Suppression of food deprivation-induced high-rate wheel running in rats

To test for involvement of endogenous opioids in the maintenance of high-rate running we have administered naloxone, a specific opioid antagonist, to rats. The animals were stabilized voluntarily running 6000 to 8000 m/day through a standard protocol and maintained in this state on approximately 18 g of food per day. Naloxone (50 mg/kg in saline) or saline alone was injected intraperitoneally on alternate days for 20 days. All rats ran less on days when naloxone was administered. The mean distance run for the group (N = 6, mean +/- SE) was: saline: 6401 +/- 985; naloxone: 5344 +/- 805 m/day. This difference was highly significant (p less than 0.001). In the 4-hour period immediately following the naloxone injection there was no inhibition of running. The second four-hour period showed a nonsignificant (p greater than 0.05) decrease in running. Inhibition of running was highly significant after eight hours (30%, p less than 0.001). The results demonstrate a clear inhibition of the high-rate running by naloxone and imply a significant role by endogenous opioids in the maintenance of running. The time course of the inhibition is consistent with the relatively high initial concentrations of naloxone exerting an agonist action and the subsequent lower levels having an antagonist effect.