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Previous research has demonstrated that chronic intake of nutritive sweet solutions, but not nonnutritive sweet solutions, enhances morphine's analgesic potency. To separate out the effects of sweet taste from other changes in dietary intake, which result when rats consume a sucrose solution, the effects of altering dietary levels of protein, or vitamins and minerals on morphine-induced analgesia were examined. In Experiment 1, 40 male Long-Evans rats were fed standard chow or a semipurified diet containing either 10, 20, or 40% protein. Three weeks later, antinociceptive responses to morphine were examined using the tail flick procedure. Tail flick latencies were measured immediately prior to and 30, 60, and 90 min after the administration of morphine sulfate (0.0, 1.25, 2.5, and 5.0 mg/kg, SC). At all three measurement times, antinociceptive responses increased directly as a function of the dose of morphine, but did not differ as a function of diet. In Experiment 2, 24 rats were maintained on either standard laboratory chow or semipurified diets containing 20% protein and either 100% or 25% of the recommended levels of vitamins and minerals for 3 weeks. Tail flick latencies were measured immediately prior to and 30 min after injections (SC) of 2.5 mg/kg morphine sulfate. This procedure was repeated until a cumulative dose of 10.0 mg/kg was obtained. Tail flick latencies increased significantly as a function of drug dose, but did not differ across dietary conditions. These results demonstrate that the increase in morphine-induced analgesia seen in rats consuming a sucrose solution is not due to alterations in either protein or micronutrient intake.

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.

Previous research has suggested that chronic intake of palatable foods and fluids enhances the activity of the endogenous opioid system. To examine this suggestion, the effect of naltrexone on food intake was examined in male Long-Evans rats with or without prior exposure to palatable solutions. In Experiment 1, rats were fed laboratory chow alone or laboratory chow and a 32% sucrose solution, and in Experiment 2, were fed chow alone, chow and a 32% Polycose solution, or chow and a 0.15% saccharin solution for three weeks. The sucrose, Polycose, and saccharin solutions were removed 18 h prior to drug administration. Rats then received injections of naltrexone hydrochloride (0.0, 0.3 or 3.0 mg/kg. sc) and chow intakes were measured during the subsequent 1, 2, 4, 6 and 24 h. Naltrexone injections had minimal effects on intakes of animals which previously had consumed only chow. In contrast, naltrexone led to significant dose-related decreases in chow intakes in rats which had previously consumed the sucrose, Polycose, or saccharin solutions. These results provide confirmation for the suggestion that chronic intake of palatable solutions alters the activity of the endogenous opioid system.

The effects of intake of a palatable food source on oral amphetamine intake were assessed in adult male Long-Evans rats. In Experiment 1, six rats were given an amphetamine sulfate solution (0.1 mg/ml) and four rats were given water as their sole source of fluid. Rats were given a choice of chow and granulated sucrose for a week, alternated with weeks when only chow was fed. In Experiment 2, eight rats were given the amphetamine solution, and four rats water to drink. Rats were fed chow and hydrogenated vegetable fat for a week alternated with weeks when only chow was available. In both experiments, rats drank significantly less of the amphetamine solution when the palatable food choice was available than when given only chow to eat. Intake of palatable foods had a significantly smaller effect on water intake. In both experiments, rats drinking the amphetamine solution took in less fluid and less calories and gained less weight than rats drinking water. However, in Experiment 1, when sucrose was available, rats drinking amphetamine consumed a significantly greater proportion of their calories as sucrose than rats drinking water. Similarly, in Experiment 2, rats drinking the amphetamine solution chose a significantly greater percentage of their calories as fat than rats drinking water. These results demonstrate that intake of sucrose or fat leads to a significant reduction in amphetamine intake, and that the anorectic effects of amphetamine are not equivalent for different types of foods.