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

• Published in: Neuropeptides (Edinburgh) Vol. 44; no. 3; pp. 279 - 283
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.06.2010; Elsevier
• Subjects: Advanced Basic Science; Aminopeptidase; Analgesics; Angiotensin-converting enzyme inhibitors; Animals; Biological and medical sciences; Cysteine proteinase; Cysteine Proteinase Inhibitors - pharmacology; Dipeptides - administration & dosage; Dipeptides - metabolism; Drug dependence; Dynorphin A; Dynorphin B; Dynorphins; Dynorphins - administration & dosage; Dynorphins - metabolism; Endocrinology & Metabolism; endopeptidase; Ethylmaleimide - administration & dosage; Ethylmaleimide - pharmacology; Fundamental and applied biological sciences. Psychology; Injections, Intraventricular; Intracerebroventricular administration; Intracerebroventricular injection; Jumping; Male; Medical sciences; Medicin och hälsovetenskap; Mice; Morphine; Morphine Dependence - physiopathology; Morphine-dependent mouse; N-Ethylmaleimide; Naloxone; Naloxone - pharmacology; Neuropeptides; Neuropharmacology; Pharmacology. Drug treatments; Protease inhibitors; Proteinase inhibitors; Substance Withdrawal Syndrome - physiopathology; Vertebrates: endocrinology; Withdrawal jumping; benzoyl; Intracerebroventricular injection; Protease inhibitors; Boc; Withdrawal jumping; Bz; Dynorphins; tert-butyloxycarbonyl; Morphine-dependent mouse; Morphinan derivatives; Thiol; Cysteine; Rodentia; Opiates; Morphine; Cerebral ventricle; Narcotic analgesic; Neuropeptide; Opioid peptide; Sulfur containing aminoacid; Vertebrata; Mammalia; Naloxone; Mouse; Animal; Dynorphin; Intracerebral administration; Protease inhibitor
• ISSN: 0143-4179; 1532-2785; 1532-2785
• DOI: 10.1016/j.npep.2010.02.001

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 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.