ANALOG OF NEUROPEPTIDE-FF ATTENUATES MORPHINE ABSTINENCE SYNDROME

被引:52
作者
MALIN, DH [1 ]
LAKE, JR [1 ]
LEYVA, JE [1 ]
HAMMOND, MV [1 ]
ROGILLIO, RB [1 ]
ARCANGELI, KR [1 ]
LUDGATE, K [1 ]
MOORE, GM [1 ]
PAYZA, K [1 ]
机构
[1] NICHHD, DEV NEUROBIOL LAB, BETHESDA, MD 20892 USA
关键词
MORPHINE; OPIATE DEPENDENCE; OPIATE ABSTINENCE SYNDROME; F8FAMIDE; NEUROPEPTIDE-FF; MORPHINE-MODULATING PEPTIDE; FMRFAMIDE; ANTIOPIATE PEPTIDES;
D O I
10.1016/0196-9781(91)90052-Q
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 desaminoYFLFQPQRamide (daY8Ra) was synthesized as a possible NPFF antagonist. At a dose of 600 ng ICV, daY8Ra significantly attenuated (p < 0.001) the number of abstinence-like signs subsequently induced by 10-mu-g 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 < 0.001) the abstinence signs subsequently precipitated by 10-mu-g 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-mu-g or more) can precipitate some abstinence signs in a manner similar to NPFF.
引用
收藏
页码:1011 / 1014
页数:4
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