Activity-induced anorexia in rats augments the development of tolerance to morphine

Restricting food intake (FI) to 1 h/day for rats housed in running wheels can serve as a model for the excessive exercise often observed in individuals with anorexia nervosa. When maintained on this schedule for several days, rats decrease food intake, increase running and can die of starvation. Studies have shown that freely fed rats allowed to run for 3 weeks become tolerant to morphine's pain-relieving actions. To determine if restricting FI in active rats would produce more rapid development of tolerance, active rats were fed for 24 or 1.5 h/day. When active food-restricted rats reached 75% of their free-feeding body weight, testing for morphine-induced antinociception (MIA) began. Ad lib-fed active rats, were tested for MIA after 3 weeks, or after the amount of time taken for food-restricted active rats to reach their target weight. Inactive rats were given ad lib food or pair-fed the amount of food consumed by active food-restricted rats, and tested for MIA after 3 weeks (ad lib fed) or 6 days (pair-fed). Food-restricted active rats increased running, decreased FI and by day 6, reached 75% of their free-feeding weight and were less sensitive to morphine's pain-relieving actions than rats in any of the inactive groups or active rats given free access to food and tested at the same time as the food-restricted rats. Increasing activity in food-restricted individuals may augment stimulation of endogenous opioid peptides, and thus accentuate the development of tolerance to opiate drugs.