Modulation of naloxone-precipitated morphine withdrawal syndromes in rats by neuropeptide FF analogs

Neuropeptide FF (NPFF) has been reported to be an endogenous anti-opioid pe ptide that has significant effects on morphine tolerance and dependence. In the present study, we examined the chronic effects of NPFF and its synthet ic analogs: the putative agonist, PFRFamide, and the putative antagonists, dansyl-PQRamide and PFR(Tic)amide on naloxone-precipitated morphine withdra wal syndromes in rats. After a 5-day co-administration with morphine [5 mg/ kg, intraperitoneally (i.p.), twice per day (b.i.d.)] and the tested peptid e [intracerebroventricularly (i.c.v.) or i.p., b.i.d.], naloxone (4 mg/kg, i.p.) was given systemically to evaluate the severity of the morphine withd rawal syndromes. Our results revealed that NPFF significantly potentiated t he overall morphine withdrawal syndromes and, on the contrary, dansyl-PQRam ide attenuated these syndromes. These results clearly indicate that modulat ion of the NPFF system in the mammalian central nervous system has signific ant effects on opiate dependence. In addition, morphine withdrawal syndrome s could be practically applied as a valid parameter to functionally charact erize the putative NPFF agonists and antagonists. (C) 1999 Elsevier Science Inc. All rights reserved.