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

S. S. Negus, S. J. Henriksen, A. Mattox, G. W. Pasternak, P. S. Portoghese, A. E. Takemori, M. B. Weinger, G. F. Koob

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Abstract

Antagonists selective for μ, δ and κ-opioid receptors were evaluated for their effects on responding maintained by i.v. injections of heroin (60.0 μg/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 μ-selective antagonist β- funaltrexamine (β-FNA; 5.0-20.0 mg/kg, s.c.) produced a dose-dependent increase in responding for heroin, with some doses of β-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 μ1-selective antagonist naloxonazine (NXZ; 7.5-30.0 mg/kg, i.v.) and the δ-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 κ-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 μ receptors play an important role in mediating the reinforcing effects of heroin in the rat. δ and μ1 receptors, but not κ receptors, may also be involved.

Original languageEnglish (US)
Pages (from-to)1245-1252
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume265
Issue number3
StatePublished - 1993

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