Incomplete, Asymmetric, and Route-Dependent Cross- Tolerance between Oxycodone and Morphine in the Dark

Our previous studies indicate that oxycodone is a putative k-opioid agonist, whereas morphine is a well documented m-opioid agonist. Because there is limited information regard-ing the development of tolerance to oxycodone, this study was designed to 1) document the development of tolerance to the antinociceptive effects of chronically infused i.v. oxycodone relative to that for i.v. morphine and 2) quantify the degree of antinociceptive cross-tolerance between morphine and oxyc-odone in adult male Dark Agouti (DA) rats. Antinociceptive testing was performed using the tail-flick latency test. Com-plete antinociceptive tolerance was achieved in 48 to 84 h after chronic infusion of equi-antinociceptive doses of i.v. oxyc-odone (2.5 mg/24 h and 5 mg/24 h) and i.v. morphine (10 mg/24 h and 20 mg/24 h, respectively). Dose-response curves fo