Sensitivity to the effects of a kappa opioid in rats with free access to exercise wheels: differential effects across behavioral measures

It is well established that chronic exercise decreases sensitivity to mu opioid agonists; however, it is less clear what effects it has on kappa opioids. The purpose of the present study was to examine sensitivity to the effects of the selective, kappa opioid spiradoline in rats with free access to exercise wheels. Rats were obtained at weaning and randomly assigned to either standard polycarbonate cages (sedentary) or modified cages equipped with exercise wheels (exercise). After approximately 7 weeks under these conditions, sensitivity to the effects of spiradoline on tests of antinociception, locomotor activity, conditioned place preference, and diuresis were examined in both groups of rats. Sedentary rats were more sensitive than exercising rats to the antinociceptive effects of spiradoline, and this effect was observed at both low and high nociceptive intensities. In contrast, exercising rats were more sensitive than sedentary rats to the diuretic effects of spiradoline, and slightly more sensitive to spiradoline's effects in the conditioned place preference procedure. No differences in sensitivity were observed to the effects of spiradoline on locomotor activity. Sensitivity to the antinociceptive effects of spiradoline nonsignificantly increased in exercising rats that were reassigned to sedentary housing conditions, and changes in spiradoline sensitivity were correlated with exercise output in individual subjects. Collectively, these data suggest that exercise alters sensitivity to the behavioral effects of kappa opioids, but that the direction and magnitude of this effect depends on the behavioral measure examined.