Suppressive effects by cysteine protease inhibitors on naloxone-precipitated withdrawal jumping in morphine-dependent mice.
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 3h 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.
Tan-No
Koichi
K
Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. koichi@tohoku-pharm.ac.jp
Sato
Tasuku
T
Shimoda
Masakazu
M
Nakagawasai
Osamu
O
Niijima
Fukie
F
Kawamura
Shunsuke
S
Furuta
Seiichi
S
Sato
Takumi
T
Satoh
Susumu
S
Silberring
Jerzy
J
Terenius
Lars
L
Tadano
Takeshi
T
D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004151:Dipeptides / Q000008:administration & dosage / Q000378:metabolism; D004399:Dynorphins / Q000008:administration & dosage / Q000378:metabolism; D005033:Ethylmaleimide / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D009270:Naloxone; D004399:Dynorphins; D005033:Ethylmaleimide