Effects of acute ethanol administration on methionine-enkephalin expression and release in regions of the rat brain
Effects of acute ethanol administration on methionine-enkephalin expression and release in regions of the rat brain
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DOI：
10.1016/j.npep.2010.05.001
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发表时间：
2010-10-01
期刊：
影响因子：
2.9
通讯作者：
Oikawa, J.
中科院分区：
文献类型：
--
作者：
Mendez, M.;Barbosa-Luna, I. G.;Oikawa, J.
多巴胺能中边缘系统在调节乙醇和其他滥用药物的增强特性中起关键作用。乙醇强化和高酒精饮酒行为被认为涉及乙醇诱导的内源性阿片系统的激活。乙醇可能在不同程度上改变阿片能的传递，包括阿片肽的生物合成和释放，以及与阿片受体的结合。研究不同剂量乙醇对大鼠伏隔核释放蛋氨酸-脑啡肽（Met-enk）的影响。研究了乙醇对NAcc、前额叶皮质（PFC）和尾壳核（CP）中Met-enk含量的影响。用微透析法研究Wistar麻醉大鼠的Met-enk释放，用放射免疫法测定肽浓度。乙醇经2小时基础释放期后腹腔注射给药。0.5、1和2.5 g/kg乙醇剂量诱导NAcc中Met-enk释放量增加2.7、4.9和3.4倍。然而，乙醇反应遵循不同的动力学，在最高的乙醇剂量下观察到最早的效应。相比之下，100 mM KCI产生的肽释放增加2.5倍。2.5 g/kg剂量的乙醇诱导NAcc中Met-enk含量显著降低66.7%，CP中肽水平显著降低76.4%，较低剂量的乙醇没有改变这些区域的Met-enk含量。另一方面，0.5 g/kg的乙醇剂量会导致pfc中Met-enk水平的不显著降低。我们的研究结果表明，乙醇诱导的中脑皮质边缘和黑质纹状体区域脑啡肽表达和释放的变化可能参与了乙醇中枢效应。乙醇释放的脑啡肽可能调节中边缘神经元的多巴胺能活性，在乙醇强化机制中起关键作用。(C) 2010 Elsevier Ltd.版权所有。
The dopaminergic mesolimbic system plays a key role in mediating the reinforcing properties of ethanol and other drugs of abuse. Ethanol reinforcement and high alcohol drinking behaviour have been suggested to involve the ethanol-induced activation of endogenous opioid systems. Ethanol may alter opioidergic transmission at different levels, including opioid peptide biosynthesis and release, as well as binding to opioid receptors. The aim of this work was to investigate the effects of different ethanol doses on methionine-enkephalin (Met-enk) release from the rat nucleus accumbens (NAcc). Ethanol effects were also studied on Met-enk content in the NAcc, prefrontal cortex (PFC) and caudate-putamen (CP). Met-enk release was studied by microdialysis in Wistar anesthetized rats and peptide concentrations were quantitated by radioimmunoassay. Ethanol was administered by intraperitoneal injection after a 2-h basal release period. Ethanol doses of 0.5, 1 and 2.5 g/kg induced a 2.7-, 4.9- and 3.4-fold increase in Met-enk release from the NAcc. However, ethanol responses followed different kinetics, with earliest effects observed with the highest ethanol dose. In comparison, a 2.5-fold increase in peptide release was produced by 100 mM KCI. Ethanol, at a dose of 2.5 g/kg, induced a significant 66.7% decrease in Met-enk content in the NAcc, as well as a 76.4% reduction in peptide levels in the CP. Lower ethanol doses did not alter Met-enk content in these regions. On the other hand, an ethanol dose of 0.5 g/kg produced a non-significant decrease in Met-enk levels in the PFC. Our results suggest that ethanol-induced changes in enkephalin expression and release in regions of the mesocorticolimbic and nigrostriatal pathways could be involved in ethanol central effects. Released enkephalins by ethanol may modulate the doparninergic activity of mesolimbic neurons and play a critical role in ethanol reinforcement mechanisms. (C) 2010 Elsevier Ltd. All rights reserved.