Tejwani G A, Rattan A K, Koo K L, Matwyshyn G A, Bhargava H N
Department of Pharmacology, College of Medicine, Ohio State University, Columbus 43210-1239.
Pharmacology. 1994 Apr;48(4):216-25. doi: 10.1159/000139183.
Effects were determined of chronic administration and withdrawal of a highly selective kappa-opioid receptor agonist, U-50,488H, on methionine-enkephalin levels in central and peripheral tissues of male Sprague-Dawley rats. Rats were rendered tolerant to and physically dependent on U-50,488H by twice daily injections of 25 mg/kg of this compound for 5 days. Rats deemed abstinent were injected with this drug for 4 days and sacrificed on 5th day. Methionine-enkephalin concentration increased in the hippocampus of U-50,488H-tolerant-dependent rats, whereas in abstinent rats, its level was elevated only in the hypothalamus. Levels of methionine-enkephalin in the pituitary gland of U-50,488H-tolerant-dependent or abstinent rats were unchanged. Among peripheral tissues, methionine-enkephalin concentration decreased in the adrenal gland of U-50,488H-tolerant-dependent rats. In the U-50,488H-abstinent rats, methionine-enkephalin concentration was elevated in the heart. In tissues of morphine- and U-50,488H-tolerant-dependent and abstinent rats methionine-enkephalin concentrations were affected differentially, suggesting inherent differences in mu- and kappa-opiate-mediated tolerance-dependence and abstinence processes.
研究了长期给予和停用一种高选择性κ-阿片受体激动剂U-50,488H对雄性Sprague-Dawley大鼠中枢和外周组织中甲硫氨酸脑啡肽水平的影响。通过每天两次注射25mg/kg该化合物，持续5天，使大鼠对U-50,488H产生耐受性和身体依赖性。将被认为处于戒断状态的大鼠注射该药物4天，并在第5天处死。U-50,488H耐受性依赖大鼠海马体中甲硫氨酸脑啡肽浓度增加，而在戒断大鼠中，其水平仅在下丘脑中升高。U-50,488H耐受性依赖或戒断大鼠垂体中甲硫氨酸脑啡肽水平未发生变化。在外周组织中，U-50,488H耐受性依赖大鼠肾上腺中甲硫氨酸脑啡肽浓度降低。在U-50,488H戒断大鼠中，心脏中甲硫氨酸脑啡肽浓度升高。在吗啡和U-50,488H耐受性依赖及戒断大鼠的组织中，甲硫氨酸脑啡肽浓度受到不同影响，表明μ-和κ-阿片介导的耐受性-依赖性和戒断过程存在内在差异。
