The nociceptin/orphanin FQ receptor antagonist, [Nphe(1)]NC(1-13)NH2, potentiates morphine analgesia

Nociceptin/orphanin FQ (NC) and its receptor (OP4) represent a novel peptid e/receptor system which has been implicated in the regulation of various ce ntral functions, including pain. The aim of the present study was to explor e the involvement of the endogenous NC/OP4 system in the modulation of opio id analgesia using the selective OP4 receptor antagonist [Nphe(1)]NC(1-13)N H2. Experiments were performed in mice exposed to acute as well as chronic treatment with morphine. [Nphe(1)]NC(1-13)NH2, injected i.c.v. at 30 nmol, strongly potentiated the analgesic effect of supraspinal morphine (1 nmol, i.c.v.) while it only slightly increased the antinociceptive activity of mo rphine given systemically (5 mg/kg, s.c.). [Nphe(1)]NC(1-13)NH, (30 nmol, i .c.v.) also potentiated morphine analgesia in mice made tolerant to the opi ate (30 mg/kg/day for 4 days). These findings implicate the endogenous NC s ignaling as a modulator of morphine analgesia and tolerance. NeuroReport 11 :2369-2372 (C) 2000 Lippincott Wilkins.