The octapeptide FLFQPQRFamide (
neuropeptide FF or F8Fa) may play a role in
opiate dependence and subsequent abstinence syndrome. Previously,
NPFF precipitated
opiate abstinence syndrome, while
IgG from
NPFF antiserum attenuated subsequent
naloxone-precipitated abstinence signs in dependent rats. The
peptide desamino YFLFQPQRamide (
daY8Ra) was synthesized as a possible
NPFF antagonist. At a dose of 600 ng ICV,
daY8Ra significantly attenuated (p less than 0.001) the number of abstinence-like signs subsequently induced by 10 micrograms
NPFF ICV, suggesting that
daY8Ra does have antagonist activity against
NPFF. Pretreatment of
morphine-dependent rats with the same dose of
daY8Ra also significantly attenuated (p less than 0.001) the abstinence signs subsequently precipitated by 10 micrograms
naloxone ICV. Pretreatment with 600 ng of
NPFF itself, or of
NPFF modified at the N-terminal only (daY9Fa), failed to attenuate subsequent
naloxone-precipitated abstinence, suggesting that the C-terminal modification is critical for
NPFF antagonist activity. It should be noted, however, that higher doses of
daY8Ra (2 micrograms or more) can precipitate some abstinence signs in a manner similar to
NPFF.