Tolerance to morphine-induced antinociception is decreased by chronic sucrose or polycose intake.

Chronic intake of palatable fluids alters morphine-induced antinociception. Two experiments were conducted to evaluate how long-term access to palatable fluids alters the development of tolerance to morphine-induced antinociception. In Experiment 1, 40 adult male Long-Evans rats were used. In addition to ad lib chow and water, 10 rats were given a 0.15% saccharin solution, 10 were given a 32% sucrose solution, and 10 were given a 32% Polycose solution to drink for 3 weeks. Ten rats were given chow and water alone, and served as dietary controls. Morphine-induced antinociception was assessed using the radiant-heat tail-flick method (TF). Half of the animals in each dietary condition were given preexposure to 7.5 mg/kg morphine; the other half received saline. All rats were given a TF 30-min postinjection. To determine whether tolerance developed, a cumulative dose paradigm (0.625, 1.25, 2.5, 5.0, 10.0 mg/kg) was employed 1 week after initial morphine injections, and was repeated at weekly intervals for 3 weeks. Antinociception was significantly lower in rats preexposed to morphine relative to rats preexposed to saline. Although all rats displayed decreased antinociception relative to the first morphine injection, rats that drank saccharin showed greater reductions in morphine-induced antinociception relative to rats that drank sucrose or Polycose. Experiment 2 was conducted to determine whether initial pairing of the TF with morphine preexposure produced differences in the development of opioid tolerance. All conditions and procedures were identical to Experiment 1, except that the initial morphine and saline injections were not followed by TF. As in Experiment 1, rats that drank saccharin showed less antinociception than rats that drank sucrose or Polycose. The present results suggest that long-term intake of palatable nutritive solutions curbs tolerance to morphine-induced antinociception, whereas long-term intake of a nonnutritive, sweet saccharin solution does not.