期刊
NEUROPEPTIDES
卷 44, 期 3, 页码 279-283出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.npep.2010.02.001
关键词
Protease inhibitors; Dynorphins; Withdrawal jumping; Intracerebroventricular injection; Morphine-dependent mouse
资金
- Japan Society for the Promotion of Science [18613016, 21600012]
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Polish Ministry for Science and Higher Education [3048/B/H03/2009/37]
- Grants-in-Aid for Scientific Research [21600012, 22600010] Funding Source: KAKEN
The effects of various protease inhibitors on naloxone-precipitated withdrawal jumping were examined in morphine-dependent mice. The doses of morphine were subcutaneously given twice daily for 2 days (day 1, 30 mg/kg; day 2, 60 mg/kg). On day 3, naloxone (8 mg/kg) was intraperitoneally administered 3 h after final injection of morphine (60 mg/kg), and the number of jumping was immediately recorded for 20 min. Naloxone-precipitated withdrawal jumping was significantly suppressed by the intracerebroventricular administration of N-ethylmaleimide (0.5 nmol) and Boc-Tyr-Gly-NHO-Bz (0.4 nmol), inhibitors of cysteine proteases involved in dynorphin degradation, 5 min before each morphine treatment during the induction phase, with none given on the test day, as well as by dynorphin A (62.5 pmol) and dynorphin B (250 pmol). However, amastatin, an aminopeptidase inhibitor, phosphoramidon, an endopeptidase 24.11 inhibitor, and captopril, an angiotensin-converting enzyme inhibitor, caused no changes. The present results suggest that cysteine protease inhibitors suppress naloxone-precipitated withdrawal jumping in morphine-dependent mice, presumably through the inhibition of dynorphin degradation. (C) 2010 Elsevier Ltd. All rights reserved.
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