EFFECTS OF CYCLIC 3', 5'-ADENOSINE MONOPHOSPHATE ON MORPHINE TOLERANCE AND PHYSICAL DEPENDENCE

¹ Department of Pharmacology, University of California, San Francisco, California, and Langley Porter Neuropsychiatric Institute, San Francisco, California

The administration of cyclic 3', 5'-adenosine monophosphate (cAMP) antagonized the analgetic response of morphine in both nontolerant and tolerant mice and also accelerated the development of tolerance to and physical dependence on morphine induced by morphine pellet implantation. Tolerance enhancement by cAMP was evidenced by the increased amount of morphine to produce analgesia and acceleration in dependence by the decrease in the amount of naloxone to induce precipitated withdrawal jumping after cAMP pretreatment. Further evidence that cAMP accelerated dependence development on morphine was evidenced by the fact that cAMP increased the loss in body weight that occurred after abrupt morphine withdrawal. Cycloheximide prevented the accelerating effect of cAMP on tolerance and physical dependence development.