Effect of antagonists selective for mu, delta and kappa opioid receptors on the reinforcing effects of heroin in rats Journal Article


Authors: Negus, S. S.; Henriksen, S. J.; Mattox, A.; Pasternak, G. W.; Portoghese, P. S.; Takemori, A. E.; Weinger, M. B.; Koob, G. F.
Article Title: Effect of antagonists selective for mu, delta and kappa opioid receptors on the reinforcing effects of heroin in rats
Abstract: Antagonists selective for mu, delta and kappa-opioid receptors were evaluated for their effects on responding maintained by i.v. injections of heroin (60.0 mug/kg/injection) in rats during daily 3-hr sessions. Under base-line conditions, rats self-administered 10 to 20 heroin injections during each session, and injections were separated by relatively constant interinjection intervals of about 10 to 20 min. The mu-selective antagonist beta-funaltrexamine (beta-FNA; 5.0-20.0 mg/kg, s.c.) produced a dose-dependent increase in responding for heroin, with some doses of beta-FNA producing an extinction-like pattern of responding. These results were qualitatively similar to the effect obtained by lowering the unit dose per injection of heroin. The mu1-selective antagonist naloxonazine (NXZ; 7.5-30.0 mg/kg, i.v.) and the delta-selective antagonist naltrindole (1.0-17.0 mg/kg) also produced dose-dependent increases in heroin self-administration, but neither naloxonazine nor naltrindole produced extinction-like patterns of responding. The kappa-selective antagonist nor-binaltorphimine (nor-BNI; 5.0-10.0 mg/kg, s.c.) had no effect on heroin self-administration. These results indicate that mu receptors play an important role in mediating the reinforcing effects of heroin in the rat. Delta and mu1 receptors, but not kappa receptors, may also be involved.
Keywords: morphine; naltrindole; beta-funaltrexamine; naloxonazine; binding-sites; agonists; opiate receptors; nor-binaltorphimine; brain membranes; motivational properties
Journal Title: Journal of Pharmacology and Experimental Therapeutics
Volume: 265
Issue: 3
ISSN: 0022-3565
Publisher: American Society for Pharmacology and Experimental Therapeutics  
Date Published: 1993-06-01
Start Page: 1245
End Page: 1252
Language: English
ACCESSION: WOS:A1993LJ01500028
PROVIDER: wos
PUBMED: 8389859
Notes: Article -- Source: Wos
Citation Impact
MSK Authors
  1. Gavril W Pasternak
    414 Pasternak