Nocistatin, a peptide reversing acute and chronic morphine tolerance

It has been reported that intracerebroventricular (i.c.v.) injection of noc iception/orphanin FQ (OFQ) can antagonize morphine analgesia, whereas i.c.v . OFQ antibody can reverse morphine tolerance. Nocistatin (NST) is a recent ly characterized neuropeptide possessing an antagonizing effect on OFQ. Her e we examine whether i.c.v. NST would result in a reversal of morphine tole rance. The results showed that: (1) i.c.v. NST at doses of 0.005, 0.05, 0.5 , 5 or 50 ng per rat produced a bell-shaped dose-dependent reversal of chro nic morphine tolerance, with maximum response at 0.5 ng. (2) Acute morphine tolerance could also be reversed, albeit partially, by i.c.v. NST at 0.5ng . (3) The reversal of acute and chronic morphine tolerance by NST was compl etely abolished when NST(0.5 ng) was co-injected with (8 mug) OFQ. Since OF Q and NST are derived from the same preprohormone, the profile of its splic ing in the CNS may play an important role in determining the effectiveness of morphine analgesia. NeuroReport 12:1789-1792 (C) 2001 Lippincott William s & Wilkins.