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

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.