ENHANCED SUSCEPTIBILITY OF THE IMMUNE-SYSTEM TO STRESS IN MORPHINE-TOLERANT RATS

The purpose of the present study was to determine the potential conseq uences to the immune system of the combined exposure of rats to stress or and morphine. Within 30 min following either morphine (5 mg/kg) inj ection or restraint stress (30 min) maximal analgesic responses as mea sured by tail-flick assay were observed. However, only morphine treatm ent was accompanied by a significant suppression (50%) in mitogen-stim ulated lymphocyte proliferative responses. Restraint stress for either a 30-min or 2-h duration had no effect on lymphocyte responses. Expos ure to a combination of restraint stress and acute morphine (5 mg/kg) resulted in a 50% suppression of lymphocyte responses which was simila r in magnitude to that observed with morphine administration alone. Wh en rats were injected twice daily for 4 days with increasing doses of morphine ranging from 10 mg/kg to 40 mg/kg, morphine (10 mg/kg) admini stration on Day 5 was not accompanied by either analgesia or depressed blood lymphocyte proliferative responses. These results indicated tha t tolerance had developed to both the analgesic and the immunosuppress ive effects of morphine. However, upon exposure of morphine-tolerant a nimals to restraint stress, significant analgesic responses were retai ned. Furthermore, in contrast to the lack of suppression following res traint stress on lymphocyte responses in saline-injected animals, rest raint for 30 min produced greater than a 70% suppression in morphine-t olerant animals. These data suggest that morphine tolerance may be acc ompanied by an enhanced susceptibility to the immunosuppressive effect s of stress. (C) 1944 Academic Press, Inc.