Roberts A J, McDonald J S, Heyser C J, Kieffer B L, Matthes H W, Koob G F, Gold L H
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Pharmacol Exp Ther. 2000 Jun;293(3):1002-8.
Opioid peptides long have been hypothesized to play a role in ethanol reinforcement. Neuropharmacological studies have shown that opioid receptor antagonists decrease ethanol self-administration in rodents and prevent relapse in humans. However, the exact mechanism for such powerful effects has remained elusive. The availability of mu-opioid receptor knockout mice has made possible the direct examination of the role of the mu-opioid receptor in mediating ethanol self-administration. In the present experiments, both nosepoke and lever operant ethanol self-administration and several tests of two bottle-choice ethanol drinking were studied in these genetically engineered mice. In no case did knockout mice show evidence of ethanol self-administration, and, in fact, these mice showed evidence of an aversion to ethanol under several experimental conditions. These data provide new evidence for a critical role for mu-opioid receptors in ethanol self-administration assessed with a variety of behavioral paradigms and new insights into the neuropharmacological basis for ethanol reinforcement.
长期以来，人们一直推测阿片肽在乙醇强化作用中发挥作用。神经药理学研究表明，阿片受体拮抗剂可减少啮齿动物的乙醇自我给药，并防止人类复发。然而，这种强大作用的确切机制仍然难以捉摸。μ-阿片受体基因敲除小鼠的出现，使得直接研究μ-阿片受体在介导乙醇自我给药中的作用成为可能。在本实验中，对这些基因工程小鼠进行了鼻触和杠杆操作性乙醇自我给药研究，以及几项双瓶选择乙醇饮用测试。基因敲除小鼠在任何情况下都没有表现出乙醇自我给药的迹象，事实上，这些小鼠在几种实验条件下都表现出对乙醇的厌恶。这些数据为μ-阿片受体在多种行为范式评估的乙醇自我给药中的关键作用提供了新证据，并为乙醇强化的神经药理学基础提供了新见解。
