Involvement of κ-opioid receptors in opioid dependence/withdrawal: studies using butorphanol

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Abstract

The dependence liability of a class of opioid agonist/antagonist analgesics, e.g. pentazocine, butorphanol, and buprenorphine, is widely recognized. However, the relative involvement of μ-, δ-, and κ-opioid receptors mediating physical dependence on these compounds is not completely known. In the present study, butorphanol dependence was produced by continuous intracerebroventricular (i.c.v.) infusion of butorphanol (26 nmol/h) for 3 days in male Sprague-Dawley rats. Nor-binaltorphimine, a long-acting κ-opioid receptor antagonist, and naloxone, a nonspecific antagonist, were administered i.c.v. to precipitate withdrawal in butorphanol-dependent animals, so as to investigate the involvement of central κ-opioid receptors in opioid dependence. ED50 ratios (naloxone/nor-binaltorphimine) for eliciting withdrawal signs were: teeth-chattering (1.25), yawning (2.13), and ejaculation (0.72). Our data indicate that nor-binaltorphimine precipitated withdrawal behaviors similar to those precipitated by naloxone. It appears that central κ-opioid receptors may play a major role in the development of butorphanol dependence in rats.

References (46)

  • N.A. Sharif et al.

    Discrete mapping of brain mu and delta opioid receptors using selective peptides: quantitative autoradiography, species differences and comparison with kappa receptors

    Peptides

    (1989)
  • G. Warhurst et al.

    Influence of morphine tolerance and withdrawal on intestinal salt and water transport in the rat in vivo and in vitro

    Gastroenterology

    (1984)
  • J.H. Woods et al.

    Substitution and primary dependence studies in animals

    Drug Alcohol Depend.

    (1985)
  • E.E. Abdelhamid et al.

    Selective blockage of delta opioid receptors prevents the development of morphine tolerance and dependence in mice

    J. Pharmacol. Exp. Ther.

    (1991)
  • A. Agmo et al.

    Dopamine and sexual behavior in the male rat: a reevaluation

    J. Neural Transm.

    (1989)
  • J. Arnt et al.

    Facilitation of 8-OHDPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI

    Eur. J. Pharmacol.

    (1991)
  • H.H. Berendsen et al.

    Involvement of 5-HT1C receptors in drug-induced penile erections in rats

    Psychopharmacology

    (1990)
  • J. Bläsig et al.

    Developement of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats

    Psychopmacologia

    (1973)
  • G.R. Brown

    Stadol dependence: another case

    J. Am. Med. Assoc.

    (1985)
  • K.J. Chang et al.

    Potent morphiceptin analogs: structure activity relationship and morphine-like activities

    J. Pharmacol. Exp. Ther.

    (1983)
  • A. Cowan et al.

    Direct dependence studies in rats with agents selective for different types of opioid receptor

    J. Pharmacol. Exp. Ther.

    (1988)
  • W.S. Evans et al.

    A case of Stadol dependence

    J. Am. Med. Assoc.

    (1985)
  • D.E. Gmerek et al.

    Kappa opioids in rhesus monkeys. III. Dependence associated with chronic adminstration

    J. Pharmacol. Exp. Ther.

    (1987)
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