Abstract Rationale: E-2078 ([N-methyl-Tyr1, N-methyl-

Arg7, D-Leu8] dynorphin A(1–8) ethylamide) is a dynor-phin A(1–8) analog with a reduced tendency to be bio-transformed, when compared to the unmodified opioid peptide. E-2078 has been found to produce k-opioid ago-nist effects in vivo in rodents. Objective: In the present studies, we investigated whether systemically adminis-tered E-2078 could produce k-agonist effects in rhesus monkeys, in tests of antinociception, diuresis and ethyl-ketocyclazocine (EKC) discrimination. Methods: E-2078 (0.32–18 mg/kg, SC, IM or IV) was tested in the warm water (50°, 55°C) tail withdrawal assay of thermal anti-nociception. The diuretic effects of E-2078 (0.056– 1.8 mg/kg, SC) were also compared to those of the k-ag-onist, U69,593 (0.01–0.32 mg/kg, SC). Lastly, the effects of E-2078 (0.1–3.2 mg/kg, SC or IV) were studied in rhesus monkeys trained to discriminate EKC (0.0056 mg/kg SC) from vehicle, in a food-reinforced operant procedure. Results: E-2078 did not produce thermal anti-nociception in rhesus monkeys following SC or IM ad-ministration, up to the largest doses presently studied (i.e., 18 and 10 mg/kg, respectively). E-2078 caused thermal antinociception by the IV route, but this effect was not apparently mediated by k- or µ-opioid receptors, as shown by its insensitivity to quadazocine (1 mg/kg) pretreatment. However, SC E-2078 caused diuresis, and this effect was blocked by quadazocine pretreatment, consistent with mediation by k-opioid receptors. E-2078 generalized in EKC-discriminating monkeys, but only after the largest dose (3.2 mg/kg), and only following IV administration. Conclusions: The present studies suggest that systemically administered E-2078 can produce some k-receptor mediated effects in rhesus monkeys, but its profile of action is not identical to non-peptidic k-ago-nists following all routes of administration, or across all experimental situations. Key words Antinociception · Diuresis · k-Opioid receptors · Macaca mulatt