Inquiry into endorphinergic feedback mechanisms during the development of opiate tolerance/dependence.

Met-enkephalin and beta-endorphin levels were determined in the pituitary and brain of rats after treatment for several weeks with either agonists of high receptor affinity, such as levorphanol and etorphine, or with the narcotic antagnoist naloxone. Long-term activation of opiate receptors failed to change the endorphin levels in restricted areas of brain and pituitary, although a high degree of tolerance/dependence is apparent in those animals. Chronic blockade of opiate receptors by naloxone also fails to affect endorphin levels in the pituitary, but selectively increases metenkephalin levels in the striatum. The present data do not support the notion of negative feedback mechanisms to regulate endorphingergic functions during the development of opiate tolerance/dependence.