Effects of nor-binaltorphimine on the development of analgesic tolerance to and physical dependence on morphine.

Abstract:

:The effects of a highly selective kappa antagonist, nor-binaltorphimine (nor-BNI), on the development of tolerance to morphine analgesia and physical dependence on morphine were examined. Pretreatment with nor-BNI (5 mg/kg s.c.) 2 h prior to injection of morphine or a selective kappa agonist, U-50,488H, significantly antagonized the analgesic effect of U-50,488H, but not morphine analgesia in mice. The development of tolerance to morphine analgesia was significantly potentiated by pretreatment of mice with nor-BNI 2 h prior to morphine treatment during chronic morphine treatment for 5 days. Additionally, the pretreatment with nor-BNI during chronic treatment with the high dose of morphine for 5 days significantly potentiated the naloxone-induced body weight loss in morphine-dependent mice and rats. These findings suggest that inactivation of the kappa opioid system may potentiate the development of tolerance to morphine analgesia in mice and may aggravate the naloxone-precipitated body weight loss in morphine-dependent mice and rats.

journal_name

Eur J Pharmacol

authors

Suzuki T,Narita M,Takahashi Y,Misawa M,Nagase H

doi

10.1016/0014-2999(92)90237-x

keywords:

subject

Has Abstract

pub_date

1992-03-17 00:00:00

pages

91-7

issue

1

eissn

0014-2999

issn

1879-0712

pii

0014-2999(92)90237-X

journal_volume

213

pub_type

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