Suppressive effects by cysteine protease inhibitors on naloxone-precipitated withdrawal jumping in morphine-dependent mice

Tan-No, Koichi; Sato, Tasuku; Shimoda, Masakazu; Nakagawasai, Osamu; Niijima, Fukie; Kawamura, Shunsuke; Furuta, Seiichi; Sato, Takumi; Satoh, Susumu; Silberring, Jerzy; Terenius, Lars; Tadano, Takeshi

doi:10.1016/j.npep.2010.02.001

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Volume 44, Issue 3 , Pages 279-283, June 2010

Suppressive effects by cysteine protease inhibitors on naloxone-precipitated withdrawal jumping in morphine-dependent mice

Koichi Tan-No
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
- Corresponding author. Tel./fax: +81 22 727 0123.
Tasuku Sato
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Masakazu Shimoda
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Osamu Nakagawasai
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Fukie Niijima
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Shunsuke Kawamura
- Educational Center for Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Seiichi Furuta
- Division of Community Health Care, Hokkaido Pharmaceutical University School of Pharmacy, 7-1 Katsuraoka, Otaru 047-0264, Japan
Takumi Sato
- Department of Pharmacology and Pharmacotherapy, Nihon Pharmaceutical University, Kitaadachi-gun, Saitama 362-0806, Japan
Susumu Satoh
- Department of Pharmacology and Pharmacotherapy, Nihon Pharmaceutical University, Kitaadachi-gun, Saitama 362-0806, Japan
Jerzy Silberring
- Department of Biochemistry and Neurobiology, AGH University of Science and Technology, Krakow, Poland
Lars Terenius
- Department of Clinical Neuroscience, Section of Alcohol and Drug Dependence Research, Karolinska Institute, Stockholm S-171 76, Sweden
Takeshi Tadano
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Received 6 August 2009; accepted 4 February 2010. published online 02 March 2010.

Abstract

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 2days (day 1, 30mg/kg; day 2, 60mg/kg). On day 3, naloxone (8mg/kg) was intraperitoneally administered 3h after final injection of morphine (60mg/kg), and the number of jumping was immediately recorded for 20min. Naloxone-precipitated withdrawal jumping was significantly suppressed by the intracerebroventricular administration of N-ethylmaleimide (0.5nmol) and Boc-Tyr-Gly-NHO-Bz (0.4nmol), inhibitors of cysteine proteases involved in dynorphin degradation, 5min before each morphine treatment during the induction phase, with none given on the test day, as well as by dynorphin A (62.5pmol) and dynorphin B (250pmol). 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.