ABSTRACT
Neuropeptide FF (NPFF) has been shown to exert various antiopiate actions, including precipitation of opiate abstinence syndrome by third ventricle injection in morphine dependent rats. In the present study, dansyl-Pro-Gln-Arg-Phe-amide, a lipophilic analog of NPFF, was injected into morphine dependent rats and appropriate sham controls at a dose of 9 mg/kg s.c. Comparison groups were injected with ethanol/water vehicle alone. The NPFF analog precipitated a vigorous opiate abstinence syndrome in morphine dependent rats, but not in sham controls.
Subject(s)
Morphine/adverse effects , Neuropeptides/pharmacology , Oligopeptides/pharmacology , Substance Withdrawal Syndrome , Amino Acid Sequence , Animals , Injections, Subcutaneous , Male , Molecular Sequence Data , Morphine/antagonists & inhibitors , Morphine Dependence , Rats , Rats, Sprague-DawleyABSTRACT
Previous studies suggest that neuropeptide FF (NPFF) plays a role in opiate dependence and subsequent abstinence syndrome. Endogenous NPFF also appears to play a role in opiate tolerance since third ventricle injection of IgG from NPFF antiserum selectively restores morphine sensitivity in morphine-tolerant rats. The NPFF analog, desamino YFLFQPQRamide (daY8Ra) has previously antagonized behavioral effects of NPFF and has attenuated morphine dependence. The present study assessed whether daY8Ra could similarly attenuate morphine tolerance. Third ventricle (i.c.v.) injection of daY8Ra restored the analgesic response to i.c.v. morphine in morphine-tolerant rats (radiant heat tail flick test). Saline injection failed to produce this effect. In opiate-naive rats, however, the same treatment with daY8Ra did not affect the analgesic response to i.c.v. morphine. Thus, daY8Ra appears to selectively restore morphine sensitivity in opiate-tolerant animals. These results further support the hypothesis that endogenous NPFF contributes to opiate tolerance.
