Opioid antagonists and butorphanol dependence

Abstract Butorphanol has been known to act on μ-, δ, and κ-opioid receptors. μ- and possibly δ-receptors are thought to mediate morphine dependence. Relative to morphine, butorphanol has a higher affinity for μ- and δ-receptors. In the present study, β-funaltrexamine (β-FNA) and naltrindole (NTI) (nonequilibrium μ- and δ-antagonist, respectively) were used to precipitate withdrawal in butorphanol-dependent rats. It was found that β-FNA (12, 24, 48, and 100 nM) did not elicit significant withdrawal behaviors, while NTI caused teeth-chattering (100 nM), wet shakes (100 nM), forepaw tremors (24 nM), yawning (48 and 100 nM), ejaculation (24 nM), and urination (100 nM). The present results indicate that δ-opioid receptors may be involved in mediating butorphanol dependence, while the involvement of μ-opioid receptors needs to be further investigated.