Physical dependence produced by chronic intracerebroventricular infusion of [D-Arg]kyotorphin or thiorphan to rats.
Two compounds, [D-Arg]kyotorphin and thiorphan, unique in their mechanisms for producing an opioid-like analgesic response, were infused for six days into the lateral cerebral ventricle of rats. [D-Arg]kyotorphin (62.5 micrograms/microliter per h) and thiorphan (75 micrograms/5 microliter per h), but not vehicle infused animals, displayed certain behaviors characteristic of precipitated morphine withdrawal upon naloxone (10 mg/kg i.p.) challenge. Acute intracerebroventricular (i.c.v.) administration of [D-Arg]kyotorphin (62.5 micrograms/5 microliter) or thiorphan (75 micrograms/5 microliter) and subsequent challenge with naloxone resulted in no abnormal behavior. These data indicate that compounds which produce their analgesic effect through the modulation of endogenous opioids can cause physical dependence.
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects; D004723:Endorphins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D015260:Neprilysin; D009293:Opioid-Related Disorders; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D013375:Substance Withdrawal Syndrome; D015244:Thiorphan; D008625:Tiopronin / Q000031:analogs & derivatives / Q000494:pharmacology*
D000603:Amino Acids, Sulfur; D000700:Analgesics; D004723:Endorphins; D011480:Protease Inhibitors; D011957:Receptors, Opioid; C019448:kyotorphin; D009270:Naloxone; D009020:Morphine; D015244:Thiorphan; D008625:Tiopronin; D015260:Neprilysin