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.