Department of Psychology, Princeton University, Princeton, NJ 08544, USA.
Alcohol. 2013 Feb;47(1):31-8. doi: 10.1016/j.alcohol.2012.11.001. Epub 2012 Nov 28.
The opioid system is known to enhance motivated behaviors, including ethanol drinking and food ingestion, by acting in various reward-related brain regions, such as the nucleus accumbens, ventral tegmental area and medial hypothalamus. There is indirect evidence, however, suggesting that opioid peptides may act differently in the perifornical lateral hypothalamus (PF/LH), causing a suppression of consummatory behavior. Using brain-cannulated Sprague-Dawley rats trained to voluntarily drink 7% ethanol, the present study tested the hypothesis that opioids in the PF/LH can reduce the consumption of ethanol, with animals receiving PF/LH injections of the δ-opioid receptor agonist D-Ala2-met-enkephalinamide (DALA), the μ-receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO), the κ-receptor agonist (±)-trans-U-50,488 methanesulfonate (U-50,488H), or the general opioid antagonist methylated naloxone (m-naloxone). The consumption of ethanol, lab chow, and water was monitored for 4 h after injection. The results showed that the three opioid receptor agonists injected into the PF/LH specifically and significantly reduced ethanol intake, while causing little change in chow or water intake, and the opposite effect, enhanced ethanol intake, was observed with the opioid antagonist. Of the three opioid agonists, the δ-agonist appears to produce the most consistent and long-lasting suppression of consumption. This effect was not observed with injections 2 mm dorsal to this area, focusing attention on the PF/LH as the main site of action. These results suggest that the opioid peptides have a specific role in the PF/LH of reducing ethanol drinking, which is distinct from their more commonly observed appetitive actions in other brain areas. The additional finding, that m-naloxone in the PF/LH stimulates ethanol intake in contrast to its generally suppressive effect in other regions, focuses attention on this hypothalamic area and its distinctive role in contributing to the variable effects sometimes observed with opioid antagonist therapy for alcoholism.
阿片系统通过作用于各种与奖赏相关的脑区，如伏隔核、腹侧被盖区和内侧下丘脑，已知可增强动机行为，包括乙醇摄入和食物摄入。然而，有间接证据表明，阿片肽在穹窿周外侧下丘脑 (PF/LH) 中的作用可能不同，导致摄取行为受到抑制。本研究使用接受自愿饮用 7%乙醇训练的脑套管 Sprague-Dawley 大鼠，检验了 PF/LH 中的阿片类物质是否可以减少乙醇消耗的假设，动物接受 PF/LH 注射δ-阿片受体激动剂 D-Ala2-met-enkephalinamide (DALA)、μ-受体激动剂 [D-Ala2、N-MePhe4、Gly-ol]-enkephalin (DAMGO)、κ-受体激动剂 (±)-trans-U-50,488 甲磺酸 (U-50,488H) 或一般阿片受体拮抗剂甲基纳洛酮 (m-纳洛酮)。注射后监测 4 小时内乙醇、实验室饲料和水的消耗情况。结果表明，三种阿片受体激动剂注入 PF/LH 可特异性且显著减少乙醇摄入，同时对饲料或水摄入几乎没有影响，而阿片受体拮抗剂则观察到相反的效果，增强了乙醇摄入。在三种阿片类激动剂中，δ-激动剂似乎对消耗的抑制作用最一致且持久。在该区域背侧 2mm 处注射时未观察到这种作用，这使人们将注意力集中在 PF/LH 作为主要作用部位上。这些结果表明，阿片肽在 PF/LH 中具有特定的作用，可减少乙醇摄入，这与它们在其他脑区中更常见的食欲作用不同。额外的发现是，m-纳洛酮在 PF/LH 中刺激乙醇摄入，与它在其他区域的普遍抑制作用形成对比，这使人们将注意力集中在这个下丘脑区域及其在促成阿片受体拮抗剂治疗酒精中毒时有时观察到的可变作用中的独特作用上。
