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.