Neuropeptide FF (
NPFF) has been reported to be an endogenous anti-
opioid peptide that has significant effects on
morphine tolerance and dependence. In the present study, we examined the chronic effects of
NPFF and its synthetic analogs: the putative agonist,
PFRFamide, and the putative antagonists,
dansyl-PQRamide and
PFR(Tic)amide on
naloxone-precipitated
morphine withdrawal 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
peptide [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 withdrawal syndromes. Our results revealed that
NPFF significantly potentiated the overall
morphine withdrawal syndromes and, on the contrary,
dansyl-PQRamide attenuated these syndromes. These results clearly indicate that modulation of the
NPFF system in the mammalian central nervous system has significant effects on
opiate dependence. In addition,
morphine withdrawal syndromes could be practically applied as a valid parameter to functionally characterize the putative
NPFF agonists and antagonists.