Effect of ethanol on hypothalamic opioid peptides, enkephalin, and dynorphin: Relationship with circulating triglycerides
Effect of ethanol on hypothalamic opioid peptides, enkephalin, and dynorphin: Relationship with circulating triglycerides
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DOI：
10.1111/j.1530-0277.2006.00312.x
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发表时间：
2007-02-01
影响因子：
3.2
通讯作者：
Leibowitz, Sarah F.
中科院分区：
文献类型：
--
作者：
Chang, Guo-Qing;Karatayev, Olga;Leibowitz, Sarah F.
背景：最近的证据表明，乙醇摄入可以刺激下丘脑室旁核（PVN）中摄食刺激肽甘丙肽（GAL）的表达和产生，而PVN注射这种肽反过来又可以增加乙醇的消耗。为了检验其他喂养相关系统参与乙醇摄入的假设，本研究检测了乙醇对下丘脑阿片肽、脑啡肽 (ENK) 和强啡肽 (DYN) 的影响。方法：训练成年雄性 Sprague-Dawley 大鼠在 12 小时的摄入计划中自愿饮用浓度不断增加的乙醇（高达 9% v/v），或者单次注射乙醇（10% v/v）盐水车。使用实时定量聚合酶链反应和放射性标记原位杂交测量乙醇对 GAL、ENK 和 DYN mRNA 的影响，同时使用放射免疫分析法测量肽水平。除血液酒精外，还测量了甘油三酯（TG）、瘦素和胰岛素的循环水平。 结果：数据表明：（1）自愿饮用9% v/v乙醇（约2.0 g/kg/d）的大鼠与饮水大鼠相比，PVN中GAL、ENK和DYN mRNA显着增加； (2) 自愿消耗乙醇也会增加PVN中ENK和DYN的肽水平； (3)急性注射10%乙醇(1.0 g/kg 10% v/v)同样增加PVN中GAL、ENK和DYN的表达； (4) 摄入和注射乙醇虽然对瘦素和胰岛素影响不大，但会持续增加 TG 和酒精的循环水平，这两者都与 PVN 中的肽表达呈强烈正相关。结论：这些发现与已发表的研究一起表明下丘脑阿片肽在饮酒中可能发挥作用。基于膳食脂肪和脂质注射刺激 PVN 肽以及注射阿片类药物和 GAL 增加乙醇摄入量的证据，提出循环中的 TG 和酒精因摄入或注射乙醇而升高，参与刺激 PVN 中的这些肽，进而促进乙醇的进一步消耗。
Background: Recent evidence has demonstrated that ethanol intake can stimulate the expression and production of the feeding-stimulatory peptide, galanin (GAL), in the hypothalamic paraventricular nucleus (PVN), and that PVN injection of this peptide, in turn, can increase the consumption of ethanol. To test the hypothesis that other feeding-related systems are involved in ethanol intake, this study examined the effect of ethanol on the hypothalamic opioid peptides, enkephalin (ENK), and dynorphin (DYN).Method: Adult, male Sprague-Dawley rats were trained to voluntarily drink increasing concentrations of ethanol, up to 9% v/v, on a 12-hour access schedule or were given a single injection of ethanol (10% v/v) versus saline vehicle. The effect of ethanol on GAL, ENK, and DYN mRNA was measured using real-time quantitative polymerase chain reaction and radiolabeled in situ hybridization, while radioimmunoassay was used to measure peptide levels. In addition to blood alcohol, circulating levels of triglycerides (TG), leptin, and insulin were also measured.Results: The data demonstrated that: (1) rats voluntarily drinking 9% v/v ethanol (approximately 2.0 g/kg/d) show a significant increase in GAL, ENK, and DYN mRNA in the PVN compared with water-drinking rats; (2) voluntary consumption of ethanol also increases peptide levels of ENK and DYN in the PVN; (3) acute injection of 10% ethanol (1.0 g/kg of 10% v/v) similarly increases the expression of GAL, ENK, and DYN in the PVN; and (4) ethanol consumption and injection, while having little effect on leptin and insulin, consistently increase circulating levels of TG as well as alcohol, both of which are strongly, positively correlated with peptide expression in the PVN.Conclusions: These findings, together with published studies, suggest a possible role for hypothalamic opioid peptides in the drinking of ethanol. Based on evidence that dietary fat and lipid injections stimulate the PVN peptides and injection of the opiates and GAL increase ethanol intake, it is proposed that both TG and alcohol in the circulation, which are elevated by the ingestion or injection of ethanol, are involved in stimulating these peptides in the PVN, which in turn promote further consumption of ethanol.