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

Abstract Chronic voluntary exercise in wheels for 5 weeks in spontaneously hypertensive rats (SHR) augments in vivo natural killer (NK) cell cytotoxicity. Endogenous β-endorphin is increased in cerebrospinal fluid after voluntary exercise in rats and we have recently shown that β-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 involvement of central opioid systems in the exercise-induced augmentation in natural immunity. Exercise consisted of voluntary running in wheels for 5 weeks. In vivo cytotoxicity was measured as clearance of injected 51 Cr-labeled YAC-1 lymphoma cells from the lungs. The clearance of YAC-1 cells in vivo was significantly increased in runners as compared to sedentary controls. Selective δ, κ, or μ -opioid receptor antagonists were administered i.c.v. with osmotic minipumps during the last 6 days of the 5 weeks of running. The δ-receptor antagonist naltrindole (40–50 μg day ) significantly but not completely inhibited the enhanced NK-cell cytotoxicity seen after 5 weeks of exercise. Neither the κ-receptor antagonist nor-BNI or the μ-receptor antagonist β-FNA influenced the augmentation in NK cell cytotoxicity. Nor-BNI per se significantly augments in vivo cytotoxicity, indicating some inhibiting effect on natural immunity that could be mediated through the κ-opioid receptor. Our data suggest the involvement of central δ-opioid receptors in the enhancement of natural cytotoxicity seen after chronic voluntary exercise.