Abstract

The administration of p-chlorophenylalanine (pCPA) inhibited partially the development of tolerance to and physical dependence on morphine induced by morphine pellet implantation in the mouse and rat. Tolerance inhibition by pCPA was evidenced by the decreased amount of morphine necessary to produce analgesia and by the reduction in dependence by the increase in the amount of naloxone necessary to induce precipitated withdrawal jumping after pCPA treatment. Further evidence that pCPA reduced dependence development on morphine was indicated by the fact the pCPA decreased the loss in body weight that occurred after abrupt morphine withdrawal. Regional studies of serotonin turnover in four brain areas indicated that tolerant-dependent mice exhibited higher serotonin levels after pargyline than nontolerant controls, especially in the hypothalamus and brain stem.