RESUMO
The endogenous neuropeptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-amide) has been shown to counteract various opiate actions. In the current study, third ventricular injection of 35 micrograms Tyr-MIF-1 protected by the enzyme inhibitor bestatin precipitated an abstinence syndrome in morphine-dependent rats, but not in opiate-naive rats. The results raise the possibility that Tyr-MIF-1 might participate in opiate dependence and opiate abstinence syndrome.
Assuntos
Hormônio Inibidor da Liberação de MSH/análogos & derivados , Dependência de Morfina , Morfina/antagonistas & inibidores , Síndrome de Abstinência a Substâncias/etiologia , Animais , Humanos , Recém-Nascido , Hormônio Inibidor da Liberação de MSH/farmacologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
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.
Assuntos
Ventrículos Cerebrais/fisiologia , Dependência de Morfina/fisiopatologia , Oligopeptídeos/farmacologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Sequência de Aminoácidos , Animais , Ventrículos Cerebrais/efeitos dos fármacos , Ventrículos Cerebrais/fisiopatologia , Injeções Intraventriculares , Masculino , Dados de Sequência Molecular , Morfina/farmacologia , Naloxona/farmacologia , Oligopeptídeos/administração & dosagem , Oligopeptídeos/síntese química , Ratos , Ratos Endogâmicos , Síndrome de Abstinência a Substâncias/prevenção & controleRESUMO
Yang et al. (14) have isolated from mammalian brain an octapeptide FLFQPQRF-NH2 (F-8-F-NH2) with certain antiopiate properties. Third ventricular injection of 2 micrograms of this peptide together with the aminopeptidase inhibitor bestatin precipitated an opiate-withdrawal syndrome in morphine-dependent but not in nondependent rats. Third ventricular injection in nondependent rats of 15 micrograms of the peptide together with bestatin induced a morphine-withdrawal-like behavioral syndrome. This syndrome was not produced by injection of bestatin or saline vehicle alone and was preventable by injection of 3.5 mg/kg morphine sulphate SC.
