Tolerance and dependence induced by morphine-like pituitary peptides in rats.
An extract from porcine pituitaries containing peptides with opiate-like activity (endorphins) was investigated for possible tolerance/dependence liability in rats. Repeated intraventricular administration of endorphins induced a degree of tolerance similar to that induced by normorphine. Rats made tolerant to morphine by repeated pellet implantation proved cross-tolerant to the pituitary extract as well as to synthetic methionine-enkephalin. Naloxone given to rats, repeatedly pretreated with endorphins, precipitated a withdrawal syndrome strongly resembling that induced in rats treated with normorphine. Withdrawal precipitated in morphine-dependent rats was suppressed by intraventricularly applied endorphins. The results suggest that identical sites and mechanisms are involved in the development of tolerance/dependence induced by opiates and pituitary endorphins.
D000818:Animals; D004347:Drug Interactions; D004361:Drug Tolerance; D006801:Humans; D009021:Morphine Dependence; D009270:Naloxone; D009294:Narcotics; D010455:Peptides / Q000494:pharmacology*; D010902:Pituitary Gland / Q000032:analysis*; D051381:Rats; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders; D014020:Tissue Extracts / Q000494:pharmacology
D009294:Narcotics; D010455:Peptides; D014020:Tissue Extracts; D009270:Naloxone