Departamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente. Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México DF, Mexico.
Neuropeptides. 2010 Feb;44(1):9-16. doi: 10.1016/j.npep.2009.11.009. Epub 2009 Dec 23.
The dopaminergic mesocorticolimbic system plays an important role in the reinforcing effects of ethanol. Opioid peptides modulate the activity of this system and have been suggested to mediate, at least in part, the reinforcing properties of ethanol. Thus, beta-endorphin (beta-END) could participate in the development of ethanol reinforcement and addiction. The aim of this work was to investigate the acute and chronic ethanol effects on beta-END content in regions of the mesolimbic system and to examine if chronic ethanol treatment alters ligand binding to mu opioid receptor (muOR). Male Wistar rats received a single acute ethanol dose of 2.5 g/kg or water by intra-gastric administration. For chronic ethanol treatment experiments, one group of rats was given ethanol (10% v/v solution) to drink, two groups were given equivalent volumes of sucrose (14.14% isocaloric solution) or water, respectively, and a fourth group had ad libitum access to food and water. Treatment was followed for 4 weeks. Beta-endorphin content in brain regions was quantified by radioimmunoassay and ligand binding studies to muOR were performed by quantitative autoradiography using 8 nM [(3)H]-DAMGO as radioligand. Acute ethanol decreased beta-END content in the hypothalamus (26%) 1h after administration. No ethanol effects were observed in the midbrain, ventral tegmental area, substantia nigra, nucleus accumbens, nucleus accumbens-septum and prefrontal cortex. Chronic ethanol treatment neither changed beta-END levels nor [(3)H]-DAMGO binding to mu opioid receptors in any of the regions studied. However, beta-END levels in the sucrose group were significantly increased in the nucleus accumbens and substantia nigra, in comparison to all other groups. These findings suggest that different neural mechanisms and specific brain regions may be involved in the reinforcing effects of ethanol and sucrose.
中脑边缘多巴胺能系统在乙醇的强化效应中发挥着重要作用。阿片肽调节该系统的活性，并被认为至少部分介导了乙醇的强化特性。因此，β-内啡肽（β-END）可能参与了乙醇强化和成瘾的发展。本工作旨在研究急性和慢性乙醇对中脑边缘系统β-END 含量的影响，并探讨慢性乙醇处理是否改变了配体与μ阿片受体（muOR）的结合。雄性 Wistar 大鼠经胃内给予单次急性乙醇剂量 2.5 g/kg 或水。对于慢性乙醇处理实验，一组大鼠给予乙醇（10%v/v 溶液）饮用，两组大鼠分别给予等体积的蔗糖（14.14%等热量溶液）或水，第四组大鼠自由获取食物和水。治疗持续 4 周。通过放射免疫分析定量测定脑区β-END 含量，并用 8 nM[3H]-DAMGO 作为放射性配体通过定量放射自显影研究 muOR 的配体结合。急性乙醇给药 1 小时后，下丘脑β-END 含量降低（26%）。在中脑、腹侧被盖区、黑质、伏隔核、伏隔核-隔区和前额叶皮质中未观察到乙醇的影响。慢性乙醇处理在研究的任何区域均未改变β-END 水平或[3H]-DAMGO 与 mu 阿片受体的结合。然而，与所有其他组相比，蔗糖组的伏隔核和黑质中的β-END 水平显著增加。这些发现表明，不同的神经机制和特定的脑区可能参与了乙醇和蔗糖的强化作用。
