by immunohistochemistry. The DA D-1 receptor antagonist, SCH 39166 (SCH) (50 mu g/kg), was administered 10 minutes before ethanol (1 g/kg).Quantitative microscopic examination showed that ethanol, dose-dependently increased phospho-ERK immunoreactivity (optical and neuronal densities) in the shell and core of nucleus Acb, BSTL, and CeA. Pretreatment with SCH fully prevented the increases elicited by ethanol (1 g/kg) in all brain regions studied.The results of this study indicate that ethanol, similar to other addictive drugs, activates ERK in nucleus Acb and extended amygdala via a DA D-1 receptor-mediated mechanism. Overall, these results suggest that the D-1 receptors/ERK pathway may play a critical role in the motivational properties of ethanol.