Development of tolerance to endogenous opiates activated by 24-h food deprivation

Four experiments assessed the effects of exposure to 24-h food deprivation on the tail-flick latency of rats exposed to a temperature stimulus. Confirming previous studies, Experiment 1 showed that food deprivation gave rise to analgesia, as indicated by increased tail-flick latencies, that was antagonized by naloxone. Experiment 2 found that analgesia was greatly reduced after five exposures to periods of 24-h food deprivation (alternating with 24-h free access to food), indicating the development of tolerance. Experiments 3 and 3a examined the development of tolerance to the analgesic effects of morphine following repeated morphine injections, saline injections, and exposure to 24-h food deprivation plus saline injections. The combined results of both experiments provided evidence that repeated exposures to either morphine or food deprivation, produced greater tolerance to morphine than did exposures to saline. That food deprivation was cross-tolerant with morphine indicated that tolerance to food deprivation-induced analgesia involved opioid mechanisms. The relevance of opioid tolerance to psychobiological models of feeding and to the development of an animal model of anorexia nervosa was discussed.