Inhibition of enkephalinase activity attenuates naloxone-precipitated withdrawal symptoms.
In this study we examined the effects of the enkephalinase inhibitor, thiorphan, on the naloxone-precipitated withdrawal syndrome in chronic morphine dependent rats. Intracerebroventricular administration of thiorphan (40 micrograms/2 microliter) in morphine dependent rats, inhibited the severity of the naloxone-precipitated abstinential syndrome. Administration of thiorphan (20 micrograms/0.5 microliter) in the periaqueductal grey matter of morphine dependent rats, in addition to explosive motor behaviour and ipsilateral rotation, also significantly suppressed most of the naloxone-precipitated withdrawal symptoms. It is suggested that a decreased biotransformation of endogenous opioid peptides might replace the relative shortage of morphine during withdrawal in opiate addicted subjects and attenuate the abstinence symptoms.
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D010450:Endopeptidases / Q000378:metabolism; D007267:Injections; D007276:Injections, Intraventricular; D008297:Male; D009021:Morphine Dependence / Q000503:physiopathology; D009270:Naloxone / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D015260:Neprilysin; D010487:Periaqueductal Gray; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000517:prevention & control*; D015244:Thiorphan; D008625:Tiopronin / Q000031:analogs & derivatives / Q000494:pharmacology*
D000603:Amino Acids, Sulfur; D011480:Protease Inhibitors; D009270:Naloxone; D015244:Thiorphan; D008625:Tiopronin; D010450:Endopeptidases; D015260:Neprilysin