Long-term voluntary access to running wheels decreases kappa-opioid antinociception

Previous research has demonstrated that voluntary exercise is associated with a reduction in mu-opioid-induced antinociception. To determine if the effects of voluntary exercise on opioid-induced antinociception were limited to drugs that affect the mu opioid receptor or were more general, the analgesic effects of the kappa opioid agonist U50,488H were compared in active and sedentary rats. Eight adult male Long-Evans rats were housed in standard hanging cages and eight in cages with attached running wheels for 20 days prior to antinociceptive testing. Pain thresholds were determined using a tail-flick procedure, and antinociception was expressed as percent maximal possible effect (%MPE). In the first study, U50,488H was administered in a cumulative dosing procedure (5.0, 10.0, 20.0 mg/kg). Tail-flick latencies were measured immediately prior to and 30 min following each injection. In the second study, the time course of U50,488H effects was examined in animals from the first experiment. Tail-flick latencies were measured immediately prior to and 30, 60, and 90 min following 10.0 mg/kg U50,488H. In the first study, U50,488H produced significant antinociception in both groups of rats. However, antinociceptive responses were significantly reduced for rats given access to running wheels relative to inactive rats. In the second study, antinociceptive responses to U50,488H continued for 90 min. Again, antinociceptive responses were lower for rats given access to running wheels relative to inactive rats. These results indicate that long-term voluntary exercise decreases the antinociceptive properties of the kappa agonist U50,488H, as well as the mu agonist morphine.