The Effect of Swim Stress on Morphine Tolerance Development and the Possible Role of Nitric Oxide in this Process

It has been shown that stress and chronic pain could prevent the development of tolerance tomorphine analgesia, which appears to be related to the activation of hypothalamus-pitutitaryadrenal(hpa) axis, activation of neuroendocrine systems and changes in neurochemical levels.moreover, the involvement of nitric oxide (no) in the development of tolerance to morphineanalgesia has been implicated. in the present study, we have tried to investigate the effect ofswim stress, as a painless kind of stress, on the development of tolerance to find out whether theinhibition of tolerance is mediated by the direct effect ofpain on the pain conduction pathway, orby its stress aspect. besides, we evaluated the probable interactions between swim stress, nitricoxide level and the development of morphine tolerance. adult male wistar rats, weighing 180220g, were used in all these experiments. the experimental groups received chronic morphine(20 mg/kg, i.p), swim stress in 200e water bath (4 min), or a combination of swim stress andchronic morphine (20 mg/kg, i.p), each for 4 days, while the first control group received saline(i ml/kg, i.p) for 4 days. on the 5th day, all the experimental and control groups received asingle dose of morphine (10 mg/kg i.p). the second control group received saline for 5 days.the intact group received only one single dose of morphine (10 mg/kg, i.p). all the mentionedgroups were subjected to tail-flick and formalin tests on the 5th day. other experimental groupswere subjected to the assay for measuring nitrite as an indicator ofno, using the griess method.our results showed that co-administration of swim stress with chronic morphine prevented thedevelopment of morphine tolerance and the level ofno increased in the presence of swim stress(p(less than)0001). the combination of morphine and swim stress significantly decreased no productionin comparison with the chronic morphine administered group (p(less than)o.ool). these data suggest thatthe activation of hpa axis and consequently the suppression of (no) production induced bychronic morphine, lead to the inhibition of morphine tolerance