Chronic Running-Wheel Activity Decreases Sensitivity to Morphine-Induced Analgesia in Male and Female Rats

Abstract

The effects of exercise on morphine-induced analgesia were examined in male and female Long–Evans rats. In Experiment 1, 10 male rats were housed in standard laboratory cages, and 10 in activity wheels for 20 days prior to nociceptive testing. Pain thresholds were assessed using a tail-flick (TF) procedure. Morphine sulfate was administered using a cumulative dosing procedure (2.5, 5.0, 7.5, 10.0, 12.5, and 15.0 mg/kg). TF latencies were measured immediately prior to and 30 min following each injection. In Experiment 2, morphine-induced analgesia was examined in females in an identical manner to that of Experiment 1. Additionally, to determine if the attenuation of morphine-induced analgesia was permanent or reversible, after the initial test nociceptive test, previously active female rats were placed in standard cages, and previously inactive females placed in running wheels for 17 days prior to a second nociceptive test. Baseline TF latencies were significantly shorter in active male rats than in inactive animals. Additionally, both active male and female rats displayed decreased morphine-induced analgesia relative to inactive controls. Moreover, females that had been inactive and then were permitted to run showed a suppression in morphine-induced analgesia relative to presently inactive rats, and to their own nociceptive responses when sedentary. In contrast, morphine-induced analgesia in initially active females who were housed in standard cages during part 2 of Experiment 2 was enhanced relative to their first nociceptive test and to presently active rats. Experiment 3 examined the effects of short-term (24 h) running on antinociception. Baseline TF latencies were shorter in active rats than inactive rats. However, no differences in morphine-induced analgesia were observed as a function of short-term exposure to exercise. Experiment 4 investigated whether differences in body weight contributed to the differences in morphine-induced analgesia between chronically active and inactive animals. %MPEs did not vary among male rats maintained at 100, 85, or 77% of their free-feeding body weight. These results indicate that chronic activity can decrease morphine’s analgesic properties. These effects may be due to crosstolerance between endogenous opioid peptides released during exercise and exogenous opioids.