Enhancement of natural immunity seen after voluntary exercise in rats. Role of central opioid receptors

Chronic voluntary exercise in wheels for 5 weeks in spontaneously hypertens ive rats (SHR) augments in vivo natural killer (NK) cell cytotoxicity. Endo genous beta-endorphin is-increased in cerebrospinal fluid after voluntary e xercise in rats and we have recently shown that beta-endorphin administered i.c.v. augments NK cell mediated cytotoxicity in vivo in a similar way as chronic voluntary exercise. We have now further investigated the involvemen t of central opioid systems in the exercise-induced augmentation in natural immunity. Exercise consisted of voluntary running in wheels for 5 weeks. I n vivo cytotoxicity was measured as clearance of injected Cr-51-labeled YAC -I lymphoma cells from the lungs. The clearance of YAC-I cells in vivo was significantly increased in runners as compared to sedentary controls. Selec tive delta, kappa, or mu -opioid receptor antagonists were administered i.c .v. with osmotic minipumps during the last 6 days of the 5 weeks of running . The delta-receptor antagonist naltrindole (40-50 mu g/day) significantly but not completely inhibited the enhanced NK-cell cytotoxicity seen after 5 weeks of exercise. Neither the kappa-receptor antagonist nor-BNI or the mu -receptor antagonist beta-FNA influenced the augmentation in NK cell cytoto xicity. Nor-BNI per se significantly augments in vivo cytotoxicity, indicat ing some inhibiting effect on natural immunity that could be mediated throu gh the kappa-opioid receptor. Our data suggest the involvement of central d elta-opioid receptors in the enhancement of natural cytotoxicity seen after chronic voluntary exercise.