Ide Soichiro, Minami Masabumi, Sora Ichiro, Ikeda Kazutaka
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Methods Mol Biol. 2010;617:363-74. doi: 10.1007/978-1-60327-323-7_27.
Nonselective opioid partial agonists, such as buprenorphine, butorphanol, and pentazocine, have been widely used as analgesics and for anti-addiction therapy. However, the precise molecular mechanisms underlying the therapeutic and rewarding effects of these drugs have not been clearly delineated. Recent success in developing mu-opioid receptor knockout (MOP-KO) mice has elucidated the molecular mechanisms underlying the effects of morphine and other opioids. We have revealed the in vivo roles of MOPs in the effects of opioid partial agonists by using MOP-KO mice for behavioral tests (e.g., several kinds of antinociceptive tests for analgesic effects, conditioned place preference test for dependence). The combination of the cell culture assays using cDNA for mu, delta, and kappa opioid receptors and the behavioral tests using MOP-KO mice has provided novel theories on the molecular mechanisms underlying the effects of opioid ligands, especially opioid partial agonists.
非选择性阿片类部分激动剂，如丁丙诺啡、布托啡诺和喷他佐辛，已被广泛用作镇痛药和用于抗成瘾治疗。然而，这些药物治疗和奖赏作用背后的确切分子机制尚未明确阐明。最近在培育μ-阿片受体敲除（MOP-KO）小鼠方面取得的成功，阐明了吗啡和其他阿片类药物作用背后的分子机制。我们通过使用MOP-KO小鼠进行行为测试（例如，几种用于镇痛作用的抗伤害感受测试、用于依赖性的条件性位置偏爱测试），揭示了MOPs在阿片类部分激动剂作用中的体内作用。使用μ、δ和κ阿片受体的cDNA进行细胞培养分析与使用MOP-KO小鼠进行行为测试相结合，为阿片类配体，尤其是阿片类部分激动剂作用背后的分子机制提供了新的理论。
