The effects of chronic opioid administration on analgesia and respiratory response in rhesus monkeys. The animals were studied under baseline conditions, then after receiving two levels of opioid dosing for 4 weeks each, and finally after abstinence. After each treatment course, they were challenged with various doses of morphine, and analgesic and respiratory responses were assessed. This mimics the clinical setting of a patient receiving chronic opioid who is administered morphine in the perioperative period. Analgesic responses were studied as tail withdrawal latency and reported as percentage of maximum possible effect (MPE); ventilator responses were reported as minute ventilation (V_E) and reported as percent of control. The results show development of reversible tolerance to the analgesic effects of opioids (A), but no tolerance development to the respiratory effects (B). Modified from Paronis and Woods. J Pharmacol Exp Ther 1997; 282:355–62.⁶