phosphoramidon and Substance-Withdrawal-Syndrome

Topics: Animals; Cerebral Cortex; Dose-Response Relationship, Drug; Electroencephalography; Electroshock; Enkephalins; Glycopeptides; Leucine; Male; Mice; Mice, Inbred Strains; Neprilysin; Nitrous Oxide; Rats; Rats, Inbred Strains; Sleep Deprivation; Sleep, REM; Substance Withdrawal Syndrome; Thiorphan

Enkephalinase inhibitors phosphoramidon, thiorphan or phelorphan suppressed naloxone-precipitated withdrawal symptoms in acute and chronic morphine dependent mice and rats. It is suggested that decreased biotransformation of the endogenous opioid peptides might compensate the relative shortage of exogenous opiates during withdrawal in opiate dependent subjects and could be a new and promising way to attenuate the severity of abstinential syndrome.

Topics: Amino Acids, Sulfur; Animals; Cerebral Ventricles; Cerebrospinal Fluid; Dipeptides; Glycopeptides; Male; Metalloendopeptidases; Mice; Mice, Inbred Strains; Morphine Dependence; Naloxone; Neprilysin; Rats; Rats, Inbred Strains; Stereotyped Behavior; Substance Withdrawal Syndrome; Thiorphan; Tiopronin

The effect of the enkephalinase inhibitor phosphoramidon on the withdrawal syndrome following acute and chronic morphine-induced physical dependence in mice, was investigated. Phosphoramidon administered intracerebroventricularly (50-200 micrograms) suppressed significantly the naloxone-precipitated withdrawal jumping and wet dog shakes while forelimb shakes were potentiated in both acute and chronic morphine-dependent mice. It is suggested that increased saturation of the opioid receptors by endogenous opioid peptides following enkephalinase inhibition, might suppress the severity of the withdrawal syndrome.

Topics: Animals; Behavior, Animal; Endopeptidases; Glycopeptides; Injections, Intraventricular; Male; Mice; Mice, Inbred Strains; Morphine Dependence; Naloxone; Neprilysin; Protease Inhibitors; Substance Withdrawal Syndrome

Intraventricular administration of enkephalinase inhibitor, phosphoramidon (1 X 10(-8)-5.6 X 10(-7) moles ICV) induced a behavioural syndrome consisting of excessive grooming with the body scratching as the most prominent symptom and wet-dog-shakes (WDS). The frequency of the phosphoramidon-induced WDS and body scratching were decreased by the pretreatment with the opiate receptor blocking agent, naltrexone (2.9 X 10(-6) moles/kg IP). Both the phosphoramidon-induced WDS in naive rats and naloxone-precipitated withdrawal WDS were decreased in REM sleep deprived rats compared with animals allowed normal sleep (control and stress groups). The results are discussed in light of a possible functional insufficiency of endorphinergic system during REMSD. It has been suggested that this insufficiency might be a background to the increased neuronal excitability during REMSD.

Topics: Animals; Anti-Bacterial Agents; Glycopeptides; Grooming; Injections, Intraventricular; Male; Naltrexone; Narcotics; Neprilysin; Protease Inhibitors; Rats; Rats, Inbred Strains; Sleep Deprivation; Sleep, REM; Substance Withdrawal Syndrome; Substance-Related Disorders