EFFECTS OF SECRETIN ON ACUTE AND CHRONIC EFFECTS OF MORPHINE

The effects of intracerebroventricularly (ICV) administered secretin o n the analgesic, tolerance-inducing, and dependence-inducing actions o f morphine were investigated, in adult, male CFLP mice. Secretin admin istered doses ICV did not itself affect pain sensitivity in a heat-rad iant tail flick test. However, it depressed the acute nociceptive effe ct of a single subcutaneous (SC) dose of morphine (4 mg/kg) after ICV (1 or 10 ng/ animal) secretin administration. A dose of 10 ng secretin facilitated the development of acute morphine tolerance. On the other hand, none of the doses applied had any influence on chronic morphine tolerance, where animals were implanted SC with a morphine- containin g pellet and the pain sensitivity was measured 3 days later. Morphine withdrawal signs were also evaluated by injecting naloxone. In a 100-n g dose, secretin increased the latency of the withdrawal jumping respo nse; the peptide did not modify the other abstinence signs. These data suggest that central secretin administration can modify the analgesic effect of morphine.